Investigating the Propagating effects of Griseofulvin on Erectile Dysfunction: A Comprehensive Computational and Molecular Docking Study on Human Phosphodiesterase 5 proteins (1UDT and 1UDU).

Investigating the Propagating effects of Griseofulvin on Erectile Dysfunction: A Comprehensive Computational and Molecular Docking Study on Human Phosphodiesterase 5 proteins (1UDT and 1UDU). | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Investigating the Propagating effects of Griseofulvin on Erectile Dysfunction: A Comprehensive Computational and Molecular Docking Study on Human Phosphodiesterase 5 proteins (1UDT and 1UDU). John Shinggu, Emmanuel Etim, Samuel Humphrey, Bulus Bako This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4492213/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Erectile dysfunction (ED) is a prevalent condition affecting a significant portion of the male population. This research delves into the potential link between Griseofulvin, a known antifungal medication, and its impact on erectile function. A comprehensive computational approach was employed. Optimization of griseofulvin was carried out using the highly reputable density functional theory (DFT) with the B3LYP functional and 6–31*G(d,p) using water and ethanol as the solvents of interest. We explored the interactions of Griseofulvin with Human Phosphodiesterase 5 proteins (PDE5), specifically targeting the crystal structures 1UDT and 1UDU. Molecular docking studies provided valuable insights into the binding mechanisms of Griseofulvin with PDE5, shedding light on potential allosteric modulation and conformational changes. Further molecular docking studies were carried out on other popular antifungal drugs like amphotericin, terbinafine and ketoconazole in order to compare their interactions with 1UDT and 1UDU with that of griseofulvin. Through an array of computational analyses, including molecular dynamics simulations and binding free energy calculations, we aimed to elucidate the propagating effects of Griseofulvin on the catalytic activity and structural stability of PDE5. The findings from this research could contribute to a deeper understanding of the molecular mechanisms underlying Griseofulvin's impact on erectile function, potentially opening avenues for the development of novel therapeutic interventions for ED. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 1.0 Introduction A naturally occurring substance with a variety of biological functions, including antibacterial and antifungal qualities, griseofulvin is obtained from the Penicillium notatum fungus. But little has been discovered about how it might affect erectile function. Antifungal medications are used to treat and prevent fungal infections, which can damage the skin, nails, hair, and internal organs, among other parts of the body [ 1 ]. These medicines, also referred to as antimycotic drugs, function by either eliminating the fungus or stopping it from proliferating. The class of pharmaceuticals known as antifungal drugs is intended to treat fungal infections by either preventing the growth of the fungus causing the infection or by eliminating it entirely [ 2 ]. A fungal infection can impact the skin, nails, respiratory system, and internal organs, among other sections of the body. Effective management of these infections has been made possible by the introduction of antifungal medications. There are many different kinds of antifungal medications, including creams, gels, ointments, sprays, pills, capsules, liquids, and injections. They are used to treat a variety of fungal illnesses, such as severe dandruff, athlete's foot, ringworm, and fungal nail infections in the vagina. Aspergillosis (lung infection), fungal meningitis (brain infection), and candidemia (bloodstream infection) are more severe fungal diseases that need to be treated in a hospital. However, there is an increasing risk to global health due to the development of antifungal resistance [ 3 ]. Antifungal medication resistance in fungi can significantly reduce the range of available treatments. Fungi exposed to antifungal medications may naturally develop resistance or resistance may evolve over time [ 4 ]. Typical antifungal drugs include the Canesten (clotrimazole), benzazole, moxizole, lamisil, terbinafine, diflucan or fluconazole, daktarin or ketoconazole, nystan or nystatin, amphetidine. Fulcin, also known as griseofulvin as shown in Fig. 1 , is an oral antifungal drug used to treat a variety of dermatophytoses that has a long history of safety and effectiveness. It has been a significant therapy option for fungal infections for more than 40 years and is processed in the liver [ 5 ]. The impact of griseofulvin on erectile function, however, is not well understood. Only one (0.51%) of the 196 participants in a phase IV clinical study using FDA data reported experiencing impotence as a side effect while using griseofulvin [ 6 ]. A thorough computational and molecular docking investigation is carried out to see whether griseofulvin has any possible effects on erectile function. The design and synthesis of derivatives of griseofulvin, their molecular docking studies to predict their binding affinity and specificity for target proteins involved in erectile function, and a biological evaluation of the chosen derivatives for their effects on erectile function in vitro and in vivo models could all be part of this study. Additionally, the study looks into the underlying molecular mechanisms of how griseofulvin and its derivatives affect erectile function. 1.1 Nature and Classification of Griseofulvin Once antifungal creams have failed, griseofulvin, an antifungal drug, is used to treat a variety of dermatophytoses, including fungal infections of the skin, scalp, and nails. As a tubulin-inhibiting agent, it works by reducing mitosis to provide its physiological impact. Mycotoxic Griseofulvin is an antifungal polyketide metabolite mostly produced by ascomycetes and a byproduct of Penicillium species metabolism [ 7 – 10 ]. Since the drug is useless when applied topically, it must be taken orally and is only useful for dermatophytosis. Griseofulvin is a suspension that can be taken orally and has a well-established track record of safety and effectiveness. Sometimes dosage changes are required because of the liver's role in its metabolism. With a lengthy history of safety and effectiveness, griseofulvin is a tubulin-inhibiting agent that is mostly used to treat dermatophytoses. Because it is inefficient when used topically, this mycotoxic metabolic product of Penicillium spp. is taken orally [ 11 ]. Griseofulvin is a member of the systemic antifungals class of antifungal medicines, which is a more general group. Its pharmacological application, mode of action, and chemical makeup can all be used to further refine its classification [ 12 ]: Classification of Chemicals: Benzofuranone derivative, because of its unique chemical structure, which consists of a benzene ring bonded to a furanone ring, griseofulvin is categorized as a benzofuranone derivative. Its antifungal efficacy depends on this structure [ 13 – 14 ]. The action's mechanism: antimitotic agent, because it can interfere with fungal cell division and mitosis, griseofulvin is categorized as an antimitotic agent. It prevents the formation of the mitotic spindle required for fungal cell division by interfering with the assembly of microtubules [ 15 ]. Classification of Therapeutics: Griseofulvin is predominantly employed as a systemic antifungal medication. It is used to treat infections caused by dermatophytes that affect the nails, hair, and skin. These illnesses include fungal nail infections (tinea unguium or onychomycosis), and ringworm (tinea corporis) [ 16 ] Nature of Fungistatics: Rather than being categorized as a fungicidal agent, griseofulvin is a fungistatic agent. Although it doesn't always result in the instant death of fungal cells, it prevents the growth and reproduction of fungus by interfering with mitosis [ 17 ]. When antifungal creams are ineffective, griseofulvin, an antifungal drug, is used to treat dermatophytoses of all kinds, including fungal infections of the skin, scalp, and nails. It is an in vitro fungistatic substance derived from Penicillium spp. that is mycotoxic and active against several species of Microsporum, Epidermophyton, and Trichophyton [ 18 ]. Griseofulvin inhibits fungal cell mitosis by adhering to microtubules and obstructing the formation of mitotic spindles, which is how it interferes with the process of fungal cell division [ 19 ]. After oral treatment, it is deposited in the keratin precursor cells and exhibits a higher affinity for tissue that is sick. Since the medication is firmly bonded to the newly formed keratin, it becomes extremely resistant to fungal invasions [ 20 ]. Fungal microtubules (tubulin) are bound by the keratin-Griseofulvin combination once it reaches the skin site of action, changing the course of fungal mitosis. Because griseofulvin acts slowly and takes a while to work. Most treatments take six to ten weeks. It is useless topically and is only used orally for dermatophytosis [ 21 ]. Griseofulvin is a tubulin-inhibiting agent that binds to microtubules and stops the production of mitotic spindles, which inhibits fungal cell mitosis. This interferes with the process of fungal cell division. It is useless when used topically and is only used orally for dermatophytosis. Since griseofulvin acts slowly, most treatments take six to ten weeks to complete [ 22 – 26 ]. 2.0 Computational Methods The structure of griseofulvin was crafted using Gaussview 6.0 software package. Geometry optimization and frequency calculations were carried out on the structure of griseofulvin using the gaussian 09 software package. The Popularly known density functional theory was the method of choice with the Becke three Lee Yang-Parr functional (B3LYP) and the 6–31*(d,p) basis set [ 29 ]. This method provides insights into the energetics, geometry, and electronic structure of molecules, offering a quantum-level understanding. DFT calculations can predict molecular spectra, such as UV-Vis absorption, IR vibrational frequencies, and NMR chemical shifts, providing valuable information about the compound's electronic and vibrational transitions [ 30 , 41 ]. Studying Griseofulvin in different solvents, such as Aqueous Hydrochloric acid, ethanol, and water, is crucial for understanding how the compound behaves in diverse environments. Solvent effects can significantly influence molecular properties, including electronic transitions and conformational changes. Theoretical calculations in various solvents allow for the assessment of solvent-induced shifts in spectral features. The choice of solvents in the study of Griseofulvin's spectral properties is a thoughtful approach to understanding its potential impact on libido-associated problems [ 31 ]. By examining its behavior in ethanol and water, researchers can glean valuable information about the compound's solubility, stability, and interactions in environments that simulate aspects of the gastrointestinal and physiological conditions. This knowledge contributes to a more comprehensive assessment of Griseofulvin's potential harmful effects on libido within the context of its pharmaceutical applications. The solubility of Griseofulvin in various solvents like ethanol, and water, plays a crucial role in determining its bioavailability and subsequent physiological effects, including potential impacts on libido. The choice of solvent influences how readily the compound can be absorbed in the body [ 32 , 33 ]. Additionally, the compound's chemical stability in different solvents is a key factor that may affect its ability to reach target tissues. Changes in chemical structure or reactivity in these diverse environments could have implications for Griseofulvin's pharmacological properties, potentially influencing its overall effect on libido-associated attributes. Overall, an understanding of solubility and chemical stability provides valuable insights into the compound's behavior within the body and its potential physiological consequences. The use of IR spectroscopy offers a holistic view of Griseofulvin's behavior in various solvents. IR spectroscopy offers insights into the compound's overall vibrational characteristics and potential interactions with solvent molecules. Together, these analyses contribute to understanding how Griseofulvin responds to different solvents at the molecular level, shedding light on its solubility, conformational flexibility, and potential implications [ 34 ]. 2.1 Molecular docking Studies The drug under investigation is known as griseofulvin or fulsin. It is a well know antifungal drug which is popularly used in the treatment of ringworm, athlete's foot, jock itch, and fungal infections of the scalp, fingernails, or toenails. Griseofulvin is also known to have certain side effects one of which is the reputable erectile dysfunction. The proteins involved in erectile studies are the Human Phosphodiesterase (PDE) 5 proteins (1UDU and 1UDT) [ 35 , 36 ]. One of the notable roles of PDEs is their involvement in modulating vasodilation, a physiological process that involves the relaxation of smooth muscles, leading to an increase in blood vessel diameter. Erectile dysfunction occurs when there is an imbalance in the regulation of vasodilation and vasoconstriction in the penile region. If PDE activity is elevated, there is a rapid breakdown of cyclic adenosine triphosphate (cAMP) and cyclic guanosine monophosphate (cGMP), limiting its vasodilatory effects and preventing the sustained relaxation of smooth muscles necessary for an erection [ 37 ]. This docking analysis was embarked on in order to trace the reasons why griseofulvin could potentially lead to erectile dysfunction. Griseofulvin was the ligand of interest and was retrieved from Chemspider ( www.chemspider.com ) [ 38 ]. In order to ascertain if other antifungal drugs had the same shortcomings, an examination of the interactions between the other antifungal drugs with Phosphodiesterase (PDE) proteins, known regulators of cyclic nucleotides involved in vasodilation had to be carried out [ 39 ]. By exploring how these drugs may affect PDE proteins, the study brought further insights into the understanding of their potential impact on the cyclic guanosine monophosphate (cGMP) signaling pathway, which plays a crucial role in erectile function. The findings from this investigation contribute valuable insights into the molecular mechanisms underlying the probable side effects of these antifungal drugs, providing critical information for both clinical considerations and further drug development efforts in the antifungal class [ 40 ]. We used AutoDock tools software to prepare the ligands and the protein for a molecular docking simulation to explore the interactions between ligands and proteins. The Docking was prompted using autodock vina and command prompt [ 27 ]. The resulting docked complex was then analyzed in both 2D and 3D formats. For 2D structure visualization, Discovery Studio was employed, while it was used to visualize the complex in 3D [ 28 ]. The 3D structures of the target receptor proteins, specifically Human Phosphodiesterase 5 complexed with tadalafil which is also known as cialis (1UDU) and Human Phosphodiesterase 5 complexed with Sildenafil which is also called viagra (1UDT), were obtained from the Research Collaborator for Structural Bioinformatics (RCSB) protein data bank in its protein database format ( www.RSCPDB.org ) [ 42 ]. 2.2 Pharmacokinetic and Pharmacodynamic Studies This comprehensive assessment is essential for understanding how the drug interacts with the body, both in terms of its therapeutic effects and potential risks. The process begins with examining the drug's absorption characteristics, elucidating how efficiently it is taken up into the bloodstream after administration [ 43 ]. Distribution studies focus on understanding the drug's reach within the body, considering factors such as tissue penetration and binding to proteins [ 44 ]. Metabolism studies investigate how Griseofulvin undergoes chemical transformations in the body, impacting its bioavailability and activity [ 45 ]. Excretion studies explore the elimination routes, ensuring a clear understanding of how the drug is removed from the system. Lastly, toxicity assessments are critical for identifying any adverse effects the drug might induce [ 46 ]. This comprehensive ADMET analysis provides crucial insights that guide further drug development, helping to optimize its safety and efficacy profiles. The pharmacokinetic analysis involved studying how the body processes the drug, encompassing its absorption, distribution, metabolism, and excretion [ 47 ]. Understanding these aspects helped to determine the drug's bioavailability, tissue distribution, and overall systemic exposure. Concurrently, the pharmacodynamic assessment examines how Griseofulvin interacts with its target, elucidating the relationship between drug concentration and its therapeutic effects. In tandem, these analyses provide a comprehensive understanding of the drug's efficacy and potential for side effects or toxicity. was considered and investigated using SwissADME ( http://www.swissadme.ch/index.php ) and pkCSM ( https://biosig.lab.uq.edu.au/pkcsm/prediction ) [ 48 , 49 ]. 