Synthesis and anticancer activity studies of new thiazole derivatives

In the current work, new thiazolyl hydrazones (2a-p) were synthesized and investigated for their cytotoxic effects on K562 chronic myelogenous leukemia cell line. Among these derivatives, compounds 2h, 2j and 2l showed potent anticancer activity against K562 cell line. Their cytotoxic effects on other leukemia (HL-60, MT-2 and Jurkat) cells and peripheral blood mononuclear cells were determined. In particular, 4-(4-(methylsulfonyl)phenyl)-2-[2-((1,3-benzodioxol-4-yl)methylene)hydrazinyl]thiazole (2j) showed anticancer activity against K562 cell line (IC50= 8.87±1.93 µM) similar to imatinib (IC50= 6.84±1.11 µM) with a high selectivity index (SI>11.27). Compound 2j was also found to be more effective than imatinib on HL-60, Jurkat and MT-2 cells. Due to its selective anticancer activity, compound 2j was investigated for its apoptotic effect on K562 cells and inhibitory effects on eight different tyrosine kinases. Compound 2j induced apoptosis more than imatinib and showed stronge inhibitory activity against ABL1 kinase (IC50= 5.37±1.17 µM). Molecular docking study was conducted to investigate its binding mode into the ATP binding site of ABL1 kinase (PDB code: 1IEP) using MOE 2018.01 program. Compound 2j showed high affinity to the ATP binding site of ABL1 kinase forming strong interactions. The in vitro and in silico studies pointed out the importance of the methylsulfonyl substituent for ABL1 kinase inhibitory activity.