{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:01:51Z","timestamp":1787029311079,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Targeting ABL tyrosine kinase (TK) remains a cornerstone of chronic myeloid leukemia (CML) therapy. Methods: In this study, a series of novel 4-((2-(4-(aryl)thiazol-2-yl)hydrazineylidene)methyl)-N,N-diphenylaniline derivatives (1\u201312) were synthesized through the reaction of 2-(4-(diphenylamino)benzylidene)hydrazine-1-carbothioamide (intermediate A) with substituted 2-bromo-1-arylethanones. Cytotoxic activity was evaluated in K562 CML cells using the MTT assay. The most active compound was further assessed in HL-60 acute myeloid leukemia (AML) cells and healthy peripheral blood mononuclear cells (PBMCs). Apoptosis induction was analyzed by Annexin V\/ethidium homodimer staining, while ABL TK inhibition was determined using the ADP-Glo kinase assay. Molecular docking studies were performed to investigate binding interactions within the ATP-binding site of ABL TK, and pharmacokinetic properties were also predicted. Results: Intermediate A demonstrated superior antiproliferative activity compared to derivatives 1\u201312 and exhibited cytotoxicity comparable to imatinib in K562 cells (IC50 = 6.15 \u00b1 1.26 \u00b5M vs. 5.14 \u00b1 1.44 \u00b5M, respectively). In HL-60 cells, intermediate A showed an IC50 of 12.04 \u00b1 1.70 \u00b5M, similar to imatinib. Notably, intermediate A displayed enhanced selectivity toward K562 cells over PBMCs (SI = 12.9) relative to imatinib (SI = 6.2). The compound significantly induced apoptosis in K562 cells and inhibited ABL TK activity. Docking studies revealed a distinct binding orientation within the ATP-binding pocket of ABL TK. The compound showed acceptable predicted physicochemical and ADME characteristics based on in silico analysis. Conclusions: Intermediate A emerges as a significant anti-CML candidate exhibiting potent cytotoxic, apoptotic, and moderate ABL TK inhibitory activity, together with a favorable selectivity profile.<\/jats:p>","DOI":"10.3390\/ph19030416","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T15:01:07Z","timestamp":1772636467000},"page":"416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Design, Synthesis, and Biological Evaluation of N,N-Diphenylaniline-Based Derivatives as Antiproliferative Agents and ABL TK Inhibitors Against CML"],"prefix":"10.3390","volume":"19","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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"ref_1","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. 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