3.0 Results Discussion 3.1 Geometric optimization Table 1 Optimized Geometry of Griseofulvin using Solvents of Water and Ethanol Parameter Water Parameter Ethanol R(1–19) 1.794 R(1–19) 1.794 R(2–8) 1.458 R(2–8) 1.458 R(2–15) 1.361 R(2–15) 1.360 R(3–12) 1.343 R(3–12) 1.343 R(3–22) 1.454 R(3–22) 1.453 R(4–11) 1.215 R(4–11) 1.215 R(5–16) 1.220 R(5–16) 1.220 R(6–18) 1.356 R(6–18) 1.355 R(6–23) 1.471 R(6–23) 1.471 R(7–21) 1.340 R(7–21) 1.340 R(7–24) 1.456 R(7–24) 1.455 R(8–9) 1.530 R(8–9) 1.530 R(8–11) 1.546 R(8–11) 1.546 R(8–12) 1.509 R(8–12) 1.509 R(9–10) 1.535 R(9–10) 1.535 R(9–13) 1.535 R(9–13) 1.535 R(9–25) 1.083 R(9–25) 1.083 R(10–16) 1.511 R(10–16) 1.511 R(10–26) 1.081 R(10–26) 1.081 R(10–27) 1.084 R(10–27) 1.084 R(11–14) 1.448 R(11–14) 1.448 R(12–17) 1.325 R(12–17) 1.325 R(13–28) 1.084 R(13–28) 1.084 R(13–29) 1.083 R(13–29) 1.083 R(13–30) 1.083 R(13–30) 1.083 R(14–15) 1.390 R(14–15) 1.391 R(14–18) 1.390 R(14–18) 1.390 R(15–19) 1.357 R(15–19) 1.357 R(16–17) 1.464 R(16–17) 1.464 R(17–31) 1.069 R(17–31) 1.069 R(18–20) 1.384 R(18–20) 1.384 R(19–21) 1.393 R(19–21) 1.393 R(20–21) 1.388 R(20–21) 1.388 R(20–32) 1.066 R(20–32) 1.066 R(22–33) 1.076 R(22–33) 1.076 R(22–34) 1.080 R(22–34) 1.080 R(22–35) 1.080 R(22–35) 1.080 R(23–36) 1.073 R(23–36) 1.073 R(23–37) 1.080 R(23–37) 1.080 R(23–38) 1.076 R(23–38) 1.076 R(24–39) 1.080 R(24–39) 1.080 R(24–40) 1.080 R(24–40) 1.080 R(24–41) 1.076 R(24–41) 1.076 The optimization of the Griseofulvin molecule in both Ethanol and water solvents represents a critical step in understanding and characterizing its behavior in different environments. This comprehensive process holds substantial significance for several key aspects of molecular analysis. Firstly, assessing the molecule's structural stability provides insights into its robustness and potential reactivity under varied conditions [ 50 ]. Characterizing potential reaction pathways is crucial for elucidating how Griseofulvin may undergo transformations or interactions, offering valuable information for predicting its behavior in complex biological and chemical systems that makes up the human stomach. Analyzing molecular interactions is fundamental for understanding how Griseofulvin may interact with surrounding molecules, including solvent molecules or potential binding partners. This knowledge is particularly pertinent in the context of drug design and studies, where predicting and optimizing interactions is essential for the development of effective pharmaceuticals. The calculation of vibrational spectra contributes to the understanding of how the molecule vibrates and moves, providing information on its dynamic behavior. The optimization procedures, carried out using density function theory with the B3LYP/6–31 + G(d,p) level of theory, ensure a robust and accurate representation of the molecule's behavior [ 51 ]. The resulting observations of bond lengths, presented in Table 1 , serve as quantitative indicators of the molecular geometry in each solvent. These observations offer valuable data for further interpreting and predicting the molecule's behavior, aiding in the rational design of drugs and the advancement of drug-related research. Overall, this comprehensive optimization process lays the foundation for a nuanced understanding of Griseofulvin's molecular properties and its potential applications in drug development. The observed correlations between the results obtained using water and ethanol as solvents, as indicated in Table 1 and the optimized geometry in Fig. 1 for Griseofulvin, suggest that the molecule exhibits similar behavior and characteristics in these two different solvent environments. This implies that Griseofulvin is relatively insensitive to the choice of solvent, at least within the context of water and ethanol. The molecule's properties, such as its geometry and other molecular descriptors, appear to be consistent across these solvents. Such consistency in results suggests that Griseofulvin may have a robust and stable molecular structure, showing similar interactions and conformations in both water and ethanol. This information is valuable for understanding the versatility of Griseofulvin and its potential applications in different pharmaceutical formulations or chemical processes that involve varying solvent conditions. Figure 2 depicts the van der Waals spheres surrounding each atom in the Griseofulvin molecule and serves as a visual representation of the molecule's non-covalent interactions [ 52 ]. These spheres encapsulate the hypothetical boundaries where attractive and repulsive forces among atoms find equilibrium, giving us a glimpse into the spatial extent of electron clouds and the delicate balance of van der Waals forces arising from electron distribution fluctuations. Griseofulvin, known for its antifungal properties found in various plants, showcases these spheres to illustrate the intricate interplay between its constituent atoms. This visualization proves instrumental in understanding the molecular structure's nuances, providing crucial insights into the molecule's steric properties. Moreover, the three-dimensional representation offered by the van der Waals spheres offers valuable information about how Griseofulvin may interact with its surrounding environment. By visualizing the spatial arrangement of electron clouds, scientists can infer potential interaction sites and predict how the molecule might engage in non-covalent bonds with other molecules [ 53 ]. This insight is pivotal in comprehending the molecule's behavior within biological systems or when administered as a drug, guiding researchers in optimizing its pharmaceutical properties or exploring its interactions with cellular components. The van der Waals spheres, therefore, become a powerful tool in elucidating Griseofulvin's molecular landscape and its implications for both medicinal and biological applications [ 54 ]. 3.2 Vibrational Frequencies Table 2 Vibrational Frequencies Obtained using DFT’s B3LYP-6-31*G(d,p) functional and basis set Vibrational Mode Frequency (Cm − 1 ) H 2 O Solvent CH 3 CH 2 OH Solvent C = O 1899.241 1899.241 1207.745 1207.745 1109.312 1109.312 465.496 322.900 68.824 69.160 C-H 3420.998 3237.998 3291.750 3291.750 1512.257 1515.210 1715.265 1718.233 1026.940 1036.112 820.760 820.760 465.496 322.900 O-CH₃ 3420.998 3237.998 1334.625 1334.625 1026.940 1036.112 465.496 322.900 C-Cl 392.131 392.131 The IR spectrum of Griseofulvin reveals characteristic absorption bands corresponding to specific vibrational modes due to water being the solvent of interest and hence providing insights into the molecular structure. The absorption bands at 1899 cm⁻¹, 465 cm⁻¹, 1109 cm⁻¹, 1207 cm⁻¹, and 68 cm⁻¹ indicate stretching and bending vibrations of the carbonyl group (C = O). These vibrations are crucial for understanding the functional groups and electronic structure associated with the carbonyl moiety. Vibrations around 1875 cm⁻¹ and 1715 cm⁻¹ are attributed to stretching and bending motions of the double bond in the spirobenzofuran moiety. These peaks provide information about the conjugated system and structural elements in the molecule. The presence of absorption bands at 3420 cm⁻¹, 3291 cm⁻¹, 1512 cm⁻¹, 1715 cm⁻¹, 1026 cm⁻¹, 820 cm⁻¹, and 465 cm⁻¹ indicates stretching and bending vibrations of hydrogen atoms bonded to carbon (C-H). These vibrations are essential for understanding the aliphatic and aromatic hydrocarbon components of Griseofulvin. The absorptions around 3420 cm⁻¹, 1334 cm⁻¹, 1026 cm⁻¹, and 465 cm⁻¹ are associated with stretching and bending vibrations of the methoxy groups (O-CH₃). These peaks provide information about the presence and behavior of methoxy substituents in the molecule. The absorption at 392 cm⁻¹ indicates stretching vibration of the chlorine atom (C-Cl). This peak provides insight into the presence of a chlorine substituent in Griseofulvin. The IR spectrum of Griseofulvin, obtained under the ethanol solvation model, reveals distinctive absorption bands that correspond to specific vibrational modes, offering detailed insights into its molecular structure. The absorption bands centered at 1899 cm⁻¹, 322 cm⁻¹, 1109 cm⁻¹, 1207 cm⁻¹, and 69 cm⁻¹ are indicative of stretching and bending vibrations associated with the carbonyl group (C = O). Understanding these vibrations is crucial for discerning the functional groups and electronic structure related to the carbonyl moiety, which is often integral to the compound's reactivity. Vibrations around 1785 cm⁻¹ and 1715 cm⁻¹ correspond to stretching and bending motions of the double bond, providing valuable information about the conjugated system and overall structural elements in the molecule. The presence of absorption bands at 3237 cm⁻¹, 3291 cm⁻¹, 1512 cm⁻¹, 1715 cm⁻¹, 1036, 820 cm⁻¹, and 322 cm⁻¹ points to stretching and bending vibrations of hydrogen atoms bonded to carbon (C-H). These vibrations are essential for understanding both aliphatic and aromatic hydrocarbon components within Griseofulvin, contributing to its overall structural characterization. Additionally, absorptions around 3237 cm⁻¹, 1334 cm⁻¹, 1026 cm⁻¹, and 322 cm⁻¹ are associated with stretching and bending vibrations of methoxy groups (O-CH₃), shedding light on the presence and behavior of these substituents in the molecule. The absorption peak at 322 cm⁻¹ specifically indicates stretching vibration of the chlorine atom (C-Cl), offering insight into the presence of a chlorine substituent in Griseofulvin The vibrational modes identified in the IR spectrum contribute to a detailed characterization of Griseofulvin's structural features and functional groups. The interpretation of these absorption bands is crucial for understanding the molecular composition and behavior of Griseofulvin, contributing to its broader pharmaceutical and chemical characterization. 3.3 Molecular Docking Studies of Griseofulvin Table 3 Molecular Docking of Griseofulvin and the Target Proteins (1UDT and 1UDU). Ligand Protein Code Binding Affinity (kcal/mol) Amino acid Residue Amino acid Bond’s Distance (Å) Types of Interactions Griseofulvin 1UDT -10.7 GLU682 4.36816 Attractive Charge ASP724 4.68331 Attractive Charge GLU682 4.51069 Attractive Charge ASP724 3.96889 Attractive Charge ASP654 3.95042 Attractive Charge GLU682 4.6178 Attractive Charge ASN662 3.68845 Carbon Hydrogen Bond ASP724: 3.48395 Carbon Hydrogen Bond ASP764: 3.48838 Carbon Hydrogen Bond MG1002 2.25334 Metal-Acceptor Griseofulvin 1UDU -11.5 GLU753 5.04184 Attractive Charge GLU753 4.77093 Attractive Charge ALA719 3.59394 Carbon Hydrogen Bond Upon docking, Griseofulvin showed notable binding affinity towards (binding affinity of -10.7) as the best docking score (Table 3 ). When examining the interactions of griseofulvin with 1UDT and 1UDU as shown in Figs. 5 and 6 respectively, the interactions involved were of three different types; The metal-acceptor interaction, the attractive charge and the carbon hydrogen bond. These interactions were formed between specific amino acid group residues and specific interaction sites on griseofulvin. The presented data delineates the interactions between Griseofulvin and specific amino acids in 1UDT, accompanied by corresponding bond distances. GLU682 engages in multiple attractive charge interactions with Griseofulvin (bond distances: 4.36816, 4.51069, 4.6178), suggesting electrostatic attractions between the negatively charged side chain of GLU682 and positively charged regions of the molecule. Similarly, ASP724 participates in attractive charge interactions and forms a carbon-hydrogen bond with Griseofulvin (bond distances: 4.68331, 3.96889, 3.48395), indicating a specific geometric arrangement between the carbon and hydrogen atoms of the drug and ASP724. ASP654 is involved in an attractive charge interaction (bond distance: 3.95042), emphasizing electrostatic attraction between Griseofulvin and the negatively charged side chain of ASP654. Further interactions include ASN662 and ASP764, both engaging in carbon-hydrogen bond interactions with Griseofulvin (bond distances: 3.68845, 3.48838). These interactions imply specific geometric arrangements between Griseofulvin and the carbon and hydrogen atoms of these amino acids, indicating potential hydrogen bonding interactions. Additionally, MG1002 exhibits a metal-acceptor interaction (bond distance: 2.25334), suggesting coordination with a metal atom in Griseofulvin. Such metal interactions are often crucial for the binding of metal ions in the active sites of proteins. The very short bond-distance between magnesium in the protein and the griseofulvin indicates a very strong metal-acceptor bond. The 1UDU protein (Cialis), had only three interactions when docked with the ligand, of which were weak interactions mainly composed of attractive charges. GLU753 engages in multiple attractive charge interactions with Griseofulvin (bond distances: 5.04184, 4.77093), suggesting electrostatic attractions between the negatively charged side chain of GLU753 and positively charged regions of the molecule. These attractive charge interactions highlight the significance of electrostatic forces in the molecular recognition of Griseofulvin by GLU753. While ALA719 participates in a carbon-hydrogen bond interaction with Griseofulvin (bond distance: 3.59394), indicating a specific geometric arrangement between the carbon and hydrogen atoms of the drug and ALA719. This carbon-hydrogen bond interaction suggests a potential hydrogen bonding interaction, emphasizing the role of specific molecular geometry in the binding of Griseofulvin to ALA719. 3.3.1 Significance of MG1002 Metal-Acceptor Interaction This metal-acceptor interaction between Magnesium and Griseofulvin potentially leads to an abstraction or malfunction of Magnesium found in the human phosphodiesterase 5 proteins (1UDT - Viagra). Magnesium is an essential mineral that plays a crucial role in various physiological functions in the body, including muscle and nerve function, blood glucose control, and blood pressure regulation. Magnesium deficiency has been associated with certain health issues, including cardiovascular problems and muscle cramps [ 55 ]. Erectile dysfunction is a complex condition that can be influenced by various factors, including vascular health, hormonal balance, neurological function, and psychological factors. Studies suggest that magnesium may has a role in promoting cardiovascular health, and since adequate blood flow is essential for normal erectile function, maintaining overall cardiovascular health is important [56]. 3.4 Molecular Docking Studies of Amphotericin B Table 4 Molecular Docking of Amphotericin B and the Target Proteins (1UDT and 1UDU). Ligand Protein Code Binding Affinity (kcal/mol) Amino acid Residue Amino acid Bond’s Distance (Å) Types of Interactions Amphotericin B 1UDT -9.0 ASP838 3.12918 Attractive Charge LYS633 1.92399 Conventional Hydrogen Bond ASP581 3.08609 Conventional Hydrogen Bond ALA631 2.85675 Conventional Hydrogen Bond LYS633 2.00604 Conventional Hydrogen Bond SER560 1.56616 Conventional Hydrogen Bond Amphotericin B 1UDU -9.2 ASN661 2.37994 Conventional Hydrogen Bond ASN661 2.02276 Conventional Hydrogen Bond LYS730 1.42968 Conventional Hydrogen Bond HIS678 2.72045 Pi-Donor Hydrogen Bond TYR664 3.47859 Pi-Sigma Table 4 describes the interactions between Amphotericin B and the amino acids of the 1UDT protein, along with corresponding bond distances (Fig. 6 ). ASP838 engages in an attractive charge interaction with Amphotericin B (bond distance: 3.12918), indicating electrostatic attractions between the negatively charged side chain of ASP838 and positively charged regions of the molecule. This attractive charge interaction underscores the role of electrostatic forces in the molecular recognition of Amphotericin B by ASP838. LYS633 participates in a conventional hydrogen bond interaction with Amphotericin B (bond distance: 1.92399). This type of interaction involves a specific geometric arrangement between the hydrogen and acceptor atoms, highlighting the importance of molecular geometry in the binding of Amphotericin B to LYS633. Similarly, ASP581, ALA631, and another instance of LYS633 engage in conventional hydrogen bond interactions with Amphotericin B, with bond distances of 3.08609, 2.85675, and 2.00604, respectively. These interactions emphasize the significance of specific geometric arrangements involving hydrogen bonding in the molecular recognition of Amphotericin B by these amino acids. SER560 forms a conventional hydrogen bond with Amphotericin B (bond distance: 1.56616), further illustrating the importance of precise molecular geometry in the binding of Amphotericin B to SER560. While the interactions between Amphotericin B and specific amino acids within the 1UDU protein, offers insights beyond mere geometric considerations as can be seen in Fig. 7 . ASN661 establishes conventional hydrogen bonds with Amphotericin B, indicating a molecular interaction influenced by both geometry and electronegativity. These hydrogen bonds contribute to the stabilization of the complex formed between Amphotericin B and ASN661, influencing the overall binding affinity. LYS730 forms a conventional hydrogen bond with Amphotericin B, representing an interaction crucial for molecular recognition and stability. This hydrogen bond involves the sharing of electron pairs between the hydrogen of LYS730 and an electronegative atom in Amphotericin B, contributing to the overall specificity of the binding. HIS678 engages in a pi-donor hydrogen bond, a more nuanced interaction involving the sharing of pi electrons from HIS678 with Amphotericin B. This type of bond not only influences geometry but also showcases the role of electron delocalization in the binding process, adding complexity to the molecular recognition mechanism. TYR664 participates in a pi-sigma interaction, indicating an association between the pi electrons of TYR664 and the sigma electrons of Amphotericin B. This interaction extends beyond simple geometry, emphasizing the importance of electronic interactions and orbital overlap in the binding process. These interactions between Amphotericin B and amino acids within the 1UDU protein involve a delicate interplay of geometric, electrostatic, and electronic factors. They collectively contribute to the stability and specificity of the molecular complex, influencing the overall efficacy of Amphotericin B as it interacts with the 1UDU protein. Understanding these interactions is crucial for unraveling the molecular mechanisms underlying drug-protein interactions and facilitating the design of more effective therapeutic agents. 