Indazole–Pyridine Hybrids: Design, Synthesis, and Biological Evaluation as Possible Anticancer Agents against Breast Cancer Cell Lines

Indazole–Pyridine Hybrids: Design, Synthesis, and Biological Evaluation as Possible Anticancer Agents against Breast Cancer Cell Lines | 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 Indazole–Pyridine Hybrids: Design, Synthesis, and Biological Evaluation as Possible Anticancer Agents against Breast Cancer Cell Lines Kinjal Parmar, Ishan Panchal This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7458469/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 A novel series of (3-amino-5-methyl-1H-indazol-1-yl)(5-substituted-pyridin-3-yl)methanone derivatives (7a–7j) was synthesized and structurally confirmed using IR, NMR, and mass spectrometry. Molecular docking analysis performed with AutoDock identified compound 7c as the most potent binder (–8.7 kcal/mol), surpassing the standard drug Entrectinib. Compounds 7i and 7e also demonstrated favorable interactions, suggesting their potential as lead molecules. Predicted ADME features include high gastrointestinal absorption and minimal inhibition of cytochrome P450 enzymes, leading to good oral availability. In vitro cytotoxicity tests on MCF-7 breast cancer cells demonstrated that compounds 7b and 7c produced strong antiproliferative effects, with 7c achieving up to 64% reduction in cell viability, approaching the efficacy of Adriamycin. Moderate activity was observed in compounds 7d, 7g, and 7i, whereas 7a, 7e, and 7f displayed weak activity. Overall, compounds 7b and 7c emerge as promising candidates for further optimization, with structural elements such as cyclopentyl and halogen substituents contributing significantly to their biological activity. These results provide a foundation for mechanistic exploration and development of new anticancer agents. Indazole–pyridine derivatives Molecular docking MCF-7 cells cytotoxic activity ADME analysis Full Text Additional Declarations No competing interests reported. Supplementary Files supplementarymaterial.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. 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-7458469","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":505560099,"identity":"cbba0851-fcf0-4747-85c0-78a59cbd15e7","order_by":0,"name":"Kinjal Parmar","email":"data:image/png;base64,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","orcid":"","institution":"Parul University","correspondingAuthor":true,"prefix":"","firstName":"Kinjal","middleName":"","lastName":"Parmar","suffix":""},{"id":505560102,"identity":"973eaef1-cc0a-400b-9243-d50faf0a5087","order_by":1,"name":"Ishan Panchal","email":"","orcid":"","institution":"Parul College of Pharmacy and Research, Parul University","correspondingAuthor":false,"prefix":"","firstName":"Ishan","middleName":"","lastName":"Panchal","suffix":""}],"badges":[],"createdAt":"2025-08-26 04:08:21","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7458469/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7458469/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90187952,"identity":"50239d26-c516-402a-b7ce-2e3a688ed458","added_by":"auto","created_at":"2025-08-29 15:01:58","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":657711,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7458469/v1_covered_e8122869-75e8-419e-99c8-229e5133e08e.pdf"},{"id":90017745,"identity":"5fcfadbc-a4e1-4b8e-a17f-0fba8f8c0bad","added_by":"auto","created_at":"2025-08-27 12:21:03","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":1628801,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-7458469/v1/cf28d59a5265c9132c692b18.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Indazole–Pyridine Hybrids: Design, Synthesis, and Biological Evaluation as Possible Anticancer Agents against Breast Cancer Cell Lines","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"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":"Indazole–pyridine derivatives, Molecular docking, MCF-7 cells, cytotoxic activity, ADME analysis","lastPublishedDoi":"10.21203/rs.3.rs-7458469/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7458469/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eA novel series of (3-amino-5-methyl-1H-indazol-1-yl)(5-substituted-pyridin-3-yl)methanone derivatives (7a\u0026ndash;7j) was synthesized and structurally confirmed using IR, NMR, and mass spectrometry. Molecular docking analysis performed with AutoDock identified compound 7c as the most potent binder (\u0026ndash;8.7 kcal/mol), surpassing the standard drug Entrectinib. Compounds 7i and 7e also demonstrated favorable interactions, suggesting their potential as lead molecules. Predicted ADME features include high gastrointestinal absorption and minimal inhibition of cytochrome P450 enzymes, leading to good oral availability. In vitro cytotoxicity tests on MCF-7 breast cancer cells demonstrated that compounds 7b and 7c produced strong antiproliferative effects, with 7c achieving up to 64% reduction in cell viability, approaching the efficacy of Adriamycin. Moderate activity was observed in compounds 7d, 7g, and 7i, whereas 7a, 7e, and 7f displayed weak activity. Overall, compounds 7b and 7c emerge as promising candidates for further optimization, with structural elements such as cyclopentyl and halogen substituents contributing significantly to their biological activity. These results provide a foundation for mechanistic exploration and development of new anticancer agents.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e","manuscriptTitle":"Indazole–Pyridine Hybrids: Design, Synthesis, and Biological Evaluation as Possible Anticancer Agents against Breast Cancer Cell Lines","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-27 11:56:58","doi":"10.21203/rs.3.rs-7458469/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","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}}],"origin":"","ownerIdentity":"1c4e8285-bbc9-46dd-ac51-426b00092b69","owner":[],"postedDate":"August 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-29T14:53:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-27 11:56:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7458469","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7458469","identity":"rs-7458469","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}