{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:24:18Z","timestamp":1788272658228,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014517","name":"Louisiana Biomedical Research Network","doi-asserted-by":"publisher","award":["P2O GM103424\u221220"],"award-info":[{"award-number":["P2O GM103424\u221220"]}],"id":[{"id":"10.13039\/100014517","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,4,14]]},"abstract":"<jats:p>\n                    Colorectal cancer (CRC) remains a major global health challenge, with current therapeutic options often limited by drug resistance and adverse effects. Small molecules provide distinct advantages, including oral bioavailability, cost\u2010effectiveness, and the ability to target intracellular pathways critical for tumor progression. In this study, we designed and synthesized a new series of pyrazolone derivatives with varied substitution patterns using microwave\u2010assisted methods and evaluated their antiproliferative activity against CRC cell lines (HCT\u2010116 and WiDr). Among these, PL\u201013 emerged as a potent and selective candidate, exhibiting strong cytotoxicity toward cancer cells while sparing noncancerous CRL\u20101459 colon cells. Functional assays, including colony formation and wound healing, confirmed its ability to inhibit cell proliferation and migration. Western blot analyses demonstrated that PL\u201013 induces apoptosis via the intrinsic mitochondrial pathway, as evidenced by increased levels of cleaved caspase\u20109 and PARP, and modulates LC3A\/B expression, suggesting involvement of autophagy. Kinome profiling revealed selective binding of PL\u201013 to FLT3, which was validated by an IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 8.2\u2009\u03bcM. Molecular docking further supported these findings, showing favorable binding energy (\u20137.98\u2009kcal\/mol) compared to regorafenib (\u20137.13\u2009kcal\/mol). Collectively, these results highlight PL\u201013 as a promising lead compound for further optimization toward CRC therapy.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500864","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T05:45:23Z","timestamp":1775195123000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pyrazolone Compounds as Promising Anticancer Agents for Colorectal Cancer: Synthesis, Antiproliferative Activity, and Mechanistic Insights"],"prefix":"10.1002","volume":"21","author":[{"given":"Ali","family":"Gholamian Moghaddam","sequence":"first","affiliation":[{"name":"School of Sciences College of Arts Education and Sciences University of Louisiana at Monroe  Monroe Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atchimnaidu","family":"Siriki","sequence":"additional","affiliation":[{"name":"School of Sciences College of Arts 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