In vitro and in silico evaluation of a novel piperazine–tetrazole ligand against breast cancer cell lines: An integrated study of DFT, molecular docking, and molecular dynamics simulations

In vitro and in silico evaluation of a novel piperazine–tetrazole ligand against breast cancer cell lines: An integrated study of DFT, molecular docking, and molecular dynamics simulations | 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 vitro and in silico evaluation of a novel piperazine–tetrazole ligand against breast cancer cell lines: An integrated study of DFT, molecular docking, and molecular dynamics simulations Matheswaran Palanisamy, Sugan Sundaravadivelu, Venugopal Thiruvengadam, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7289669/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 (4-(4-(1H-tetrazole-5-yl)benzyl)piperazin-1yl)(furan-2-yl)methanone (TBFM), a novel piperazine and tetrazole derivative, was synthesized through a two-step process. The structure of the synthesized compound was confirmed using 1 H NMR, LC-MS, and FTIR analyses.The compound’s cytotoxicity was evaluated against the MCF-7 breast cancer cell line using the MTT assay, with an IC50 value of 57.37 µM. Density Functional Theory (DFT) calculations showed a small energy gap of 0.172 eV, suggesting potentially higher biological activity. Further analysis, including non-covalent interaction (NCI) and electron localization function (ELF) studies, indicated that the tetrazole moiety contributes significantly to the molecule’s activity. Molecular docking was performed with 24 proteins from the MCF-7 cell line to explore TBFM’s binding interactions. Among these, proteins 1ZUA, 2SRC, 4RJ3, and 5IEV exhibited stronger interactions with TBFM, with 5IEV showing the highest docking score of -9.9 kcal/mol. The ADMET profile of TBFM was also assessed, revealing no violations of Lipinski's Rule of Five, indicating favourable drug-like properties. Molecular dynamics simulations were conducted for 100 ns to assess the stability of the protein–ligand complexes under near-physiological conditions. The root mean square deviation (RMSD) values for all four proteins werelow, suggesting stable complex formation. Principal component analysis (PCA) showed that the 1ZUA complex formed a compact, oval-shaped cluster. Additionally, Molecular Mechanics Poisson–Boltzmann Surface Area (MMPBSA) calculations estimated the binding free energy of TBFM with each protein, revealing that 2SRC had the highest binding energy among the analysed complexes. Overall, TBFM demonstrated stable binding interactions with all four proteins throughout the simulation period. Breast Cancer Molecular dynamics DFT ADMET Full Text Additional Declarations No competing interests reported. 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-7289669","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":521799320,"identity":"5a9df7f2-e922-468c-8ec6-05fb43a6bf63","order_by":0,"name":"Matheswaran Palanisamy","email":"","orcid":"","institution":"Government Arts College (A)","correspondingAuthor":false,"prefix":"","firstName":"Matheswaran","middleName":"","lastName":"Palanisamy","suffix":""},{"id":521799321,"identity":"dabb82bf-35f3-41e3-be1f-3e94b04a8af4","order_by":1,"name":"Sugan Sundaravadivelu","email":"","orcid":"","institution":"Government College of 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The ADMET profile of TBFM was also assessed, revealing no violations of Lipinski's Rule of Five, indicating favourable drug-like properties. Molecular dynamics simulations were conducted for 100 ns to assess the stability of the protein\u0026ndash;ligand complexes under near-physiological conditions. The root mean square deviation (RMSD) values for all four proteins werelow, suggesting stable complex formation. Principal component analysis (PCA) showed that the 1ZUA complex formed a compact, oval-shaped cluster. Additionally, Molecular Mechanics Poisson\u0026ndash;Boltzmann Surface Area (MMPBSA) calculations estimated the binding free energy of TBFM with each protein, revealing that 2SRC had the highest binding energy among the analysed complexes. 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