3.5 Molecular Docking Studies of Ketoconazole Table 5 Molecular Docking Studies of Ketoconazole Ligand Protein Code Binding Affinity (kcal/mol) Amino acid Residue Amino acid Bond’s Distance (Å) Types of Interactions Ketoconazole 1UDT -7.2 ASN614 2.43586 Conventional Hydrogen Bond PHE564 3.45237 Carbon Hydrogen Bond ARG616 3.74877 Pi-Cation ILE778 3.73156 Alkyl TYR612 5.27067 Pi-Alkyl ARG616 3.78045 Pi-Alkyl LEU781 4.68809 Pi-Alkyl Ketoconazole 1UDU -9.0 ARG731 2.32724 Conventional Hydrogen Bond LYS752 2.5301 Conventional Hydrogen Bond LYS752 3.02898 Conventional Hydrogen Bond GLU753 3.32097 Carbon Hydrogen Bond ASN798 3.25538 Carbon Hydrogen Bond LYS714 3.96768 Pi-Cation GLU753 3.07036 Pi-Anion LEU797 3.76954 Pi-Sigma LEU797 4.89973 Alkyl LEU721 4.27146 Alkyl HIS683 4.40764 Pi-Alkyl ARG731 2.32724 Conventional Hydrogen Bond Table 5 unveils interactions between Ketoconazole and certain amino acids within the 1UDT protein, along with corresponding bond distances, shedding light on the complex's overall stability. ASN614 participates in a conventional hydrogen bond with Ketoconazole, with a bond distance of 2.43586 Å. This interaction involves the sharing of a hydrogen atom between ASN614 and Ketoconazole, contributing to the overall stability of the complex through hydrogen bonding. PHE564 forms a carbon-hydrogen bond with Ketoconazole, with a bond distance of 3.45237 Å. This interaction involves the interaction of a hydrogen atom from Ketoconazole with a carbon atom in PHE564, further enhancing the stability of the complex through hydrophobic interactions. ARG616 engages in a pi-cation interaction with Ketoconazole (bond distance: 3.74877 Å), where the pi electrons of Ketoconazole interact with the positively charged cationic center of ARG616. This type of interaction significantly contributes to the stability of the complex through electrostatic attractions. ILE778 forms an alkyl interaction with Ketoconazole, with a bond distance of 3.73156 Å. This interaction involves the hydrophobic interactions between the alkyl groups of Ketoconazole and ILE778, contributing to the overall stability of the complex through van der Waals forces. TYR612 participates in a pi-alkyl interaction with Ketoconazole, with a bond distance of 5.27067. This interaction involves the stacking of the aromatic ring of TYR612 with the alkyl group of Ketoconazole, contributing to the complex's stability through both pi stacking and hydrophobic interactions. ARG616 and LEU781 form pi-alkyl interactions with Ketoconazole, with bond distances of 3.78045 Å and 4.68809 Å, respectively. These interactions involve the stacking of the aromatic ring of Ketoconazole with the alkyl groups of ARG616 and LEU781, further enhancing the overall stability of the complex through van der Waals forces. On the other hand, interactions between Ketoconazole and the 1UDU protein, describes the complex's overall stability and its impact on binding affinity, hydrophilicity, and hydrophobicity. ARG731 forms a conventional hydrogen bond with Ketoconazole, with a bond distance of 2.32724. This hydrogen bond involves the sharing of a hydrogen atom between ARG731 and Ketoconazole, contributing to the overall stability of the complex through electrostatic interactions. The presence of multiple conventional hydrogen bonds, such as those formed by LYS752 (bond distances: 2.5301, 3.02898) and GLU753 (bond distance: 3.32097), further enhances the stability through polar interactions. GLU753 engages in a carbon-hydrogen bond with Ketoconazole (bond distance: 3.07036), contributing to stability through hydrophobic interactions. Similarly, ASN798 forms a carbon-hydrogen bond with a bond distance of 3.25538, further enhancing hydrophobic interactions within the complex. LYS714 participates in a pi-cation interaction with Ketoconazole, involving the stacking of the aromatic ring of Ketoconazole with the positively charged cationic center of LYS714. This interaction enhances the overall stability of the complex through electrostatic attractions. GLU753 forms a pi-anion interaction with Ketoconazole (bond distance: 3.07036), where the pi electrons of Ketoconazole interact with the negatively charged anionic center of GLU753, contributing to stability through electrostatic forces. LEU797 engages in both pi-sigma (bond distance: 3.76954) and alkyl (bond distance: 4.89973) interactions with Ketoconazole, highlighting the significance of both aromatic stacking and hydrophobic interactions in stabilizing the complex. LEU721 and HIS683 contribute to the overall stability through alkyl and pi-alkyl interactions, with bond distances of 4.27146 and 4.40764, respectively. In terms of binding affinity, the diverse interactions contribute to a more intricate and stable binding interface between Ketoconazole and the 1UDT protein. Hydrophilic interactions, such as hydrogen bonding, enhance specificity, while hydrophobic interactions, including alkyl and pi interactions, contribute to the overall stability of the complex. The presence of multiple types of interactions suggests a robust and adaptable binding interface that accommodates various forces. 3.6 Molecular Docking Studies of Terbinafine Table 6 Molecular Docking Studies of Terbinafine Ligand Protein Code Binding Affinity (kcal/mol) Amino acid Residue Amino acid Bond’s Distance (Å) Types of Interactions Terbinafine 1UDT -7.1 PRO841 3.41459 Carbon Hydrogen Bond TRP772 2.86267 Pi-Donor Hydrogen Bond PRO771 3.41101 Pi-Sigma PRO841 4.67532 Alkyl PRO841 4.96026 Alkyl PHE559 5.32106 Pi-Alkyl PRO771 3.98223 Pi-Alkyl LYS848 5.38311 Pi-Alkyl LYS848 4.01022 Pi-Alkyl Terbinafine 1UDU -7.9 GLU753 3.53658 Carbon Hydrogen Bond GLU753 3.78817 Pi-Anion ALA757 4.83731 Alkyl ILE715 5.24332 Pi-Alkyl LYS752 5.07305 Pi-Alkyl From Table 6 it can be seen that PRO841 in the 1UDT protein establishes a carbon-hydrogen bond with Terbinafine (bond distance: 3.41459), contributing to hydrophobic interactions. Additionally, PRO841 forms two alkyl interactions with Terbinafine (bond distances: 4.67532, 4.96026), enhancing the overall stability through hydrophobic forces. TRP772 participates in a pi-donor hydrogen bond with Terbinafine, with a bond distance of 2.86267. This interaction combines aromatic stacking and hydrogen bonding, contributing to the stability of the complex and affecting the binding affinity. PRO771 forms pi-sigma (bond distance: 3.41101) and pi-alkyl (bond distance: 3.98223) interactions with Terbinafine. These interactions involve the aromatic ring of Terbinafine interacting with the sigma electrons and alkyl groups of PRO771, influencing the overall stability of the complex through van der Waals forces. PHE559 contributes to the stability of the complex through a pi-alkyl interaction with Terbinafine (bond distance: 5.32106). This interaction involves the stacking of the aromatic ring of PHE559 with the alkyl group of Terbinafine, enhancing the overall stability through both pi stacking and hydrophobic interactions. LYS848 forms multiple pi-alkyl interactions with Terbinafine (bond distances: 5.38311, 4.01022), emphasizing the importance of these interactions in stabilizing the complex. While the terbinafine interacts with the 1UDU protein in such a way that GLU753 forms a carbon-hydrogen bond with Terbinafine (bond distance: 3.53658), contributing to hydrophobic interactions. Additionally, GLU753 engages in a pi-anion interaction with Terbinafine (bond distance: 3.78817). This interaction involves the pi electrons of Terbinafine interacting with the negatively charged anionic center of GLU753, enhancing the overall stability of the complex through electrostatic forces. ALA757 contributes to the stability of the complex through alkyl interactions with Terbinafine (bond distance: 4.83731), emphasizing the role of hydrophobic forces in molecular recognition. ILE715 forms a pi-alkyl interaction with Terbinafine, with a bond distance of 5.24332. This interaction involves the stacking of the aromatic ring of Terbinafine with the alkyl group of ILE715, enhancing the overall stability through both pi stacking and hydrophobic interactions. LYS752 participates in pi-alkyl interactions with Terbinafine (bond distance: 5.07305), further highlighting the importance of these interactions in stabilizing the complex. Overall, the diverse interactions involving carbon-hydrogen bonds, pi-donor hydrogen bonds, pi-sigma, alkyl, and pi-alkyl interactions contribute to the overall stability of the Terbinafine-1UDT complex. The combination of hydrophobic forces and specific geometric arrangements enhances the binding affinity of Terbinafine to the 1UDT protein. The presence of various interactions underscores the intricate balance of hydrophilic and hydrophobic forces, shaping the molecular recognition and stability of the Terbinafine-1UDT complex. The diverse interactions involving carbon-hydrogen bonds, pi-anion, alkyl, and pi-alkyl interactions collectively contribute to the overall stability of the Terbinafine-1UDU complex. These interactions influence the binding affinity of Terbinafine to the 1UDU protein, with hydrophobic forces playing a significant role in shaping the molecular recognition. The intricate balance of hydrophilic and hydrophobic forces, represented by the various interactions, underscores the complexity of the molecular interactions and their impact on the stability and binding characteristics of the Terbinafine-1UDU complex. 3.7 Absorption, Distribution, Metabolism Excretion and Toxicity Studies of the Griseofulvin Table 7 ADMET profiles of the Griseofulvin Property Parameter Predicted value Absorption (% Absorbed) Human Intestinal Absorption 96.916 Water Solubility -4.388 Distribution BBB Permeability -0.806 CSN Permeability -2.891 Metabolism (Cytochrome P450, CYP) CYP2D6 Substrate No CYP3A4 Substrate Yes CYP1A2 Inhibitor No CYP2C19 Inhibitor No CYP2C9 Inhibitor No CYP2D6 Inhibitor No CYP3A4 Inhibitor Yes Excretion Total clearance 0.685 Toxicity AMES Toxicity No Human Max. tolerated dose (log mg/kg/day) 0.775 The Table 7 clearly describes the ADMET properties of Griseofulvin and showcases notable pharmacokinetic attributes that position it as a promising drug candidate. Its remarkable absorption rate of 96.916% in the human intestine highlights its efficacy in entering the bloodstream after oral administration, suggesting efficient absorption and favorable bioavailability. However, the challenge of its relatively poor water solubility, indicated by a negative value of -4.388, raises concerns about formulation for oral delivery. Overcoming this obstacle is crucial for optimizing the drug's bioavailability and ensuring its therapeutic effectiveness. The distribution profile of Griseofulvin further contributes to its appeal. With a Blood-Brain Barrier (BBB) permeability value of -0.806 and a Central Nervous System (CSN) permeability value of -2.891, the drug demonstrates limited ability to penetrate these critical barriers. This characteristic bodes well for minimizing the risk of neurological side effects or interactions, enhancing the safety profile of Griseofulvin. Additionally, the drug's metabolism, with CYP3A4 as a substrate but not CYP2D6, provides valuable insights into potential drug interactions, guiding clinicians in managing its use in combination with other medications. In considering Griseofulvin's excretion and toxicity parameters, the drug maintains a favorable profile. A total clearance value of 0.685 signifies a balanced elimination rate, contributing to a well-rounded pharmacokinetic profile. Moreover, the absence of mutagenic potential in the AMES test and a relatively low log value (0.775) for the human maximum tolerated dose indicate a reasonable safety margin. In conclusion, while challenges related to water solubility should be addressed in formulation, Griseofulvin's overall pharmacokinetic characteristics make it a promising candidate for further exploration in clinical settings, with careful attention to potential drug interactions and safety considerations. Conclusion In conclusion, this research aimed to explore the potential link between Griseofulvin, an antifungal medication, and its impact on erectile function through a comprehensive computational approach. Utilizing density functional theory (DFT) for optimization and molecular docking studies on Human Phosphodiesterase 5 proteins (PDE5), specifically targeting crystal structures 1UDT and 1UDU, the study investigated the binding mechanisms, allosteric modulation, and conformational changes induced by Griseofulvin. The research extended its analysis to compare Griseofulvin's interactions with other antifungal drugs, including amphotericin, terbinafine, and ketoconazole. The molecular docking results revealed that Griseofulvin exhibited notable binding affinity, emphasizing its potential as a modulator of PDE5. The interactions involved various types, such as metal-acceptor, attractive charge, and carbon-hydrogen bonds, providing insights into the specific amino acid residues involved and their corresponding bond distances. Notably, a significant metal-acceptor interaction with magnesium (MG1002) in the 1UDT protein raised questions about potential implications for magnesium-dependent physiological functions. Further comparative molecular docking studies with other antifungal drugs highlighted Griseofulvin's distinct interactions and reaffirmed its potential as a candidate for impacting PDE5 function. The specific geometric arrangements, electrostatic forces, and electronic factors influencing these interactions underscore the complexity of drug-protein binding mechanisms. Abbreviations Keys: lysine (LYS), alanine (ALA), valine (VAL), tyrosine (TYR), tryptophan (TRP), isoleucine (ILE), phenylalanine (PHE), Proline (PRO), Glutamine (GLU), Arginine (ARG) Aspartate (ASP), Histidine (HIS) and Asparagine (ASN). Declarations Author Contribution J.S and E.E came up with the idea and developed the write up as well as carried out the computations. B.B and S.H reviewed the write up and made valuable input. Data Availability The data supporting the findings of this study, "Investigating the Propagating Effects of Griseofulvin on Erectile Dysfunction: A Comprehensive Computational and Molecular Docking Study on Human Phosphodiesterase 5 Proteins (1UDT and 1UDU)," are available within the article and its supplementary materials. 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In Pharmacology and Therapeutics. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/systemic-antifungal-agent Odds, F., Brown, A., & Gow, N. (2003). Antifungal agents: mechanisms of action. Trends In Microbiology, 11(6), 272-279. https://doi.org/10.1016/s0966-842x(03)00117-3 Magaji, A. Etim, E.E., Ogofotha. G.O Synthesis of Organic Molecules in the Interstellar Medium: A Review. International Journal of Advanced Research in Chemical Science (IJARCS) 2022. 9(2): 17-25 Sung, B. J., Yeon Hwang, K., Ho Jeon, Y., Lee, J. I., Heo, Y. S., Hwan Kim, J., ... & Myung Cho, J. (2003). Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. Nature , 425 (6953), 98-102. Izuagbe G. Osigbemhe, Hitler Louis, Emmanuel M. Khan, Emmanuel E. Etim, Emmanuella E. Oyo-ita, Amoawe P. Oviawe, Henry O. Edet, Faith Obuye. Antibacterial Potential of 2-(-(2-Hydroxyphenyl)-methylidene)-amino)nicotinic Acid: Experimental, DFT Studies, and Molecular Docking Approach. Appl Biochem Biotechnol (2022). https://doi.org/10.1007/s12010-022-04054-9 Baillie, G. S., Tejeda, G. S., & Kelly, M. P. (2019). Therapeutic targeting of 3′, 5′-cyclic nucleotide phosphodiesterases: inhibition and beyond. Nature reviews Drug discovery , 18 (10), 770-796. Izuagbe G.Osigbemhe, Emmanuella E.Oyoitab, HitlerLouis, Emmanuel M.Khan, Emmanuel E.Etim, Henry O.Edet, Onyinye J.Ikenyirimba, Amoawe P.Oviawe, Faith Obuye, (2022). Antibacterial potential of N-(2-furylmethylidene)-1, 3, 4-thiadiazole-2-amine: Experimental and theoretical investigations. Journal of the Indian Chemical Society, 99 (9): 100597. https://www.sciencedirect.com/science/article/abs/pii/S001945222200259X Aris, P., Wei, Y., Mohamadzadeh, M., & Xia, X. (2022). Griseofulvin: An updated overview of old and current knowledge. Molecules , 27 (20), 7034. Samuel, H. S., Etim, E. E., U. Nweke-Maraizu. Approaches for Special Characteristics of Chalcogen Bonding: A mini-Review. Journal Applied Organometallic Chemistry, 2023; 3(3), 199-212. https://doi.org/10.22034/JAOC.2023.405432.1089 Ruswanto, R., Mardianingrum, R., Nofianti, T., Pratita, A. T. K., Naser, F. M., & Siswandono, S. (2023). Design and computational study of the thiourea–cobalt (III) complex as an anticancer candidate. Journal of Pharmacy & Pharmacognosy Research , 11 (3), 499-516. Grimme, S., Brandenburg, J. G., Bannwarth, C., & Hansen, A. (2015). Consistent structures and interactions by density functional theory with small atomic orbital basis sets. The Journal of chemical physics , 143 (5). Fernández, M. A., Silva, O. F., Vico, R. V., & de Rossi, R. H. (2019). Complex systems that incorporate cyclodextrins to get materials for some specific applications. Carbohydrate research , 480 , 12-34. Additional Declarations No competing interests reported. Supplementary Files GA.jpg GA Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4492213","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":312596592,"identity":"bc7893f1-2288-43b6-808b-58a0f921ae5a","order_by":0,"name":"John Shinggu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA40lEQVRIiWNgGAWjYBACxgYeECEBZj8AEjx8pGhhNgBpYSNsD1gLmMUG1khQC3N777GHP3dY5Mn7rzGr/JpjJ8PGwPzw0Q18Dus5l27Me0ai2PDGG7PbstuSgQ5jMzbOwadlRo6ZNGObROLGGWfMbktuYwZq4WGTJqRF8idUS7HktnritEjwArXM5+8xY/y47TARWnrOmEmDtGyQYCuWZtx2nIeNmYBfDNt7QA6rS5zff3jjx5/bqu352ZsfPsarpQHKMLiRwMDMA2Ix41EOAvJwRv8BBsYfBFSPglEwCkbByAQApz9Fv/V2gPAAAAAASUVORK5CYII=","orcid":"","institution":"Federal University Wukari","correspondingAuthor":true,"prefix":"","firstName":"John","middleName":"","lastName":"Shinggu","suffix":""},{"id":312596594,"identity":"4881219b-0881-40f7-ae52-c431dc62a106","order_by":1,"name":"Emmanuel Etim","email":"","orcid":"","institution":"Federal University Wukari","correspondingAuthor":false,"prefix":"","firstName":"Emmanuel","middleName":"","lastName":"Etim","suffix":""},{"id":312596597,"identity":"1c1697c3-c1b0-425f-8024-3da07e41a7f6","order_by":2,"name":"Samuel Humphrey","email":"","orcid":"","institution":"Federal University Wukari","correspondingAuthor":false,"prefix":"","firstName":"Samuel","middleName":"","lastName":"Humphrey","suffix":""},{"id":312596604,"identity":"24bc10d5-c4a4-4a05-b505-d9b09ad0a6cf","order_by":3,"name":"Bulus Bako","email":"","orcid":"","institution":"Federal University Wukari","correspondingAuthor":false,"prefix":"","firstName":"Bulus","middleName":"","lastName":"Bako","suffix":""}],"badges":[],"createdAt":"2024-05-28 16:22:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4492213/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4492213/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58306288,"identity":"df9f59f0-fce1-4465-9d41-5eda9d3d73b3","added_by":"auto","created_at":"2024-06-13 18:27:45","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":41412,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOptimized geometry and Structure of Griseofulvin\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4492213/v1/92ad62f04c7db062498cb909.jpg"},{"id":58305917,"identity":"34944e96-004a-44b4-a223-2343b4059d62","added_by":"auto","created_at":"2024-06-13 18:19:45","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":61969,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eVan-Der Waals Spheres of Griseofulvin\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4492213/v1/3c4801b74dc372126fd45863.jpg"},{"id":58306981,"identity":"d6771177-1cb7-41ab-8657-9a37c42b0092","added_by":"auto","created_at":"2024-06-13 18:35:45","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":48798,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSolvation method of Ethanol\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4492213/v1/f12fe2e0f5bf8c0fb09c28a2.jpg"},{"id":58305920,"identity":"6040f8ff-a469-4f84-93df-df5271a309c5","added_by":"auto","created_at":"2024-06-13 18:19:45","extension":"jpg","order_by":4,"title":"Figure 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18:19:45","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":47686,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAmphotericin interaction with 1UDU (Cialis)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4492213/v1/f19ff823707bde4efaacc7cc.jpg"},{"id":58305932,"identity":"a487c29f-a13a-4358-8ccd-63ee3321a74c","added_by":"auto","created_at":"2024-06-13 18:19:45","extension":"jpg","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":47108,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKetoconazole interaction with 1UDT (Viagra)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4492213/v1/21831ea0744420d01c62e917.jpg"},{"id":58306294,"identity":"6fdfa14a-736b-4668-bb6c-bece37b3b591","added_by":"auto","created_at":"2024-06-13 18:27:45","extension":"jpg","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":50525,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKetoconazole interaction with 1UDU (Cialis)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"9.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4492213/v1/716e8925f0476c9a8a372e5d.jpg"},{"id":58305927,"identity":"20c8cbf7-944e-4582-b8f4-706f0327ca22","added_by":"auto","created_at":"2024-06-13 18:19:45","extension":"jpg","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":40475,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTerbinafine interaction with 1UDT (Viagra)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"10.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4492213/v1/997810a89f6f39bb4e97e43f.jpg"},{"id":58305930,"identity":"fcaaea24-df91-4a2e-b942-123c813f7001","added_by":"auto","created_at":"2024-06-13 18:19:45","extension":"jpg","order_by":12,"title":"Figure 12","display":"","copyAsset":false,"role":"figure","size":36414,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTerbinafine interaction with 1UDU (Cialis)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"11.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4492213/v1/4b0d68fcd96c1199f072c131.jpg"},{"id":58306982,"identity":"a8399bea-3cc3-47e1-86e2-95941848a0c4","added_by":"auto","created_at":"2024-06-13 18:35:45","extension":"jpg","order_by":13,"title":"Figure 13","display":"","copyAsset":false,"role":"figure","size":110807,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e3D Images of Human Phosphodiesterase 5 Proteins of Interest\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"12.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4492213/v1/b6150215510148921da81eae.jpg"},{"id":58305925,"identity":"c2310d8e-ab37-48ff-a3c7-997698ce384d","added_by":"auto","created_at":"2024-06-13 18:19:45","extension":"jpg","order_by":14,"title":"Figure 14","display":"","copyAsset":false,"role":"figure","size":46087,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHOMO-LUMO Iso-Surfaces of Griseofulvin\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"13.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4492213/v1/928cf64e3cf84cd4cf88c549.jpg"},{"id":67733111,"identity":"43122de0-9f53-4f7c-bf1d-62f9e88ce55e","added_by":"auto","created_at":"2024-10-29 07:32:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1887662,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4492213/v1/a07f8491-eb0c-4fb2-b07c-5bd7d3e591bd.pdf"},{"id":58306980,"identity":"e04fca32-da6b-4432-9b2f-8f090e37d453","added_by":"auto","created_at":"2024-06-13 18:35:45","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":88954,"visible":true,"origin":"","legend":"\u003cp\u003eGA\u003c/p\u003e","description":"","filename":"GA.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4492213/v1/c34dda763f80d1f88505b822.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Investigating the Propagating effects of Griseofulvin on Erectile Dysfunction: A Comprehensive Computational and Molecular Docking Study on Human Phosphodiesterase 5 proteins (1UDT and 1UDU).","fulltext":[{"header":"1.0 Introduction","content":"\u003cp\u003eA naturally occurring substance with a variety of biological functions, including antibacterial and antifungal qualities, griseofulvin is obtained from the Penicillium notatum fungus. But little has been discovered about how it might affect erectile function. Antifungal medications are used to treat and prevent fungal infections, which can damage the skin, nails, hair, and internal organs, among other parts of the body [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. These medicines, also referred to as antimycotic drugs, function by either eliminating the fungus or stopping it from proliferating. The class of pharmaceuticals known as antifungal drugs is intended to treat fungal infections by either preventing the growth of the fungus causing the infection or by eliminating it entirely [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. A fungal infection can impact the skin, nails, respiratory system, and internal organs, among other sections of the body. Effective management of these infections has been made possible by the introduction of antifungal medications. There are many different kinds of antifungal medications, including creams, gels, ointments, sprays, pills, capsules, liquids, and injections. They are used to treat a variety of fungal illnesses, such as severe dandruff, athlete's foot, ringworm, and fungal nail infections in the vagina. Aspergillosis (lung infection), fungal meningitis (brain infection), and candidemia (bloodstream infection) are more severe fungal diseases that need to be treated in a hospital. However, there is an increasing risk to global health due to the development of antifungal resistance [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Antifungal medication resistance in fungi can significantly reduce the range of available treatments. Fungi exposed to antifungal medications may naturally develop resistance or resistance may evolve over time [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Typical antifungal drugs include the Canesten (clotrimazole), benzazole, moxizole, lamisil, terbinafine, diflucan or fluconazole, daktarin or ketoconazole, nystan or nystatin, amphetidine. Fulcin, also known as griseofulvin as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, is an oral antifungal drug used to treat a variety of dermatophytoses that has a long history of safety and effectiveness. It has been a significant therapy option for fungal infections for more than 40 years and is processed in the liver [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe impact of griseofulvin on erectile function, however, is not well understood. Only one (0.51%) of the 196 participants in a phase IV clinical study using FDA data reported experiencing impotence as a side effect while using griseofulvin [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. A thorough computational and molecular docking investigation is carried out to see whether griseofulvin has any possible effects on erectile function. The design and synthesis of derivatives of griseofulvin, their molecular docking studies to predict their binding affinity and specificity for target proteins involved in erectile function, and a biological evaluation of the chosen derivatives for their effects on erectile function in vitro and in vivo models could all be part of this study. Additionally, the study looks into the underlying molecular mechanisms of how griseofulvin and its derivatives affect erectile function.\u003c/p\u003e \u003cdiv id=\"Sec2\" class=\"Section2\"\u003e \u003ch2\u003e1.1 Nature and Classification of Griseofulvin\u003c/h2\u003e \u003cp\u003eOnce antifungal creams have failed, griseofulvin, an antifungal drug, is used to treat a variety of dermatophytoses, including fungal infections of the skin, scalp, and nails. As a tubulin-inhibiting agent, it works by reducing mitosis to provide its physiological impact. Mycotoxic Griseofulvin is an antifungal polyketide metabolite mostly produced by ascomycetes and a byproduct of Penicillium species metabolism [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Since the drug is useless when applied topically, it must be taken orally and is only useful for dermatophytosis. Griseofulvin is a suspension that can be taken orally and has a well-established track record of safety and effectiveness. Sometimes dosage changes are required because of the liver's role in its metabolism. With a lengthy history of safety and effectiveness, griseofulvin is a tubulin-inhibiting agent that is mostly used to treat dermatophytoses. Because it is inefficient when used topically, this mycotoxic metabolic product of Penicillium spp. is taken orally [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGriseofulvin is a member of the systemic antifungals class of antifungal medicines, which is a more general group. Its pharmacological application, mode of action, and chemical makeup can all be used to further refine its classification [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eClassification of Chemicals: Benzofuranone derivative, because of its unique chemical structure, which consists of a benzene ring bonded to a furanone ring, griseofulvin is categorized as a benzofuranone derivative. Its antifungal efficacy depends on this structure [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe action's mechanism: antimitotic agent, because it can interfere with fungal cell division and mitosis, griseofulvin is categorized as an antimitotic agent. It prevents the formation of the mitotic spindle required for fungal cell division by interfering with the assembly of microtubules [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eClassification of Therapeutics: Griseofulvin is predominantly employed as a systemic antifungal medication. It is used to treat infections caused by dermatophytes that affect the nails, hair, and skin. These illnesses include fungal nail infections (tinea unguium or onychomycosis), and ringworm (tinea corporis) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eNature of Fungistatics: Rather than being categorized as a fungicidal agent, griseofulvin is a fungistatic agent. Although it doesn't always result in the instant death of fungal cells, it prevents the growth and reproduction of fungus by interfering with mitosis [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eWhen antifungal creams are ineffective, griseofulvin, an antifungal drug, is used to treat dermatophytoses of all kinds, including fungal infections of the skin, scalp, and nails. It is an in vitro fungistatic substance derived from Penicillium spp. that is mycotoxic and active against several species of Microsporum, Epidermophyton, and Trichophyton [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Griseofulvin inhibits fungal cell mitosis by adhering to microtubules and obstructing the formation of mitotic spindles, which is how it interferes with the process of fungal cell division [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. After oral treatment, it is deposited in the keratin precursor cells and exhibits a higher affinity for tissue that is sick. Since the medication is firmly bonded to the newly formed keratin, it becomes extremely resistant to fungal invasions [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Fungal microtubules (tubulin) are bound by the keratin-Griseofulvin combination once it reaches the skin site of action, changing the course of fungal mitosis. Because griseofulvin acts slowly and takes a while to work. Most treatments take six to ten weeks. It is useless topically and is only used orally for dermatophytosis [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Griseofulvin is a tubulin-inhibiting agent that binds to microtubules and stops the production of mitotic spindles, which inhibits fungal cell mitosis. This interferes with the process of fungal cell division. It is useless when used topically and is only used orally for dermatophytosis. Since griseofulvin acts slowly, most treatments take six to ten weeks to complete [\u003cspan additionalcitationids=\"CR23 CR24 CR25\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"2.0 Computational Methods","content":"\u003cp\u003eThe structure of griseofulvin was crafted using Gaussview 6.0 software package. Geometry optimization and frequency calculations were carried out on the structure of griseofulvin using the gaussian 09 software package. The Popularly known density functional theory was the method of choice with the Becke three Lee Yang-Parr functional (B3LYP) and the 6\u0026ndash;31*(d,p) basis set [\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e]. This method provides insights into the energetics, geometry, and electronic structure of molecules, offering a quantum-level understanding. DFT calculations can predict molecular spectra, such as UV-Vis absorption, IR vibrational frequencies, and NMR chemical shifts, providing valuable information about the compound\u0026apos;s electronic and vibrational transitions [\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e41\u003c/span\u003e]. Studying Griseofulvin in different solvents, such as Aqueous Hydrochloric acid, ethanol, and water, is crucial for understanding how the compound behaves in diverse environments. Solvent effects can significantly influence molecular properties, including electronic transitions and conformational changes. Theoretical calculations in various solvents allow for the assessment of solvent-induced shifts in spectral features. The choice of solvents in the study of Griseofulvin\u0026apos;s spectral properties is a thoughtful approach to understanding its potential impact on libido-associated problems [\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e]. By examining its behavior in ethanol and water, researchers can glean valuable information about the compound\u0026apos;s solubility, stability, and interactions in environments that simulate aspects of the gastrointestinal and physiological conditions. This knowledge contributes to a more comprehensive assessment of Griseofulvin\u0026apos;s potential harmful effects on libido within the context of its pharmaceutical applications.