In silico comparison of apigenin and related compounds with diverse pharmacological activities using AutoDock 4.2.6

In silico comparison of apigenin and related compounds with diverse pharmacological activities using AutoDock 4.2.6 | 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 In silico comparison of apigenin and related compounds with diverse pharmacological activities using AutoDock 4.2.6 Tanat Peanlikhit, Uma Aryal, James Welsh, Kenneth Shroyer, Kanokporn Rithidech This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4224843/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 In recent years, molecular docking has been used to predict the binding affinity and interaction between flavonoids (ligands) and specific protein targets (receptors). However, existing studies have focused on a limited number of flavonoids with a small number of targeted proteins. In this study, on the other hand, we used the AutoDock 4.2.6 molecular docking software to compare the binding energy values and interactions of apigenin and 15 flavonoids with 24 different proteins known to be associated with oxidative stress, inflammation, carcinogenesis, and bacterial infections. This comparison will be important for the development of flavonoid-based drugs, allowing for the optimization of flavonoid drugs to better interact with their target proteins alone or in combination with conventional drugs. We used three-dimensional crystal structures of the receptors to identify the amino acids in the active site for docking purposes. Our goal was to identify potential inhibitors of these proteins and understand the structural configurations of flavonoids that affect their binding energy (binding affinity or inhibitory effects). We found that apigenin was a highly effective inhibitor for all tested proteins, with the highest binding energy of -8.21 kcal/mol with p38 mitogen-activated protein kinases and the lowest binding energy of -5.34 kcal/mol with cyclin-dependent kinase 4. In fact, apigenin and most of the tested flavonoids were better inhibitors for xanthine oxidase or DNA methyltransferase than known inhibitors. Our results also suggest that apigenin and selected flavonoids could be used to inhibit the oncogenic activity of KRAS mutations at codon 12 (i.e., G12C, G12D, and G12V) frequently found in solid tumors since they possess high binding energies with these mutated proteins. This finding offers an advantage over targeted therapy drugs that focus on specific KRAS mutations. Furthermore, most flavonoids have good safety profiles, so our resulting data are crucial for developing flavonoid-based drugs and present new insights into developing effective treatments that can attenuate the resistance and side effects of chemotherapy. apigenin flavonoids molecular docking AutoDock 4.2 Full Text Additional Declarations No competing interests reported. Supplementary Files TableS1Supplementalmaterial.docx 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. 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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-4224843","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":288796110,"identity":"50672f67-c4d7-4646-a2d3-4f7ed8c91d56","order_by":0,"name":"Tanat Peanlikhit","email":"","orcid":"","institution":"Stony Brook University","correspondingAuthor":false,"prefix":"","firstName":"Tanat","middleName":"","lastName":"Peanlikhit","suffix":""},{"id":288796111,"identity":"1004e20d-ec0a-4e2f-80c2-f1c50ab2de08","order_by":1,"name":"Uma Aryal","email":"","orcid":"","institution":"Purdue University West 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However, existing studies have focused on a limited number of flavonoids with a small number of targeted proteins. In this study, on the other hand, we used the AutoDock 4.2.6 molecular docking software to compare the binding energy values and interactions of apigenin and 15 flavonoids with 24 different proteins known to be associated with oxidative stress, inflammation, carcinogenesis, and bacterial infections. This comparison will be important for the development of flavonoid-based drugs, allowing for the optimization of flavonoid drugs to better interact with their target proteins alone or in combination with conventional drugs. We used three-dimensional crystal structures of the receptors to identify the amino acids in the active site for docking purposes. Our goal was to identify potential inhibitors of these proteins and understand the structural configurations of flavonoids that affect their binding energy (binding affinity or inhibitory effects). We found that apigenin was a highly effective inhibitor for all tested proteins, with the highest binding energy of -8.21 kcal/mol with p38 mitogen-activated protein kinases and the lowest binding energy of -5.34 kcal/mol with cyclin-dependent kinase 4. In fact, apigenin and most of the tested flavonoids were better inhibitors for xanthine oxidase or DNA methyltransferase than known inhibitors. Our results also suggest that apigenin and selected flavonoids could be used to inhibit the oncogenic activity of KRAS mutations at codon 12 (i.e., G12C, G12D, and G12V) frequently found in solid tumors since they possess high binding energies with these mutated proteins. This finding offers an advantage over targeted therapy drugs that focus on specific KRAS mutations. 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