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Tyrosine kinase inhibitors (TKIs), including imatinib and sunitinib, have revolutionized cancer therapy by selectively targeting kinases such as Bcr\u2010Abl1 (CML) and KIT\/PDGFR\u03b1 (GIST), offering substantial clinical benefits. Motivated by their success, 15 hybrid derivatives (\n                    <jats:bold>4a\u2013e<\/jats:bold>\n                    ,\n                    <jats:bold>5a\u2013e<\/jats:bold>\n                    ,\n                    <jats:bold>6a\u2013e<\/jats:bold>\n                    ) based on the isatin\u2013phenylaminopyrimidine pyridine (PAPP) scaffold were designed, synthesized, and evaluated in cell lines with dysregulated tyrosine kinase activity. Among them, compounds\n                    <jats:bold>6b<\/jats:bold>\n                    and\n                    <jats:bold>6e<\/jats:bold>\n                    showed promising cytotoxicity against the K562 cell line (Bcr\u2010Abl1), with CC\u2085\u2080 values of 8.7 and 12.2\u2009\u03bcM, though they also affected WSS\u20101 cells, suggesting limited tumor selectivity. Compound\n                    <jats:bold>4c<\/jats:bold>\n                    displayed strong cytotoxic activity against several solid tumor cell lines, including DU145 (3.9\u2009\u03bcM), MCF7 (3.5\u2009\u03bcM), HT29 (7.7\u2009\u03bcM), NCI\u2010H1299 (19.5\u2009\u03bcM), and T98G (9.0\u2009\u03bcM). Importantly, all tested compounds showed low erythrocytic toxicity (CC\u2085\u2080 &gt;\u200930\u2009\u03bcM).\n                  <\/jats:p>","DOI":"10.1002\/ardp.70240","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T12:54:18Z","timestamp":1778763258000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hybrid Isatin and Imatinib Analogues as Potential Antineoplastic Agents"],"prefix":"10.1002","volume":"359","author":[{"given":"Andressa Paula","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de S\u00edntese de F\u00e1rmacos (Instituto de Tecnologia em F\u00e1rmacos\u2010Farmanguinhos Rio de Janeiro Rio de Janeiro Brazil"},{"name":"Programa de P\u00f3s\u2010gradua\u00e7\u00e3o em Farmacologia e Qu\u00edmica Medicinal Instituto de Ci\u00eancias Biom\u00e9dicas (Centro de Ci\u00eancias da Sa\u00fade Rio de Janeiro Rio de Janeiro 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