{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:25:04Z","timestamp":1784762704073,"version":"3.55.0"},"reference-count":67,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Anadolu University Scientific Research Projects Coordination Unit","award":["THD-2026-3435"],"award-info":[{"award-number":["THD-2026-3435"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Chronic myeloid leukemia (CML) is primarily associated with the BCR:ABL1 fusion protein. Although tyrosine kinase inhibitors (TKIs) have markedly enhanced treatment outcomes, the development of agents with improved therapeutic characteristics remains necessary. The present work focused on the synthesis of a new series of thiazolone derivatives (F1-11) and the assessment of their anti-CML activity through inhibition of ABL tyrosine kinase (TK). Methods: The designed compounds were prepared through a multistep synthetic pathway involving the formation of a new chalcone intermediate (A), synthesis of a new pyrazoline carbothioamide intermediate (B), and cyclization with different aldehydes to produce the target new thiazolone derivatives (F1-11). Cytotoxic effects were investigated against K562 CML cells using the MTT assay. The lead compound was additionally evaluated in HL-60 AML cells and normal PBMCs. Apoptotic induction was analyzed using Annexin V\/ethidium homodimer staining, whereas ABL TK inhibitory activity was measured through the ADP-Glo assay. Molecular docking studies were conducted to explore ligand interactions within the ATP-binding domain of ABL TK. Results: Among the synthesized molecules, F-4 demonstrated the strongest activity against K562 cells with an IC50 value of 6.85 \u00b5M, close to that observed for imatinib (IC50 = 5.20 \u00b5M). The compound showed reduced cytotoxicity toward HL-60 cells (IC50 = 33.44 \u00b5M) and exhibited favorable selectivity toward PBMCs (SI = 13). Apoptosis studies revealed 51% early apoptotic cells and 43% late apoptotic cells following treatment. In the kinase assay, F-4 inhibited ABL TK activity by 39% at 10 \u00b5M and by 70% at 100 \u00b5M. Docking simulations suggested interactions with residues His361 and Asp381 in addition to nearby hydrophobic amino acids, although the interaction network was less extensive than that of imatinib. Conclusions: The findings identify F-4 as a promising new thiazolone-derived scaffold with selective anti-CML activity and notable ABL TK inhibitory potential. Additional structural optimization may further enhance its binding characteristics and therapeutic efficacy.<\/jats:p>","DOI":"10.3390\/pharmaceutics18060709","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:50:58Z","timestamp":1781157058000},"page":"709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting ABL Tyrosine Kinase in Chronic Myeloid Leukemia: Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Thiazolone Derivatives"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4847-9711","authenticated-orcid":false,"given":"Belgin","family":"Sever","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, T\u00fcrkiye"},{"name":"Department of Molecular Biology and Genetics, Burdur Mehmet Akif Ersoy University, Istiklal Campus, Burdur 15200, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9796-7669","authenticated-orcid":false,"given":"Halilibrahim","family":"Ciftci","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Burdur Mehmet Akif Ersoy University, Istiklal Campus, Burdur 15200, T\u00fcrkiye"},{"name":"Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bavaro, L., Martelli, M., Cavo, M., and Soverini, S. 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