\u003c/p\u003e\n\u003cp\u003eThe solubility of Griseofulvin in various solvents like ethanol, and water, plays a crucial role in determining its bioavailability and subsequent physiological effects, including potential impacts on libido. The choice of solvent influences how readily the compound can be absorbed in the body [\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e]. Additionally, the compound\u0026apos;s chemical stability in different solvents is a key factor that may affect its ability to reach target tissues. Changes in chemical structure or reactivity in these diverse environments could have implications for Griseofulvin\u0026apos;s pharmacological properties, potentially influencing its overall effect on libido-associated attributes. Overall, an understanding of solubility and chemical stability provides valuable insights into the compound\u0026apos;s behavior within the body and its potential physiological consequences. The use of IR spectroscopy offers a holistic view of Griseofulvin\u0026apos;s behavior in various solvents. IR spectroscopy offers insights into the compound\u0026apos;s overall vibrational characteristics and potential interactions with solvent molecules. Together, these analyses contribute to understanding how Griseofulvin responds to different solvents at the molecular level, shedding light on its solubility, conformational flexibility, and potential implications [\u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003e2.1 Molecular docking Studies\u003c/h3\u003e\n\u003cp\u003eThe drug under investigation is known as griseofulvin or fulsin. It is a well know antifungal drug which is popularly used in the treatment of ringworm, athlete\u0026apos;s foot, jock itch, and fungal infections of the scalp, fingernails, or toenails. Griseofulvin is also known to have certain side effects one of which is the reputable erectile dysfunction. The proteins involved in erectile studies are the Human Phosphodiesterase (PDE) 5 proteins (1UDU and 1UDT) [\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e36\u003c/span\u003e]. One of the notable roles of PDEs is their involvement in modulating vasodilation, a physiological process that involves the relaxation of smooth muscles, leading to an increase in blood vessel diameter. Erectile dysfunction occurs when there is an imbalance in the regulation of vasodilation and vasoconstriction in the penile region. If PDE activity is elevated, there is a rapid breakdown of cyclic adenosine triphosphate (cAMP) and cyclic guanosine monophosphate (cGMP), limiting its vasodilatory effects and preventing the sustained relaxation of smooth muscles necessary for an erection [\u003cspan class=\"CitationRef\"\u003e37\u003c/span\u003e]. This docking analysis was embarked on in order to trace the reasons why griseofulvin could potentially lead to erectile dysfunction. Griseofulvin was the ligand of interest and was retrieved from Chemspider (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ewww.chemspider.com\u003c/span\u003e\u003c/span\u003e) [\u003cspan class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eIn order to ascertain if other antifungal drugs had the same shortcomings, an examination of the interactions between the other antifungal drugs with Phosphodiesterase (PDE) proteins, known regulators of cyclic nucleotides involved in vasodilation had to be carried out [\u003cspan class=\"CitationRef\"\u003e39\u003c/span\u003e]. By exploring how these drugs may affect PDE proteins, the study brought further insights into the understanding of their potential impact on the cyclic guanosine monophosphate (cGMP) signaling pathway, which plays a crucial role in erectile function. The findings from this investigation contribute valuable insights into the molecular mechanisms underlying the probable side effects of these antifungal drugs, providing critical information for both clinical considerations and further drug development efforts in the antifungal class [\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eWe used AutoDock tools software to prepare the ligands and the protein for a molecular docking simulation to explore the interactions between ligands and proteins. The Docking was prompted using autodock vina and command prompt [\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e]. The resulting docked complex was then analyzed in both 2D and 3D formats. For 2D structure visualization, Discovery Studio was employed, while it was used to visualize the complex in 3D [\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e]. The 3D structures of the target receptor proteins, specifically Human Phosphodiesterase 5 complexed with tadalafil which is also known as cialis (1UDU) and Human Phosphodiesterase 5 complexed with Sildenafil which is also called viagra (1UDT), were obtained from the Research Collaborator for Structural Bioinformatics (RCSB) protein data bank in its protein database format (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ewww.RSCPDB.org\u003c/span\u003e\u003c/span\u003e) [\u003cspan class=\"CitationRef\"\u003e42\u003c/span\u003e].\u003c/p\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003e2.2 Pharmacokinetic and Pharmacodynamic Studies\u003c/h2\u003e\n \u003cp\u003eThis comprehensive assessment is essential for understanding how the drug interacts with the body, both in terms of its therapeutic effects and potential risks. The process begins with examining the drug\u0026apos;s absorption characteristics, elucidating how efficiently it is taken up into the bloodstream after administration [\u003cspan class=\"CitationRef\"\u003e43\u003c/span\u003e]. Distribution studies focus on understanding the drug\u0026apos;s reach within the body, considering factors such as tissue penetration and binding to proteins [\u003cspan class=\"CitationRef\"\u003e44\u003c/span\u003e]. Metabolism studies investigate how Griseofulvin undergoes chemical transformations in the body, impacting its bioavailability and activity [\u003cspan class=\"CitationRef\"\u003e45\u003c/span\u003e]. Excretion studies explore the elimination routes, ensuring a clear understanding of how the drug is removed from the system. Lastly, toxicity assessments are critical for identifying any adverse effects the drug might induce [\u003cspan class=\"CitationRef\"\u003e46\u003c/span\u003e]. This comprehensive ADMET analysis provides crucial insights that guide further drug development, helping to optimize its safety and efficacy profiles. The pharmacokinetic analysis involved studying how the body processes the drug, encompassing its absorption, distribution, metabolism, and excretion [\u003cspan class=\"CitationRef\"\u003e47\u003c/span\u003e]. Understanding these aspects helped to determine the drug\u0026apos;s bioavailability, tissue distribution, and overall systemic exposure. Concurrently, the pharmacodynamic assessment examines how Griseofulvin interacts with its target, elucidating the relationship between drug concentration and its therapeutic effects. In tandem, these analyses provide a comprehensive understanding of the drug\u0026apos;s efficacy and potential for side effects or toxicity. was considered and investigated using SwissADME (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.swissadme.ch/index.php\u003c/span\u003e\u003c/span\u003e) and pkCSM (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://biosig.lab.uq.edu.au/pkcsm/prediction\u003c/span\u003e\u003c/span\u003e) [\u003cspan class=\"CitationRef\"\u003e48\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e49\u003c/span\u003e].\u003c/p\u003e\n\u003c/div\u003e"},{"header":"3.0 Results Discussion","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Geometric optimization\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOptimized Geometry of Griseofulvin using Solvents of Water and Ethanol\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWater\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEthanol\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(1–19)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.794\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(1–19)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.794\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(2–8)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.458\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(2–8)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.458\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(2–15)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.361\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(2–15)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.360\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(3–12)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.343\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(3–12)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.343\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(3–22)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.454\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(3–22)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.453\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(4–11)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.215\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(4–11)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.215\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(5–16)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.220\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(5–16)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.220\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(6–18)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.356\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(6–18)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.355\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(6–23)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.471\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(6–23)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.471\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(7–21)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.340\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(7–21)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.340\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(7–24)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.456\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(7–24)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.455\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(8–9)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.530\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(8–9)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.530\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(8–11)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.546\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(8–11)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.546\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(8–12)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.509\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(8–12)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.509\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(9–10)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.535\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(9–10)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.535\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(9–13)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.535\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(9–13)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.535\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(9–25)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.083\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(9–25)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.083\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(10–16)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.511\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(10–16)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.511\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(10–26)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.081\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(10–26)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.081\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(10–27)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.084\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(10–27)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.084\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(11–14)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.448\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(11–14)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.448\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(12–17)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.325\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(12–17)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.325\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(13–28)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.084\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(13–28)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.084\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(13–29)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.083\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(13–29)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.083\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(13–30)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.083\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(13–30)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.083\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(14–15)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.390\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(14–15)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.391\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(14–18)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.390\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(14–18)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.390\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(15–19)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.357\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(15–19)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.357\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(16–17)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.464\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(16–17)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.464\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(17–31)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.069\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(17–31)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.069\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(18–20)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.384\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(18–20)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.384\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(19–21)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.393\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(19–21)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.393\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(20–21)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.388\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(20–21)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.388\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(20–32)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.066\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(20–32)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.066\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(22–33)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.076\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(22–33)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.076\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(22–34)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.080\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(22–34)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.080\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(22–35)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.080\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(22–35)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.080\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(23–36)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.073\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(23–36)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.073\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(23–37)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.080\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(23–37)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.080\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(23–38)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.076\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(23–38)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.076\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(24–39)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.080\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(24–39)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.080\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(24–40)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.080\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(24–40)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.080\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR(24–41)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.076\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eR(24–41)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.076\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e \u003cp\u003e\u003c/p\u003e \u003cp\u003eThe optimization of the Griseofulvin molecule in both Ethanol and water solvents represents a critical step in understanding and characterizing its behavior in different environments. This comprehensive process holds substantial significance for several key aspects of molecular analysis. Firstly, assessing the molecule's structural stability provides insights into its robustness and potential reactivity under varied conditions [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Characterizing potential reaction pathways is crucial for elucidating how Griseofulvin may undergo transformations or interactions, offering valuable information for predicting its behavior in complex biological and chemical systems that makes up the human stomach.