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The newly synthesized coumarin\u2010thymidine conjugates (<jats:bold>1a\u2013l<\/jats:bold>) were characterized using IR, NMR, GC\u2010MS, and CHN elemental analysis. The novel conjugates were found to exhibit potent anti\u2010TB activity against the <jats:italic>Mycobacterium tuberculosis<\/jats:italic> H<jats:sub>37<\/jats:sub>Rv strain, with minimum inhibitory concentrations (MIC) of the active compounds ranging between 0.012 and 0.482\u2009\u00b5M. Compound <jats:bold>1k<\/jats:bold> was established as the most active candidate with a MIC of 0.012\u2009\u00b5M. The toxicity study on HEK cells confirmed the nontoxic nature of compounds <jats:bold>1e<\/jats:bold>, <jats:bold>1h<\/jats:bold>, <jats:bold>1i<\/jats:bold>, <jats:bold>1j<\/jats:bold>, and <jats:bold>1k<\/jats:bold>. Also, the most active compounds (<jats:bold>1k<\/jats:bold>, <jats:bold>1j<\/jats:bold>, and <jats:bold>1e<\/jats:bold>) were stable in the pH range from 2.5 to 10, indicating compatibility with the biophysical environment. Based on the p<jats:italic>K<\/jats:italic><jats:sub>a<\/jats:sub> studies, compounds <jats:bold>1k<\/jats:bold>, <jats:bold>1j<\/jats:bold>, and <jats:bold>1e<\/jats:bold> are capable of crossing lipid\u2010membrane barriers and acting on target cells. Molecular docking studies on the <jats:italic>M. tuberculosis<\/jats:italic> \u03b2\u2010oxidation trifunctional enzyme (PDB ID: 7O4V) were conducted to investigate the mechanisms of anti\u2010TB activity. All compounds showed excellent hydrogen binding interactions and exceptional docking scores against <jats:italic>M. tuberculosis<\/jats:italic>, which was in accordance with the results. Compounds <jats:bold>1a\u2013l<\/jats:bold> possessed excellent affinity to proteins, with binding energies ranging from \u22127.4 to \u22128.7\u2009kcal\/mol.<\/jats:p>","DOI":"10.1002\/ardp.202200633","type":"journal-article","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T01:51:21Z","timestamp":1673574681000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Design, synthesis, molecular docking, and biological evaluation of coumarin\u2010thymidine analogs as potent anti\u2010TB agents"],"prefix":"10.1002","volume":"356","author":[{"given":"Dinesh S.","family":"Reddy","sequence":"first","affiliation":[{"name":"Centre for Nano and Material Sciences, Jain (Deemed\u2010to\u2010be\u2010University)  Bangalore Karnataka India"}]},{"given":"Anamika","family":"Sinha","sequence":"additional","affiliation":[{"name":"Centre for Nano and Material Sciences, Jain (Deemed\u2010to\u2010be\u2010University)  Bangalore Karnataka India"}]},{"given":"Mahantesh M.","family":"Kurjogi","sequence":"additional","affiliation":[{"name":"Multi\u2010Disciplinary Research Unit Karnataka Institute of Medical Sciences  Hubli Karnataka India"}]},{"given":"H.","family":"Shanavaz","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Engineering and Technology Jain University  Bangalore Karnataka India"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9760-6233","authenticated-orcid":false,"given":"Amit","family":"Kumar","sequence":"additional","affiliation":[{"name":"Centre for Nano and Material Sciences, Jain (Deemed\u2010to\u2010be\u2010University)  Bangalore Karnataka India"}]}],"member":"311","published-online":{"date-parts":[[2023,1,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202200214"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.41.1.359-367.2003"},{"key":"e_1_2_7_3_1","unstructured":"World Health Organization Global Tuberculosis Report 2019.https:\/\/www.who.int\/publications\/i\/item\/9789241565714"},{"key":"e_1_2_7_3_2","unstructured":"World Health Organization Global Tuberculosis Report 2021.https:\/\/www.who.int\/teams\/global-tuberculosis-programme\/tb-reports\/global-tuberculosis-report-2021"},{"key":"e_1_2_7_3_3","author":"Kamat V.","year":"2022","journal-title":"Arch. 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