Molecular Docking And In Silico Analysis Of Parkia Biglobosa Bioactive Compounds For Inhibition Of Acetylcholinesterase And L-Amino Acid Oxidase In Snake Venom-Induced Systemic Toxicity

Molecular Docking And In Silico Analysis Of Parkia Biglobosa Bioactive Compounds For Inhibition Of Acetylcholinesterase And L-Amino Acid Oxidase In Snake Venom-Induced Systemic Toxicity | 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 Molecular Docking And In Silico Analysis Of Parkia Biglobosa Bioactive Compounds For Inhibition Of Acetylcholinesterase And L-Amino Acid Oxidase In Snake Venom-Induced Systemic Toxicity Iyiola Aanuoluwa Temitayo, Orjiewulu Vivian Chidera, Charles-Ukeagu Love, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9632624/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 Snakebite envenoming is a significant neglected tropical disease with a high mortality and morbidity burden, especially in resource-constrained areas, in which the systemic toxicity is mediated by enzymes like acetylcholinesterase (AChE) and L-amino acid oxidase (LAAO). Despite the ethnomedicinal use of Parkia biglobosa in managing envenomation, its bioactive constituents lack detailed molecular-level validation and integrated pharmacokinetic characterisation. This study investigated the inhibitory potential of selected P. biglobosa phytochemicals against AChE and LAAO using an integrative molecular docking and in silico pharmacokinetic approach. Eight bioactive compounds were selected from the plant, while edrophonium and aristolochic acid were used as control inhibitors in this study. The 3D structures of the bioactive compounds and the control inhibitors were retrieved from the PubChem database. Additionally, the crystal structures of acetylcholinesterase (4QWW) and L-amino acid oxidase (5Z2G) were obtained from the Protein Data Bank (PDB). Using the RDKit cheminformatics package, the drug-likeness of the bioactive compounds was assessed, and AutoDock Vina was employed for molecular docking with the target proteins. The docked complexes were analysed with BIOVIA Discovery Studio Visualizer. Additionally, the Mordred and RDKit libraries were used to identify the ADMET properties of the ligands. Quercetin and luteolin were the best candidates with desirable binding affinities, with quercetin strongly binding AChE (−9.9 kcal/mol; Ki ≈ 0.06 μM) outperforming the reference inhibitor edrophonium, and luteolin displaying a competitive affinity towards LAAO (−9.5 kcal/mol; Ki ≈ 0.11 μM). Each of the lead compounds met Lipinski requirements, exhibited high predicted gastrointestinal absorption and acceptable toxicity profiles. These results imply that flavonoid scaffolds of P. biglobosa might engage with important catalytic sites in both enzymes, and thereby may mediate neurotoxic and cytotoxic pathways of envenomation, which are molecular-level-supported indicators of the ethnopharmacological significance of P. biglobosa, and may be useful as a complement to antivenom therapy in snakebite envenomation. Further, molecular dynamics, in vitro and in vivo studies are required to validate these results. Computational Biology General Biochemistry Drug Discovery, Design, & Development Parkia biglobosa Snakebite envenomation Molecular docking Acetylcholinesterase L-amino acid oxidase ADMET profiling Full Text Additional Declarations The authors declare no competing interests. Ethics approval, consent to participate, consent to publish : Not applicable Consent for Publication : All the authors approved the manuscript for publication Data and/or code availability : All data generated or analysed during this study are included in this published article. Further enquiries can be directed to the corresponding author Competing interest : The authors declare that we have no competing interests Funding : This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author contributions : Study concept and design: I.A, O.C, C.L. Data collection: O.C, A.O, F.T. Methodology: I.A, O.A, O.O, M.H, I.E. Software: I.A, I.E, M.H, O.C. Supervision: I,A, C.L, O.O; Validation: A.O, O.O and I.A. Writing- original draft: F.T, C.L, I.A. Writing- review & editing: I.A, I.EM.H and O.V. All authors have read, edited, and contributed to the content of this manuscript. This work has not been previously published and has not been considered for publication elsewhere. Acknowledgements : We would like to express our sincere gratitude to all authors for their invaluable contributions and intellectual support during the preparation of this manuscript. 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. 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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-9632624","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":635634252,"identity":"1eac40cd-ebc7-4fbc-ad77-160edae612db","order_by":0,"name":"Iyiola Aanuoluwa 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