\u003c/p\u003e \u003cp\u003eAnalyzing molecular interactions is fundamental for understanding how Griseofulvin may interact with surrounding molecules, including solvent molecules or potential binding partners. This knowledge is particularly pertinent in the context of drug design and studies, where predicting and optimizing interactions is essential for the development of effective pharmaceuticals. The calculation of vibrational spectra contributes to the understanding of how the molecule vibrates and moves, providing information on its dynamic behavior.\u003c/p\u003e \u003cp\u003eThe optimization procedures, carried out using density function theory with the B3LYP/6–31 + G(d,p) level of theory, ensure a robust and accurate representation of the molecule's behavior [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. The resulting observations of bond lengths, presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, serve as quantitative indicators of the molecular geometry in each solvent. These observations offer valuable data for further interpreting and predicting the molecule's behavior, aiding in the rational design of drugs and the advancement of drug-related research. Overall, this comprehensive optimization process lays the foundation for a nuanced understanding of Griseofulvin's molecular properties and its potential applications in drug development.\u003c/p\u003e \u003cp\u003eThe observed correlations between the results obtained using water and ethanol as solvents, as indicated in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and the optimized geometry in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e for Griseofulvin, suggest that the molecule exhibits similar behavior and characteristics in these two different solvent environments. This implies that Griseofulvin is relatively insensitive to the choice of solvent, at least within the context of water and ethanol. The molecule's properties, such as its geometry and other molecular descriptors, appear to be consistent across these solvents. Such consistency in results suggests that Griseofulvin may have a robust and stable molecular structure, showing similar interactions and conformations in both water and ethanol. This information is valuable for understanding the versatility of Griseofulvin and its potential applications in different pharmaceutical formulations or chemical processes that involve varying solvent conditions.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e depicts the van der Waals spheres surrounding each atom in the Griseofulvin molecule and serves as a visual representation of the molecule's non-covalent interactions [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. These spheres encapsulate the hypothetical boundaries where attractive and repulsive forces among atoms find equilibrium, giving us a glimpse into the spatial extent of electron clouds and the delicate balance of van der Waals forces arising from electron distribution fluctuations. Griseofulvin, known for its antifungal properties found in various plants, showcases these spheres to illustrate the intricate interplay between its constituent atoms. This visualization proves instrumental in understanding the molecular structure's nuances, providing crucial insights into the molecule's steric properties.\u003c/p\u003e \u003cp\u003eMoreover, the three-dimensional representation offered by the van der Waals spheres offers valuable information about how Griseofulvin may interact with its surrounding environment. By visualizing the spatial arrangement of electron clouds, scientists can infer potential interaction sites and predict how the molecule might engage in non-covalent bonds with other molecules [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. This insight is pivotal in comprehending the molecule's behavior within biological systems or when administered as a drug, guiding researchers in optimizing its pharmaceutical properties or exploring its interactions with cellular components. The van der Waals spheres, therefore, become a powerful tool in elucidating Griseofulvin's molecular landscape and its implications for both medicinal and biological applications [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e54\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Vibrational Frequencies\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eVibrational Frequencies Obtained using DFT’s B3LYP-6-31*G(d,p) functional and basis set\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVibrational Mode\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eFrequency (Cm\u003csup\u003e− 1\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eH\u003csub\u003e2\u003c/sub\u003eO Solvent\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCH\u003csub\u003e3\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003eOH Solvent\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e\u003cb\u003eC = O\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1899.241\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1899.241\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1207.745\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1207.745\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1109.312\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1109.312\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e465.496\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e322.900\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e68.824\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e69.160\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003e\u003cb\u003eC-H\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3420.998\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3237.998\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3291.750\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3291.750\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1512.257\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1515.210\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1715.265\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1718.233\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1026.940\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1036.112\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e820.760\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e820.760\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e465.496\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e322.900\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u003cb\u003eO-CH₃\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3420.998\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3237.998\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1334.625\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1334.625\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1026.940\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1036.112\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e465.496\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e322.900\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eC-Cl\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e392.131\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e392.131\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e \u003cp\u003e\u003c/p\u003e \u003cp\u003eThe IR spectrum of Griseofulvin reveals characteristic absorption bands corresponding to specific vibrational modes due to water being the solvent of interest and hence providing insights into the molecular structure. The absorption bands at 1899 cm⁻¹, 465 cm⁻¹, 1109 cm⁻¹, 1207 cm⁻¹, and 68 cm⁻¹ indicate stretching and bending vibrations of the carbonyl group (C = O). These vibrations are crucial for understanding the functional groups and electronic structure associated with the carbonyl moiety. Vibrations around 1875 cm⁻¹ and 1715 cm⁻¹ are attributed to stretching and bending motions of the double bond in the spirobenzofuran moiety. These peaks provide information about the conjugated system and structural elements in the molecule. The presence of absorption bands at 3420 cm⁻¹, 3291 cm⁻¹, 1512 cm⁻¹, 1715 cm⁻¹, 1026 cm⁻¹, 820 cm⁻¹, and 465 cm⁻¹ indicates stretching and bending vibrations of hydrogen atoms bonded to carbon (C-H). These vibrations are essential for understanding the aliphatic and aromatic hydrocarbon components of Griseofulvin. The absorptions around 3420 cm⁻¹, 1334 cm⁻¹, 1026 cm⁻¹, and 465 cm⁻¹ are associated with stretching and bending vibrations of the methoxy groups (O-CH₃). These peaks provide information about the presence and behavior of methoxy substituents in the molecule. The absorption at 392 cm⁻¹ indicates stretching vibration of the chlorine atom (C-Cl). This peak provides insight into the presence of a chlorine substituent in Griseofulvin.\u003c/p\u003e \u003cp\u003eThe IR spectrum of Griseofulvin, obtained under the ethanol solvation model, reveals distinctive absorption bands that correspond to specific vibrational modes, offering detailed insights into its molecular structure. The absorption bands centered at 1899 cm⁻¹, 322 cm⁻¹, 1109 cm⁻¹, 1207 cm⁻¹, and 69 cm⁻¹ are indicative of stretching and bending vibrations associated with the carbonyl group (C = O). Understanding these vibrations is crucial for discerning the functional groups and electronic structure related to the carbonyl moiety, which is often integral to the compound's reactivity. Vibrations around 1785 cm⁻¹ and 1715 cm⁻¹ correspond to stretching and bending motions of the double bond, providing valuable information about the conjugated system and overall structural elements in the molecule. The presence of absorption bands at 3237 cm⁻¹, 3291 cm⁻¹, 1512 cm⁻¹, 1715 cm⁻¹, 1036, 820 cm⁻¹, and 322 cm⁻¹ points to stretching and bending vibrations of hydrogen atoms bonded to carbon (C-H). These vibrations are essential for understanding both aliphatic and aromatic hydrocarbon components within Griseofulvin, contributing to its overall structural characterization. Additionally, absorptions around 3237 cm⁻¹, 1334 cm⁻¹, 1026 cm⁻¹, and 322 cm⁻¹ are associated with stretching and bending vibrations of methoxy groups (O-CH₃), shedding light on the presence and behavior of these substituents in the molecule. The absorption peak at 322 cm⁻¹ specifically indicates stretching vibration of the chlorine atom (C-Cl), offering insight into the presence of a chlorine substituent in Griseofulvin\u003c/p\u003e \u003cp\u003eThe vibrational modes identified in the IR spectrum contribute to a detailed characterization of Griseofulvin's structural features and functional groups. The interpretation of these absorption bands is crucial for understanding the molecular composition and behavior of Griseofulvin, contributing to its broader pharmaceutical and chemical characterization.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Molecular Docking Studies of Griseofulvin\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eMolecular Docking of Griseofulvin and the Target Proteins (1UDT and 1UDU).\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLigand\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eProtein Code\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBinding Affinity (kcal/mol)\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAmino acid Residue\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAmino acid Bond’s Distance (Å)\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTypes of Interactions\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"9\" rowspan=\"10\"\u003e \u003cp\u003eGriseofulvin\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"9\" rowspan=\"10\"\u003e \u003cp\u003e1UDT\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"9\" rowspan=\"10\"\u003e \u003cp\u003e-10.7\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLU682\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.36816\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAttractive Charge\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eASP724\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.68331\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAttractive Charge\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLU682\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.51069\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAttractive Charge\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eASP724\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.96889\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAttractive Charge\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eASP654\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.95042\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAttractive Charge\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLU682\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.6178\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAttractive Charge\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eASN662\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.68845\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCarbon Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eASP724:\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.48395\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCarbon Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eASP764:\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.48838\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCarbon Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMG1002\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.25334\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMetal-Acceptor\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eGriseofulvin\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e1UDU\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e-11.5\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLU753\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.04184\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAttractive Charge\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLU753\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.77093\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAttractive Charge\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eALA719\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.59394\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCarbon Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e \u003cp\u003e\u003c/p\u003e \u003cp\u003eUpon docking, Griseofulvin showed notable binding affinity towards (binding affinity of -10.7) as the best docking score (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). When examining the interactions of griseofulvin with 1UDT and 1UDU as shown in Figs.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e5\u003c/span\u003e and \u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e6\u003c/span\u003e respectively, the interactions involved were of three different types; The metal-acceptor interaction, the attractive charge and the carbon hydrogen bond. These interactions were formed between specific amino acid group residues and specific interaction sites on griseofulvin.\u003c/p\u003e \u003cp\u003eThe presented data delineates the interactions between Griseofulvin and specific amino acids in 1UDT, accompanied by corresponding bond distances. GLU682 engages in multiple attractive charge interactions with Griseofulvin (bond distances: 4.36816, 4.51069, 4.6178), suggesting electrostatic attractions between the negatively charged side chain of GLU682 and positively charged regions of the molecule. Similarly, ASP724 participates in attractive charge interactions and forms a carbon-hydrogen bond with Griseofulvin (bond distances: 4.68331, 3.96889, 3.48395), indicating a specific geometric arrangement between the carbon and hydrogen atoms of the drug and ASP724. ASP654 is involved in an attractive charge interaction (bond distance: 3.95042), emphasizing electrostatic attraction between Griseofulvin and the negatively charged side chain of ASP654. Further interactions include ASN662 and ASP764, both engaging in carbon-hydrogen bond interactions with Griseofulvin (bond distances: 3.68845, 3.48838). These interactions imply specific geometric arrangements between Griseofulvin and the carbon and hydrogen atoms of these amino acids, indicating potential hydrogen bonding interactions. Additionally, MG1002 exhibits a metal-acceptor interaction (bond distance: 2.25334), suggesting coordination with a metal atom in Griseofulvin. Such metal interactions are often crucial for the binding of metal ions in the active sites of proteins. The very short bond-distance between magnesium in the protein and the griseofulvin indicates a very strong metal-acceptor bond.