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We modified the carboxylic acid and the aromatic ring of azotochelin using various chemical motifs. We evaluated the cytotoxicity of the compounds against six different cancer cell lines (KB\u20103\u20101, SNB\u201019, MCF\u20107, K\u2010562, SW\u2010620, and NCI\u2212H460) and a non\u2010cancerous cell line (HEK\u2010293). Among the twenty compounds tested, the IC<jats:sub>50<\/jats:sub> values of nine compounds (<jats:bold>14<\/jats:bold>, <jats:bold>32<\/jats:bold>, <jats:bold>35<\/jats:bold>\u2013<jats:bold>40<\/jats:bold>, and <jats:bold>54<\/jats:bold>) were between 0.7 and 2.0\u2005\u03bcM against a lung cancer cell line (NCI\u2212H460). Moreover, several compounds showed good cytotoxicity profile (IC<jats:sub>50<\/jats:sub> &lt;10\u2005\u03bcM) against the tested cancer cell lines. The flow cytometry analysis showed that compounds <jats:bold>36<\/jats:bold> and <jats:bold>38<\/jats:bold> induced apoptosis in NCI\u2212H460 in a dose\u2010dependent manner. The cell cycle analysis indicated that compounds <jats:bold>36<\/jats:bold> and <jats:bold>38<\/jats:bold> significantly arrested the cell cycle at the S phase to block cancer cell proliferation in the NCI\u2212H460\u2005cell line. The study has produced various novel azotochelin analogs that are potentially effective anticancer agents and lead compounds for further synthetic and medicinal chemistry exploration.<\/jats:p>","DOI":"10.1002\/cmdc.202300715","type":"journal-article","created":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T11:30:36Z","timestamp":1712748636000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Chemical Derivatization Leads to the Discovery Of Novel Analogs of Azotochelin, a Natural Siderophore, as Promising Anticancer Agents"],"prefix":"10.1002","volume":"19","author":[{"given":"Nishant M.","family":"Karadkhelkar","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences College of Pharmacy and Health Sciences St. John's University  8000 Utopia Parkway Queens, NY 11439 (S.Y.)"},{"name":"Current affiliation: The Scripps Research Institute  10550\u2005N Torrey Pines Rd. 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