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In search of new anti\u2010TB leads, a library of ethyl 5\u2010(1\u2010benzyl\u20101<jats:italic>H<\/jats:italic>\u2010indol\u20105\u2010yl) isoxazole\u20103\u2010carboxylates were generated through a strategy of scaffold hopping from the proven isoxazole\u20103\u2010carboxylate\u2010based anti\u2010TB pharmacophore. We evaluated their antibacterial potential against a panel of pathogenic bacteria and <jats:italic>Mtb H<jats:sub>37<\/jats:sub>Rv<\/jats:italic> strains. The majority of the compounds exhibited notable <jats:italic>in vitro<\/jats:italic> efficacy against the <jats:italic>H<jats:sub>37<\/jats:sub>Rv<\/jats:italic> strains (MIC 0.25 to 16 <jats:italic>\u03bc<\/jats:italic>g\/mL) and were not cytotoxic with a Selectivity Index (SI) &gt;10. Compound <jats:bold>5e<\/jats:bold> (3,4\u2010dichlorobenzyl substituent) was found to be optimally active in the lot (MIC 0.25 <jats:italic>\u03bc<\/jats:italic>g\/mL) and SI &gt;200. It also displayed equipotent activity against drug\u2010resistant <jats:italic>Mtb<\/jats:italic> (DR\u2010<jats:italic>Mtb<\/jats:italic>) strains. In addition, it demonstrated concentration\u2010dependent bactericidal activity in a time\u2010kill kinetic assay similar to first\u2010line anti\u2010TB drugs besides exhibiting synergistic activity with Streptomycin. Moreover, it complies with the drug\u2010likeness characteristic, making it a promising candidate for further exploration as a probable anti\u2010TB lead.<\/jats:p>","DOI":"10.1002\/cmdc.202400902","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T01:02:02Z","timestamp":1735520522000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Design, Synthesis and Biological Evaluation of Ethyl 5\u2010(1\u2010benzyl\u20101<i>H<\/i>\u2010indol\u20105\u2010yl) Isoxazole\u20103\u2010Carboxylates as Antimycobacterial Agents"],"prefix":"10.1002","volume":"20","author":[{"given":"Rani","family":"Bandela","sequence":"first","affiliation":[{"name":"Department of Chemical Sciences National Institute of Pharmaceutical Education and Research (NIPER)  Address 1Balanagar Hyderabad 500037 Telangana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santosh 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