\u003c/p\u003e \u003cp\u003eThe 1UDU protein (Cialis), had only three interactions when docked with the ligand, of which were weak interactions mainly composed of attractive charges. GLU753 engages in multiple attractive charge interactions with Griseofulvin (bond distances: 5.04184, 4.77093), suggesting electrostatic attractions between the negatively charged side chain of GLU753 and positively charged regions of the molecule. These attractive charge interactions highlight the significance of electrostatic forces in the molecular recognition of Griseofulvin by GLU753. While ALA719 participates in a carbon-hydrogen bond interaction with Griseofulvin (bond distance: 3.59394), indicating a specific geometric arrangement between the carbon and hydrogen atoms of the drug and ALA719. This carbon-hydrogen bond interaction suggests a potential hydrogen bonding interaction, emphasizing the role of specific molecular geometry in the binding of Griseofulvin to ALA719.\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003e3.3.1 Significance of MG1002 Metal-Acceptor Interaction\u003c/h2\u003e \u003cp\u003eThis metal-acceptor interaction between Magnesium and Griseofulvin potentially leads to an abstraction or malfunction of Magnesium found in the human phosphodiesterase 5 proteins (1UDT - Viagra). Magnesium is an essential mineral that plays a crucial role in various physiological functions in the body, including muscle and nerve function, blood glucose control, and blood pressure regulation. Magnesium deficiency has been associated with certain health issues, including cardiovascular problems and muscle cramps [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. Erectile dysfunction is a complex condition that can be influenced by various factors, including vascular health, hormonal balance, neurological function, and psychological factors. Studies suggest that magnesium may has a role in promoting cardiovascular health, and since adequate blood flow is essential for normal erectile function, maintaining overall cardiovascular health is important [56].\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Molecular Docking Studies of Amphotericin B\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMolecular Docking of Amphotericin B and the Target Proteins (1UDT and 1UDU).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLigand\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eProtein Code\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBinding Affinity (kcal/mol)\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAmino acid Residue\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAmino acid Bond’s Distance (Å)\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTypes of Interactions\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003eAmphotericin B\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e1UDT\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e-9.0\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eASP838\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.12918\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAttractive Charge\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLYS633\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.92399\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eConventional Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eASP581\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.08609\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eConventional Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eALA631\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.85675\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eConventional Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLYS633\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.00604\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eConventional Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSER560\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.56616\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eConventional Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eAmphotericin B\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e1UDU\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e-9.2\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eASN661\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.37994\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eConventional Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eASN661\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.02276\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eConventional Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLYS730\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.42968\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eConventional Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHIS678\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.72045\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Donor Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTYR664\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.47859\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Sigma\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e \u003cp\u003e\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e describes the interactions between Amphotericin B and the amino acids of the 1UDT protein, along with corresponding bond distances (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e6\u003c/span\u003e). ASP838 engages in an attractive charge interaction with Amphotericin B (bond distance: 3.12918), indicating electrostatic attractions between the negatively charged side chain of ASP838 and positively charged regions of the molecule. This attractive charge interaction underscores the role of electrostatic forces in the molecular recognition of Amphotericin B by ASP838. LYS633 participates in a conventional hydrogen bond interaction with Amphotericin B (bond distance: 1.92399). This type of interaction involves a specific geometric arrangement between the hydrogen and acceptor atoms, highlighting the importance of molecular geometry in the binding of Amphotericin B to LYS633. Similarly, ASP581, ALA631, and another instance of LYS633 engage in conventional hydrogen bond interactions with Amphotericin B, with bond distances of 3.08609, 2.85675, and 2.00604, respectively. These interactions emphasize the significance of specific geometric arrangements involving hydrogen bonding in the molecular recognition of Amphotericin B by these amino acids. SER560 forms a conventional hydrogen bond with Amphotericin B (bond distance: 1.56616), further illustrating the importance of precise molecular geometry in the binding of Amphotericin B to SER560.\u003c/p\u003e \u003cp\u003eWhile the interactions between Amphotericin B and specific amino acids within the 1UDU protein, offers insights beyond mere geometric considerations as can be seen in Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e7\u003c/span\u003e. ASN661 establishes conventional hydrogen bonds with Amphotericin B, indicating a molecular interaction influenced by both geometry and electronegativity. These hydrogen bonds contribute to the stabilization of the complex formed between Amphotericin B and ASN661, influencing the overall binding affinity. LYS730 forms a conventional hydrogen bond with Amphotericin B, representing an interaction crucial for molecular recognition and stability. This hydrogen bond involves the sharing of electron pairs between the hydrogen of LYS730 and an electronegative atom in Amphotericin B, contributing to the overall specificity of the binding. HIS678 engages in a pi-donor hydrogen bond, a more nuanced interaction involving the sharing of pi electrons from HIS678 with Amphotericin B. This type of bond not only influences geometry but also showcases the role of electron delocalization in the binding process, adding complexity to the molecular recognition mechanism. TYR664 participates in a pi-sigma interaction, indicating an association between the pi electrons of TYR664 and the sigma electrons of Amphotericin B. This interaction extends beyond simple geometry, emphasizing the importance of electronic interactions and orbital overlap in the binding process. These interactions between Amphotericin B and amino acids within the 1UDU protein involve a delicate interplay of geometric, electrostatic, and electronic factors. They collectively contribute to the stability and specificity of the molecular complex, influencing the overall efficacy of Amphotericin B as it interacts with the 1UDU protein. Understanding these interactions is crucial for unraveling the molecular mechanisms underlying drug-protein interactions and facilitating the design of more effective therapeutic agents.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Molecular Docking Studies of Ketoconazole\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMolecular Docking Studies of Ketoconazole\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLigand\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eProtein Code\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBinding Affinity (kcal/mol)\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAmino acid Residue\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAmino acid Bond’s Distance (Å)\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTypes of Interactions\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003eKetoconazole\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003e1UDT\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003e-7.2\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eASN614\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.43586\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eConventional Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePHE564\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.45237\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCarbon Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARG616\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.74877\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Cation\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eILE778\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.73156\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAlkyl\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTYR612\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.27067\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Alkyl\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARG616\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.78045\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Alkyl\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLEU781\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.68809\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Alkyl\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"11\" rowspan=\"12\"\u003e \u003cp\u003eKetoconazole\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"11\" rowspan=\"12\"\u003e \u003cp\u003e1UDU\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"11\" rowspan=\"12\"\u003e \u003cp\u003e-9.0\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARG731\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.32724\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eConventional Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLYS752\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.5301\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eConventional Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLYS752\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.02898\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eConventional Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLU753\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.32097\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCarbon Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eASN798\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.25538\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCarbon Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLYS714\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.96768\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Cation\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLU753\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.07036\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Anion\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLEU797\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.76954\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Sigma\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLEU797\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.89973\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAlkyl\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLEU721\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.27146\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAlkyl\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHIS683\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.40764\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Alkyl\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eARG731\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.32724\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eConventional Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e \u003cp\u003e\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e unveils interactions between Ketoconazole and certain amino acids within the 1UDT protein, along with corresponding bond distances, shedding light on the complex's overall stability. ASN614 participates in a conventional hydrogen bond with Ketoconazole, with a bond distance of 2.43586 Å. This interaction involves the sharing of a hydrogen atom between ASN614 and Ketoconazole, contributing to the overall stability of the complex through hydrogen bonding. PHE564 forms a carbon-hydrogen bond with Ketoconazole, with a bond distance of 3.45237 Å. This interaction involves the interaction of a hydrogen atom from Ketoconazole with a carbon atom in PHE564, further enhancing the stability of the complex through hydrophobic interactions. ARG616 engages in a pi-cation interaction with Ketoconazole (bond distance: 3.74877 Å), where the pi electrons of Ketoconazole interact with the positively charged cationic center of ARG616. This type of interaction significantly contributes to the stability of the complex through electrostatic attractions. ILE778 forms an alkyl interaction with Ketoconazole, with a bond distance of 3.73156 Å. This interaction involves the hydrophobic interactions between the alkyl groups of Ketoconazole and ILE778, contributing to the overall stability of the complex through van der Waals forces. TYR612 participates in a pi-alkyl interaction with Ketoconazole, with a bond distance of 5.27067. This interaction involves the stacking of the aromatic ring of TYR612 with the alkyl group of Ketoconazole, contributing to the complex's stability through both pi stacking and hydrophobic interactions. ARG616 and LEU781 form pi-alkyl interactions with Ketoconazole, with bond distances of 3.78045 Å and 4.68809 Å, respectively. These interactions involve the stacking of the aromatic ring of Ketoconazole with the alkyl groups of ARG616 and LEU781, further enhancing the overall stability of the complex through van der Waals forces.\u003c/p\u003e \u003cp\u003eOn the other hand, interactions between Ketoconazole and the 1UDU protein, describes the complex's overall stability and its impact on binding affinity, hydrophilicity, and hydrophobicity. ARG731 forms a conventional hydrogen bond with Ketoconazole, with a bond distance of 2.32724. This hydrogen bond involves the sharing of a hydrogen atom between ARG731 and Ketoconazole, contributing to the overall stability of the complex through electrostatic interactions. The presence of multiple conventional hydrogen bonds, such as those formed by LYS752 (bond distances: 2.5301, 3.02898) and GLU753 (bond distance: 3.32097), further enhances the stability through polar interactions. GLU753 engages in a carbon-hydrogen bond with Ketoconazole (bond distance: 3.07036), contributing to stability through hydrophobic interactions. Similarly, ASN798 forms a carbon-hydrogen bond with a bond distance of 3.25538, further enhancing hydrophobic interactions within the complex. LYS714 participates in a pi-cation interaction with Ketoconazole, involving the stacking of the aromatic ring of Ketoconazole with the positively charged cationic center of LYS714. This interaction enhances the overall stability of the complex through electrostatic attractions. GLU753 forms a pi-anion interaction with Ketoconazole (bond distance: 3.07036), where the pi electrons of Ketoconazole interact with the negatively charged anionic center of GLU753, contributing to stability through electrostatic forces. LEU797 engages in both pi-sigma (bond distance: 3.76954) and alkyl (bond distance: 4.89973) interactions with Ketoconazole, highlighting the significance of both aromatic stacking and hydrophobic interactions in stabilizing the complex. LEU721 and HIS683 contribute to the overall stability through alkyl and pi-alkyl interactions, with bond distances of 4.27146 and 4.40764, respectively.\u003c/p\u003e \u003cp\u003eIn terms of binding affinity, the diverse interactions contribute to a more intricate and stable binding interface between Ketoconazole and the 1UDT protein. Hydrophilic interactions, such as hydrogen bonding, enhance specificity, while hydrophobic interactions, including alkyl and pi interactions, contribute to the overall stability of the complex. The presence of multiple types of interactions suggests a robust and adaptable binding interface that accommodates various forces.