Electrostatic Potential Mapped onto Electron Density Surface, ADME, Molecular Docking and Molecular Dynamics Simulations of Some Indolin-2-one Analogues as Cytochrome C Peroxidase Inhibitors

Electrostatic Potential Mapped onto Electron Density Surface, ADME, Molecular Docking and Molecular Dynamics Simulations of Some Indolin-2-one Analogues as Cytochrome C Peroxidase Inhibitors | 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 Electrostatic Potential Mapped onto Electron Density Surface, ADME, Molecular Docking and Molecular Dynamics Simulations of Some Indolin-2-one Analogues as Cytochrome C Peroxidase Inhibitors Ifeanyi E Otuokere This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4200649/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 The transfer of cytochrome c (cyt c) from the mitochondria to the cytosol is commonly regarded as the final stage in the mitochondria-mediated apoptotic response, where there is no possibility of intervention. A potential approach for the development of antiapoptotic medicines involves the inhibition of cyt c interactions. Therefore, it is necessary to develop more effective pharmaceuticals that can inhibit the functioning of cytochrome c peroxidase. The PyRx virtual screening programme was used to conduct a molecular docking investigation on five indolin-2-one (IDL) analogues as inhibitors of cytochrome c peroxidase. The study on ADME was conducted via the SWISSADME server. The Schrondinger suite was utilized to do molecular dynamics (MD) analysis. The binding affinity of the five IDL analogues were − 14.0 to − 15.1 Kcal/mol. The interactions with the receptor (2X08) were facilitated through various mechanisms, including hydrophobic interactions, salt bridges, hydrogen bonds, π-stacking, and electrostatic bonds. These interactions were facilitated by the presence of specific amino acid residues, namely TRP 51A, PHE 158A, LEU 171A, ALA 174A, PHE 266A, PHE 266A, and LEU 239. The present study made predictions for the ADME features of the substances under investigation, revealing favourable pharmacokinetic characteristics. The study additionally predicted the drug-like characteristics of the compounds and determines their oral bioavailability, indicating favourable bioavailability ratings. The molecular dynamics simulations demonstrated the high stability of the optimal IDL analogue with the 2X08 binding pocket. It was concluded that these compounds could be used as potential drugs for the inhibition of cytochrome c peroxidase. ADME cytochrome c peroxidase docking hydrazones indolin-2-one 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. 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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-4200649","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":286441649,"identity":"b66207e6-443b-47b1-a3a5-e25a71c4e8ae","order_by":0,"name":"Ifeanyi E Otuokere","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBElEQVRIiWNgGAWjYBACNuYDIEoCRDCDCDkQceABPi1sCRAtPFAtxmAtCXitgcrCtCQ2gEh8WvjYmA9+LmyzkLOXSD5s8HGPTfr8sMMPgbbYyek24HIYW7L0zDYJYx6JtOTEGc/ScjfeTjMAakk2NjuAQ4t8j4E0b5tEYo9EjvFhngOHczfOTgBpOZC4DZcWNv7Pv+Fa/hz4n244O/0DAS08bHBbkhkOHEiQl84hZAubmTXPOaBfzjxLNuw5kGy4QTqn4ECCAW6/yLcxP77NU1Ynx96efFjixwE7efnZ6Zs/fKiwk8OlBQwY2ZA4BmCVBniUg8EfZHsbCKkeBaNgFIyCkQYApZBZi3O0+N8AAAAASUVORK5CYII=","orcid":"","institution":"Michael Okpara University of Agriculture","correspondingAuthor":true,"prefix":"","firstName":"Ifeanyi","middleName":"E","lastName":"Otuokere","suffix":""}],"badges":[],"createdAt":"2024-04-01 12:30:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4200649/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4200649/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54878851,"identity":"8c2af52a-ba82-4bbb-a7ab-2f153103b9fc","added_by":"auto","created_at":"2024-04-18 04:07:56","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":699549,"visible":true,"origin":"","legend":"","description":"","filename":"itohowoadme.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4200649/v1_covered_f22e6c17-eb36-4713-b420-3418d2696715.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Electrostatic Potential Mapped onto Electron Density Surface, ADME, Molecular Docking and Molecular Dynamics Simulations of Some Indolin-2-one Analogues as Cytochrome C Peroxidase Inhibitors","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"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":"ADME, cytochrome c peroxidase, docking, hydrazones, indolin-2-one","lastPublishedDoi":"10.21203/rs.3.rs-4200649/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4200649/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe transfer of cytochrome c (cyt c) from the mitochondria to the cytosol is commonly regarded as the final stage in the mitochondria-mediated apoptotic response, where there is no possibility of intervention. A potential approach for the development of antiapoptotic medicines involves the inhibition of cyt c interactions. Therefore, it is necessary to develop more effective pharmaceuticals that can inhibit the functioning of cytochrome c peroxidase. The PyRx virtual screening programme was used to conduct a molecular docking investigation on five indolin-2-one (IDL) analogues as inhibitors of cytochrome c peroxidase. The study on ADME was conducted via the SWISSADME server. The Schrondinger suite was utilized to do molecular dynamics (MD) analysis. The binding affinity of the five IDL analogues were \u0026minus;\u0026thinsp;14.0 to \u0026minus;\u0026thinsp;15.1 Kcal/mol. The interactions with the receptor (2X08) were facilitated through various mechanisms, including hydrophobic interactions, salt bridges, hydrogen bonds, π-stacking, and electrostatic bonds. 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