Design, Synthesis, Characterization, in-silico and in-vitro Evaluation of Novel 2-mercapto Benzimidazole Derivatives Tethered With Isoniazid for the Treatment of Tuberculosis

Design, Synthesis, Characterization, in-silico and in-vitro Evaluation of Novel 2-mercapto Benzimidazole Derivatives Tethered With Isoniazid for the Treatment of Tuberculosis | 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 Design, Synthesis, Characterization, in-silico and in-vitro Evaluation of Novel 2-mercapto Benzimidazole Derivatives Tethered With Isoniazid for the Treatment of Tuberculosis Nayana Ravindra Jawale, B V Suma This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7208033/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract 2-Mercapto benzimidazole derivatives are well-recognized for their diverse pharmacological activities, including anti-tubercular, antimicrobial, anti-ulcer, analgesic, and anticancer properties. Isoniazid, a first-line antitubercular agent, has been extensively used in the treatment of Mycobacterium tuberculosis infections. Based on these insights, the present study aimed to design and synthesize novel 2-mercapto benzimidazole derivatives tethered with isoniazid to explore their potential as anti-tubercular agents.An in-silico approach was employed to evaluate the binding efficiency of the designed molecules with key mycobacterial targets. The top-scoring compounds from molecular docking studies were selected for synthesis. Three derivatives were successfully synthesized via condensation and acetylation reactions. Structural confirmation of the synthesized compounds was carried out using FT-IR, ^1H-NMR, and mass spectrometry. The anti-tubercular activity of the synthesized derivatives was assessed using the agar well diffusion method against Mycobacterium tuberculosis . The results demonstrated that the synthesized compounds exhibited noteworthy anti-tubercular activity, comparable to or exceeding that of isoniazid, indicating their potential as promising lead molecules for further development. 2-Mercapto benzimidazole Isoniazid Anti-tubercular activity Molecular docking Synthesis Characterization Mycobacterium tuberculosis Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 28 Oct, 2025 Reviews received at journal 14 Oct, 2025 Reviews received at journal 13 Oct, 2025 Reviews received at journal 07 Oct, 2025 Reviews received at journal 01 Oct, 2025 Reviewers agreed at journal 01 Oct, 2025 Reviewers agreed at journal 30 Sep, 2025 Reviewers agreed at journal 29 Sep, 2025 Reviewers agreed at journal 29 Sep, 2025 Reviewers agreed at journal 29 Sep, 2025 Reviewers invited by journal 29 Sep, 2025 Editor assigned by journal 28 Aug, 2025 Submission checks completed at journal 28 Aug, 2025 First submitted to journal 28 Aug, 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. 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-7208033","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":527084383,"identity":"f7d95e37-e238-4b51-a2a9-1aada43b71b2","order_by":0,"name":"Nayana Ravindra Jawale","email":"","orcid":"","institution":"MS Ramaiah University of Applied Sciences","correspondingAuthor":false,"prefix":"","firstName":"Nayana","middleName":"Ravindra","lastName":"Jawale","suffix":""},{"id":527084384,"identity":"db738a8e-3399-4b58-a9a8-280b78b9ad0a","order_by":1,"name":"B V 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Tuberculosis\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-chemistry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Chemistry](https://link.springer.com/journal/44371)","snPcode":"44371","submissionUrl":"https://submission.nature.com/new-submission/44371/3","title":"Discover Chemistry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover 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Isoniazid, a first-line antitubercular agent, has been extensively used in the treatment of \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e infections. Based on these insights, the present study aimed to design and synthesize novel 2-mercapto benzimidazole derivatives tethered with isoniazid to explore their potential as anti-tubercular agents.An in-silico approach was employed to evaluate the binding efficiency of the designed molecules with key mycobacterial targets. The top-scoring compounds from molecular docking studies were selected for synthesis. Three derivatives were successfully synthesized via condensation and acetylation reactions. Structural confirmation of the synthesized compounds was carried out using FT-IR, ^1H-NMR, and mass spectrometry. The anti-tubercular activity of the synthesized derivatives was assessed using the agar well diffusion method against \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e. The results demonstrated that the synthesized compounds exhibited noteworthy anti-tubercular activity, comparable to or exceeding that of isoniazid, indicating their potential as promising lead molecules for further development.\u003c/p\u003e","manuscriptTitle":"Design, Synthesis, Characterization, in-silico and in-vitro Evaluation of Novel 2-mercapto Benzimidazole Derivatives Tethered With Isoniazid for the Treatment of Tuberculosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-10 05:30:29","doi":"10.21203/rs.3.rs-7208033/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-28T07:42:25+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-14T08:21:55+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-14T02:48:24+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-07T07:55:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-01T19:08:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"133555947456812009363205733525621867045","date":"2025-10-01T13:15:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"221730877164658450210222510028499953592","date":"2025-09-30T05:49:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"333127383633184833357814136027257684176","date":"2025-09-29T13:12:20+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"199307450465526513705906900614643802641","date":"2025-09-29T12:50:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"177663324156543923761545669774768428059","date":"2025-09-29T11:51:38+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-29T11:33:48+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-28T06:55:37+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-28T06:36:59+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Chemistry","date":"2025-08-28T06:34:15+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-chemistry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Chemistry](https://link.springer.com/journal/44371)","snPcode":"44371","submissionUrl":"https://submission.nature.com/new-submission/44371/3","title":"Discover Chemistry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e69c5f6b-946a-458e-bf3b-b41d761ca825","owner":[],"postedDate":"October 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-17T08:10:41+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-10 05:30:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7208033","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7208033","identity":"rs-7208033","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}