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Herein, a series of pyrazole\u2010sulfonamide derivatives are synthesized and evaluated for inhibition of\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010carbonic anhydrases (MtCA 1 and MtCA 3). N\u2010substituted analogues (\n                    <jats:bold>6a\u20136i<\/jats:bold>\n                    ) are inactive, while compounds bearing a free sulfonamide group (SO\n                    <jats:sub>2<\/jats:sub>\n                    NH\n                    <jats:sub>2<\/jats:sub>\n                    ) (\n                    <jats:bold>5a\u20135s<\/jats:bold>\n                    ) exhibit potent inhibitory activity, with\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>i<\/jats:sub>\n                    values of 0.2154\u20130.7542\u2009\u00b5M for MtCA 1 and 0.0548\u20130.3241\u2009\u00b5M for MtCA 3. Molecular docking studies support their binding interactions and selectivity. Antitubercular screening of all synthesized compounds reveals minimum inhibitory concentration (MIC) values in the range of 4\u2013128\u2009\u00b5g mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    . Among them, compound\n                    <jats:bold>5p<\/jats:bold>\n                    emerges as the most potent derivative, with a\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>i<\/jats:sub>\n                    of 0.07\u2009\u00b5M against MtCA 3 and an MIC of 8\u2009\u00b5g mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    , outperforming the reference inhibitor acetazolamide. It exhibits no cytotoxicity in THP\u20101 cells, showing no toxicity against human cell lines, and demonstrates a favorable selectivity index. Furthermore, compound\n                    <jats:bold>5p<\/jats:bold>\n                    retains activity against rifampicin\u2010resistant\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    . In silico ADMET predictions indicate acceptable pharmacokinetic and safety profiles. These findings suggest that compound\n                    <jats:bold>5p<\/jats:bold>\n                    is a promising lead for the development of novel antitubercular agents, potentially acting through MtCA inhibition.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500633","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T23:20:17Z","timestamp":1760656817000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Exploration of New Pyrazole\u2013Hydrazone\u2013Benzenesulfonamide Conjugates as Potent Mycobacterial Carbonic Anhydrase Inhibitors: Design, Synthesis, and Biological Evaluation"],"prefix":"10.1002","volume":"20","author":[{"given":"Pardeep","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Chemical Sciences National Institute of Pharmaceutical Education and Research (NIPER)  Balanagar Telangana Hyderabad 500037 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1827-9131","authenticated-orcid":false,"given":"Anuradha","family":"Singampalli","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences National Institute of Pharmaceutical Education and Research (NIPER)  Balanagar Telangana Hyderabad 500037 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rani","family":"Bandela","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences National Institute of Pharmaceutical Education and Research (NIPER)  Balanagar Telangana Hyderabad 500037 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sri Mounika","family":"Bellapukonda","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences National Institute of Pharmaceutical Education and Research (NIPER)  Balanagar Telangana Hyderabad 500037 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laxma Naik","family":"Korra","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences National Institute of Pharmaceutical Education and Research (NIPER)  Balanagar Telangana Hyderabad 500037 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramakrishna","family":"Kodi","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences National Institute of Pharmaceutical Education and Research (NIPER)  Balanagar Telangana Hyderabad 500037 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhendu","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences National Institute of Pharmaceutical Education and Research (NIPER)  Balanagar Telangana Hyderabad 500037 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aman","family":"Dalal","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences National Institute of Pharmaceutical Education and Research (NIPER)  Balanagar Telangana Hyderabad 500037 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puja Kumari","family":"Agnivesh","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences National Institute of Pharmaceutical Education and Research (NIPER)  Balanagar Telangana Hyderabad 500037 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankita","family":"Devi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences National Institute of Pharmaceutical Education and Research (NIPER)  Balanagar Telangana Hyderabad 500037 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6671-2022","authenticated-orcid":false,"given":"Srinivas","family":"Nanduri","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences National Institute of Pharmaceutical Education and Research (NIPER)  Balanagar Telangana Hyderabad 500037 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4346-6567","authenticated-orcid":false,"given":"Nitin Pal","family":"Kalia","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences National Institute of Pharmaceutical Education and Research (NIPER)  Balanagar Telangana Hyderabad 500037 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6874-9419","authenticated-orcid":false,"given":"Niccol\u00f2","family":"Paoletti","sequence":"additional","affiliation":[{"name":"Neurofarba Department University of Florence Section of Pharmaceutical Sciences  Via Ugo Schiff 6 Sesto Fiorentino 50019 Florence Italy"},{"name":"Department NEUROFARBA\u2014Pharmaceutical and nutraceutical section Laboratory of Molecular Modeling Cheminformatics &amp; 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