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Most derivatives demonstrated good-to-moderate cytotoxic profiles. Among them, compound\n                    <jats:bold>6b<\/jats:bold>\n                    emerged as the most potent lead candidate, with a mean IC\n                    <jats:sub>50<\/jats:sub>\n                    of 4.20 \u00b5M, representing a 1.7-fold higher potency than the reference drug, sorafenib (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20096.80 \u00b5M). Specifically, compound\n                    <jats:bold>6b<\/jats:bold>\n                    exhibited enhanced cytotoxicity against HCT-116 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20095.20 \u00b5M) and MCF-7 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20094.20 \u00b5M), and a two-fold higher potency against HepG-2 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20093.20 \u00b5M) cells compared to sorafenib. Enzymatic assays revealed that\n                    <jats:bold>6b<\/jats:bold>\n                    acts as an efficient multi-kinase inhibitor, effectively targeting EGFR (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.058 \u00b5M) and HER-2 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.060 \u00b5M) with potencies comparable or superior to the standard controls erlotinib and lapatinib, while moderately inhibiting VEGFR-2 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.51 \u00b5M). Safety screening against normal WI-38 cells showed low cytotoxicity (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200951.21 \u00b5M) and outstanding selectivity indices (SI\u2009&gt;\u200910, &gt;\u200912, and 16) for HCT-116, MCF-7, and HepG-2, respectively. Mechanistic investigations in HepG-2 cells confirmed that\n                    <jats:bold>6b<\/jats:bold>\n                    induced a 6.9-fold increase in caspase-3\/7 activity, triggering significant apoptosis. SAR analysis highlighted that a 6-methyl substitution on the quinoline core, an unsubstituted N-1 position, and a bulky 3-phenyl group on the thiazole ring are key structural prerequisites for optimal anticancer activity. These findings, along with docking investigation, highlight compound\n                    <jats:bold>6b<\/jats:bold>\n                    as a promising multi-kinase therapeutic scaffold for further targeted oncological optimization.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-69777-9","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:38:36Z","timestamp":1788791916000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, synthesis, and biological evaluation of quinolin-2-one\/thiazole hybrids as multi-targeted antiproliferative agents inducing caspase-dependent apoptosis"],"prefix":"10.1038","volume":"16","author":[{"given":"Lamya H.","family":"Al-Wahaibi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah Yahya Abdullah","family":"Alzahrani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Br\u00e4se","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendawy N.","family":"Tawfeek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahaa G. 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