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Based on a previously reported lead compound, iCRT14, a series of 2,4\u2010thiazolidinedione derivatives were designed, synthesized, and evaluated in vitro for their antiproliferative activity against colon cancer cells. Compound <jats:bold>15k<\/jats:bold> exhibited the most potent activity against the HCT116 and SW480 cell lines. Compound <jats:bold>15k<\/jats:bold> inhibited Wnt\/\u03b2\u2010catenin signaling by disrupting the protein\u2013protein interactions between \u03b2\u2010catenin and TCF4. Compound <jats:bold>15k<\/jats:bold> simultaneously inhibited tubulin polymerization, disorganized the microtubule network, and arrested the cell cycle at the G2\/M phase, offering an additional mechanism of action and <jats:bold>15k<\/jats:bold> induced cell apoptosis by activating caspase\u20103 and poly(ADP\u2010ribose) polymerase. Additionally, compound <jats:bold>15k<\/jats:bold> inhibited cell migration without affecting the levels of \u03b2\u2010catenin protein. These results offer guidance for developing the current series as potential new anticancer therapeutics.<\/jats:p>","DOI":"10.1002\/ardp.202400796","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T04:29:12Z","timestamp":1741753752000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Discovery of a novel 2,4\u2010thiazolidinedione derivative as dual inhibitor of \u03b2\u2010catenin\/TCF4 interaction and tubulin polymerization in colon cancer cells"],"prefix":"10.1002","volume":"358","author":[{"given":"Yating","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, Xiangya School of Pharmaceutical Sciences Central South University  Changsha Hunan China"},{"name":"Hunan Key Laboratory of Small Molecules for Diagnosis and Treatment of Chronic Disease  Changsha Hunan 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