{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T23:29:12Z","timestamp":1779233352607,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2025,11,6]]},"abstract":"<jats:p>\n                    Despite significant advancements in antituberculosis (TB) drug discovery, considerable scope remains for novel therapeutic development. Molecular hybridization represents a promising strategy for generating new anti\u2010TB agents. In this study, in\u2009silico molecular docking is employed to design novel isoniazid\u2013sulfonamide hybrids connected via a hydrazone bridge, designated as series\n                    <jats:bold>7j\u2013r<\/jats:bold>\n                    and\n                    <jats:bold>8a\u2013i<\/jats:bold>\n                    . Docking analysis reveals that these compounds interact significantly with the active site of InhA, particularly engaging the catalytic triad residues Y158, F149, and K165, as well as the cofactor NAD. Subsequently, both series are synthesized and evaluated against\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    . Generally, compounds from both series (\n                    <jats:bold>7<\/jats:bold>\n                    and\n                    <jats:bold>8)<\/jats:bold>\n                    exhibit enhanced activity compared to their precursors. Notably, compound\n                    <jats:bold>8a<\/jats:bold>\n                    demonstrated approximately twofold greater potency ( minimum inhibitory concentration (MIC)\u2009=\u20090.156\u2009\u00b5g\u2009mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) with respect to compound\n                    <jats:bold>7j<\/jats:bold>\n                    (MIC\u2009=\u20090.313\u2009\u00b5g\u2009mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    ). However, these compounds lose efficacy against INH\u2010resistant\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    strains harboring\n                    <jats:italic>katG<\/jats:italic>\n                    mutations and remain ineffective against multidrug\u2010resistant and extensively drug\u2010resistant strains of\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    . Encouragingly, the tested compounds exhibit little cytotoxicity against the THP\u20101 human monocytic cell line at a concentration of 20\u2009\u00b5g\u2009mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    . Additionally, the structural stability studies using\n                    <jats:sup>1<\/jats:sup>\n                    H NMR confirm the structural integrity of these compounds. Overall, these molecular hybrids are promising for further development as anti\u2010TB agents after relevant structural optimizations.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500398","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T01:36:44Z","timestamp":1758159404000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Rational Design and Antimycobacterial Evaluation of Aryl Sulfonamide\u2013Linked Isoniazid Hydrazones Against\n                    <i>Mycobacterium Tuberculosis<\/i>"],"prefix":"10.1002","volume":"20","author":[{"given":"Mukanda Gedeon","family":"Kadima","sequence":"first","affiliation":[{"name":"Discipline of Pharmaceutical Sciences Westville Campus University of KwaZulu\u2010Natal  Durban 4000 South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahil","family":"Mishra","sequence":"additional","affiliation":[{"name":"School of Chemistry and Physics University of KwaZulu\u2010Natal  P\/Bag X54001, Westville Durban 4000 South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gobind","family":"Kumar","sequence":"additional","affiliation":[{"name":"School of Chemistry and Physics University of KwaZulu\u2010Natal  P\/Bag X54001, Westville Durban 4000 South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pule","family":"Seboletswe","sequence":"additional","affiliation":[{"name":"School of Chemistry and Physics University of KwaZulu\u2010Natal  P\/Bag X54001, Westville Durban 4000 South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afsana","family":"Kajee","sequence":"additional","affiliation":[{"name":"Department of Microbiology National Health Laboratory Services (NHLS) Inkosi Albert Luthuli Central Hospital  Durban 4000 South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"Ankit","sequence":"additional","affiliation":[{"name":"School of Chemistry and Physics University of KwaZulu\u2010Natal  P\/Bag X54001, Westville Durban 4000 South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fran\u00e7oise","family":"Roquet\u2010Ban\u00e8res","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique UMR 9004 Institut de Recherche en Infectiologie de Montpellier (IRIM) Universit\u00e9 de Montpellier  1919 route de Mende 34293 Montpellier France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u00eblle","family":"Foubert","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique UMR 9004 Institut de Recherche en Infectiologie de Montpellier (IRIM) Universit\u00e9 de Montpellier  1919 route de Mende 34293 Montpellier France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Kremer","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique UMR 9004 Institut de Recherche en Infectiologie de Montpellier (IRIM) Universit\u00e9 de Montpellier  1919 route de Mende 34293 Montpellier France"},{"name":"INSERM IRIM  34293 Montpellier France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1247-5754","authenticated-orcid":false,"given":"Rajshekhar","family":"Karpoormath","sequence":"additional","affiliation":[{"name":"Discipline of Pharmaceutical Sciences Westville Campus University of KwaZulu\u2010Natal  Durban 4000 South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6742-6389","authenticated-orcid":false,"given":"Parvesh","family":"Singh","sequence":"additional","affiliation":[{"name":"School of Chemistry and Physics University of KwaZulu\u2010Natal  P\/Bag X54001, Westville Durban 4000 South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.943545"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2024.107325"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.105242"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiph.2021.01.005"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23102583"},{"key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"a017863","DOI":"10.1101\/cshperspect.a017863","volume":"5","author":"Seung K. 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