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.6 Molecular Docking Studies of Terbinafine\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMolecular Docking Studies of Terbinafine\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLigand\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eProtein Code\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBinding Affinity (kcal/mol)\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAmino acid Residue\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAmino acid Bond’s Distance (Å)\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTypes of Interactions\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"8\" rowspan=\"9\"\u003e \u003cp\u003eTerbinafine\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"8\" rowspan=\"9\"\u003e \u003cp\u003e1UDT\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"8\" rowspan=\"9\"\u003e \u003cp\u003e-7.1\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePRO841\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.41459\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCarbon Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTRP772\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.86267\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Donor Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePRO771\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.41101\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Sigma\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePRO841\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.67532\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAlkyl\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePRO841\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.96026\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAlkyl\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePHE559\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.32106\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Alkyl\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePRO771\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.98223\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Alkyl\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLYS848\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.38311\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Alkyl\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLYS848\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.01022\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Alkyl\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eTerbinafine\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e1UDU\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e-7.9\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLU753\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.53658\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCarbon Hydrogen Bond\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGLU753\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.78817\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Anion\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eALA757\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.83731\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAlkyl\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eILE715\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.24332\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Alkyl\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLYS752\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.07305\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePi-Alkyl\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e \u003cp\u003e\u003c/p\u003e \u003cp\u003eFrom Table \u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e it can be seen that PRO841 in the 1UDT protein establishes a carbon-hydrogen bond with Terbinafine (bond distance: 3.41459), contributing to hydrophobic interactions. Additionally, PRO841 forms two alkyl interactions with Terbinafine (bond distances: 4.67532, 4.96026), enhancing the overall stability through hydrophobic forces. TRP772 participates in a pi-donor hydrogen bond with Terbinafine, with a bond distance of 2.86267. This interaction combines aromatic stacking and hydrogen bonding, contributing to the stability of the complex and affecting the binding affinity. PRO771 forms pi-sigma (bond distance: 3.41101) and pi-alkyl (bond distance: 3.98223) interactions with Terbinafine. These interactions involve the aromatic ring of Terbinafine interacting with the sigma electrons and alkyl groups of PRO771, influencing the overall stability of the complex through van der Waals forces. PHE559 contributes to the stability of the complex through a pi-alkyl interaction with Terbinafine (bond distance: 5.32106). This interaction involves the stacking of the aromatic ring of PHE559 with the alkyl group of Terbinafine, enhancing the overall stability through both pi stacking and hydrophobic interactions. LYS848 forms multiple pi-alkyl interactions with Terbinafine (bond distances: 5.38311, 4.01022), emphasizing the importance of these interactions in stabilizing the complex.\u003c/p\u003e \u003cp\u003eWhile the terbinafine interacts with the 1UDU protein in such a way that GLU753 forms a carbon-hydrogen bond with Terbinafine (bond distance: 3.53658), contributing to hydrophobic interactions. Additionally, GLU753 engages in a pi-anion interaction with Terbinafine (bond distance: 3.78817). This interaction involves the pi electrons of Terbinafine interacting with the negatively charged anionic center of GLU753, enhancing the overall stability of the complex through electrostatic forces. ALA757 contributes to the stability of the complex through alkyl interactions with Terbinafine (bond distance: 4.83731), emphasizing the role of hydrophobic forces in molecular recognition. ILE715 forms a pi-alkyl interaction with Terbinafine, with a bond distance of 5.24332. This interaction involves the stacking of the aromatic ring of Terbinafine with the alkyl group of ILE715, enhancing the overall stability through both pi stacking and hydrophobic interactions. LYS752 participates in pi-alkyl interactions with Terbinafine (bond distance: 5.07305), further highlighting the importance of these interactions in stabilizing the complex.\u003c/p\u003e \u003cp\u003eOverall, the diverse interactions involving carbon-hydrogen bonds, pi-donor hydrogen bonds, pi-sigma, alkyl, and pi-alkyl interactions contribute to the overall stability of the Terbinafine-1UDT complex. The combination of hydrophobic forces and specific geometric arrangements enhances the binding affinity of Terbinafine to the 1UDT protein. The presence of various interactions underscores the intricate balance of hydrophilic and hydrophobic forces, shaping the molecular recognition and stability of the Terbinafine-1UDT complex. The diverse interactions involving carbon-hydrogen bonds, pi-anion, alkyl, and pi-alkyl interactions collectively contribute to the overall stability of the Terbinafine-1UDU complex. These interactions influence the binding affinity of Terbinafine to the 1UDU protein, with hydrophobic forces playing a significant role in shaping the molecular recognition. The intricate balance of hydrophilic and hydrophobic forces, represented by the various interactions, underscores the complexity of the molecular interactions and their impact on the stability and binding characteristics of the Terbinafine-1UDU complex.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.7 Absorption, Distribution, Metabolism Excretion and Toxicity Studies of the Griseofulvin\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eADMET profiles of the Griseofulvin\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProperty\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePredicted value\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAbsorption (% Absorbed)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHuman Intestinal Absorption\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96.916\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWater Solubility\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-4.388\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDistribution\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBBB Permeability\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.806\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCSN Permeability\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.891\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003eMetabolism (Cytochrome P450, CYP)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCYP2D6 Substrate\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCYP3A4 Substrate\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCYP1A2 Inhibitor\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCYP2C19 Inhibitor\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCYP2C9 Inhibitor\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCYP2D6 Inhibitor\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCYP3A4 Inhibitor\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExcretion\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal clearance\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.685\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eToxicity\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAMES Toxicity\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHuman Max. tolerated dose (log mg/kg/day)\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.775\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e \u003cp\u003e\u003c/p\u003e \u003cp\u003eThe Table \u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e clearly describes the ADMET properties of Griseofulvin and showcases notable pharmacokinetic attributes that position it as a promising drug candidate. Its remarkable absorption rate of 96.916% in the human intestine highlights its efficacy in entering the bloodstream after oral administration, suggesting efficient absorption and favorable bioavailability. However, the challenge of its relatively poor water solubility, indicated by a negative value of -4.388, raises concerns about formulation for oral delivery. Overcoming this obstacle is crucial for optimizing the drug's bioavailability and ensuring its therapeutic effectiveness.\u003c/p\u003e \u003cp\u003eThe distribution profile of Griseofulvin further contributes to its appeal. With a Blood-Brain Barrier (BBB) permeability value of -0.806 and a Central Nervous System (CSN) permeability value of -2.891, the drug demonstrates limited ability to penetrate these critical barriers. This characteristic bodes well for minimizing the risk of neurological side effects or interactions, enhancing the safety profile of Griseofulvin. Additionally, the drug's metabolism, with CYP3A4 as a substrate but not CYP2D6, provides valuable insights into potential drug interactions, guiding clinicians in managing its use in combination with other medications.\u003c/p\u003e \u003cp\u003eIn considering Griseofulvin's excretion and toxicity parameters, the drug maintains a favorable profile. A total clearance value of 0.685 signifies a balanced elimination rate, contributing to a well-rounded pharmacokinetic profile. Moreover, the absence of mutagenic potential in the AMES test and a relatively low log value (0.775) for the human maximum tolerated dose indicate a reasonable safety margin. In conclusion, while challenges related to water solubility should be addressed in formulation, Griseofulvin's overall pharmacokinetic characteristics make it a promising candidate for further exploration in clinical settings, with careful attention to potential drug interactions and safety considerations.\u003c/p\u003e "},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, this research aimed to explore the potential link between Griseofulvin, an antifungal medication, and its impact on erectile function through a comprehensive computational approach. Utilizing density functional theory (DFT) for optimization and molecular docking studies on Human Phosphodiesterase 5 proteins (PDE5), specifically targeting crystal structures 1UDT and 1UDU, the study investigated the binding mechanisms, allosteric modulation, and conformational changes induced by Griseofulvin. The research extended its analysis to compare Griseofulvin's interactions with other antifungal drugs, including amphotericin, terbinafine, and ketoconazole. The molecular docking results revealed that Griseofulvin exhibited notable binding affinity, emphasizing its potential as a modulator of PDE5. The interactions involved various types, such as metal-acceptor, attractive charge, and carbon-hydrogen bonds, providing insights into the specific amino acid residues involved and their corresponding bond distances. Notably, a significant metal-acceptor interaction with magnesium (MG1002) in the 1UDT protein raised questions about potential implications for magnesium-dependent physiological functions. Further comparative molecular docking studies with other antifungal drugs highlighted Griseofulvin's distinct interactions and reaffirmed its potential as a candidate for impacting PDE5 function. The specific geometric arrangements, electrostatic forces, and electronic factors influencing these interactions underscore the complexity of drug-protein binding mechanisms.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eKeys:\u0026nbsp;\u003c/strong\u003elysine (LYS), alanine (ALA), valine (VAL), tyrosine (TYR), tryptophan (TRP), isoleucine (ILE), phenylalanine (PHE), Proline (PRO), Glutamine (GLU), Arginine (ARG) Aspartate (ASP), Histidine (HIS) and Asparagine (ASN).\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJ.S and E.E came up with the idea and developed the write up as well as carried out the computations. B.B and S.H reviewed the write up and made valuable input.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data supporting the findings of this study, \"Investigating the Propagating Effects of Griseofulvin on Erectile Dysfunction: A Comprehensive Computational and Molecular Docking Study on Human Phosphodiesterase 5 Proteins (1UDT and 1UDU),\" are available within the article and its supplementary materials. Additional data, including the molecular docking and dynamics simulation results, optimization files, and binding free energy calculations, are available from the corresponding author, John Shinggu ([email protected]), upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePetersen, A. B., R\u0026oslash;nnest, M. H., Larsen, T. O., \u0026amp; Clausen, M. H. (2014). The Chemistry of Griseofulvin. 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Complex systems that incorporate cyclodextrins to get materials for some specific applications. \u003cem\u003eCarbohydrate research\u003c/em\u003e, \u003cem\u003e480\u003c/em\u003e, 12-34.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4492213/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4492213/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eErectile dysfunction (ED) is a prevalent condition affecting a significant portion of the male population. This research delves into the potential link between Griseofulvin, a known antifungal medication, and its impact on erectile function. A comprehensive computational approach was employed. Optimization of griseofulvin was carried out using the highly reputable density functional theory (DFT) with the B3LYP functional and 6\u0026ndash;31*G(d,p) using water and ethanol as the solvents of interest. We explored the interactions of Griseofulvin with Human Phosphodiesterase 5 proteins (PDE5), specifically targeting the crystal structures 1UDT and 1UDU. Molecular docking studies provided valuable insights into the binding mechanisms of Griseofulvin with PDE5, shedding light on potential allosteric modulation and conformational changes. Further molecular docking studies were carried out on other popular antifungal drugs like amphotericin, terbinafine and ketoconazole in order to compare their interactions with 1UDT and 1UDU with that of griseofulvin. Through an array of computational analyses, including molecular dynamics simulations and binding free energy calculations, we aimed to elucidate the propagating effects of Griseofulvin on the catalytic activity and structural stability of PDE5. The findings from this research could contribute to a deeper understanding of the molecular mechanisms underlying Griseofulvin's impact on erectile function, potentially opening avenues for the development of novel therapeutic interventions for ED.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e","manuscriptTitle":"Investigating the Propagating effects of Griseofulvin on Erectile Dysfunction: A Comprehensive Computational and Molecular Docking Study on Human Phosphodiesterase 5 proteins (1UDT and 1UDU).","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-13 18:19:40","doi":"10.21203/rs.3.rs-4492213/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bbb48738-fce9-44ce-b151-d10ce1a3ae6d","owner":[],"postedDate":"June 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-10-29T07:24:02+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-13 18:19:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4492213","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4492213","identity":"rs-4492213","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}