Exploring Moringa oleifera Phytochemicals as Potential Inhibitors for HIF- 1α/VEGF/GLUT1 pathway in Breast Cancer Using Molecular Docking, MD Simulations, and DFT Analysis

Exploring Moringa oleifera Phytochemicals as Potential Inhibitors for HIF- 1α/VEGF/GLUT1 pathway in Breast Cancer Using Molecular Docking, MD Simulations, and DFT Analysis | 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 Article Exploring Moringa oleifera Phytochemicals as Potential Inhibitors for HIF- 1α/VEGF/GLUT1 pathway in Breast Cancer Using Molecular Docking, MD Simulations, and DFT Analysis Neha Masarkar, Maynak Pal, Alakesh Bisai, Ashish K Yadav, Mithun Roy, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6394662/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Oct, 2025 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Breast cancer is among the most heterogeneous and aggressive diseases and a foremost cause of death in women globally. Hypoxic activation of HIF-1α in breast cancers triggers the transcription of a battery of genes encoding proteins that facilitate tumor growth and metastasis and is correlated with a poor prognosis. Based on the reported cytotoxic and anti-cancer properties of Moringa oleifera (Mo) , this study explores the inhibitory effect of bioactive compounds AA and BITC from Moringa oleifera and Breast cancer target proteins HIF-1α, VEGF, and GLUT1 in silico . The X-ray crystallographic structures of HIF-1α, VEGF, and GLUT1 were sourced from the Protein Data Bank (PDB) and docked with 3D PubChem structures of bioactive compounds of AA and BITC using AutoDock Vina, and binding modes were analyzed using Discovery Studio. further drug-likeness, oral bioavailability, ADME, and toxicity profiles were analyzed using SwissADME, ADMETSaR, and ADMETlab 3.0 web server. Complexes were subjected to molecular dynamic simulation (MDS) analysis using Desmond Schrodinger v2019. Then, density functional theory (DFT) studies were performed to measure the active compound’s reactivity, with the help of Gaussian 09 software. Molecular docking results indicated that the ligands interact strongly with the target HIF-1α, VEGF, and GLUT1 receptors through Hydrogen bonds and hydrophobic interactions. These compounds showed favorable drug-like and pharmacokinetic properties, possessed no substantial toxicity, and were fairly bioavailable. The root-mean-square deviation (RMSD) graphs obtained through the molecular dynamic simulations indicated the true bonding interactions, further validated using the root-mean-square fluctuation (RMSF) graphs which provided a better understanding of the amino acids present in the proteins responsible for the molecular motions and fluctuations. Results suggested that the compounds possess strong potential in developing putative lead compounds targeting HIF-1α that are safe natural plant-based drugs against Breast cancer. Biological sciences/Chemical biology Health sciences/Medical research Breast Cancer GLUT1 HIF-1α In- silico Moringa oleifera VEGF Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 22 Oct, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 14 May, 2025 Reviews received at journal 13 May, 2025 Reviews received at journal 13 May, 2025 Reviewers agreed at journal 13 May, 2025 Reviewers agreed at journal 13 May, 2025 Reviewers invited by journal 13 May, 2025 Editor assigned by journal 13 May, 2025 Editor invited by journal 06 May, 2025 Submission checks completed at journal 05 May, 2025 First submitted to journal 07 Apr, 2025 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. 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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-6394662","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":456277061,"identity":"58a6508d-c7eb-4e79-a5ff-a2bc93ece21a","order_by":0,"name":"Neha Masarkar","email":"","orcid":"","institution":"All India Institute of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Neha","middleName":"","lastName":"Masarkar","suffix":""},{"id":456277062,"identity":"dd356674-0668-4d4d-8f75-fab6197febaf","order_by":1,"name":"Maynak Pal","email":"","orcid":"","institution":"National Institute of Technology Manipur. 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Hypoxic activation of HIF-1α in breast cancers triggers the transcription of a battery of genes encoding proteins that facilitate tumor growth and metastasis and is correlated with a poor prognosis. Based on the reported cytotoxic and anti-cancer properties of \u003cem\u003eMoringa oleifera (Mo)\u003c/em\u003e, this study explores the inhibitory effect of bioactive compounds AA and BITC from \u003cem\u003eMoringa oleifera\u003c/em\u003e and Breast cancer target proteins HIF-1α, VEGF, and GLUT1 \u003cem\u003ein silico\u003c/em\u003e. The X-ray crystallographic structures of HIF-1α, VEGF, and GLUT1 were sourced from the Protein Data Bank (PDB) and docked with 3D PubChem structures of bioactive compounds of AA and BITC using AutoDock Vina, and binding modes were analyzed using Discovery Studio. further drug-likeness, oral bioavailability, ADME, and toxicity profiles were analyzed using SwissADME, ADMETSaR, and ADMETlab 3.0 web server. 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