Abstract
•Some benzo[4,5]thiazolo[2,3-c][1,2,4]triazole-based derivatives were synthesized.•The cytotoxicity of compounds 8-12 was investigated against three cancer cell lines.•Compound 12 was the most active against cancer cell growth (IC50 = 2.40 - 3.53 μM).•Compound 12 caused 3-4 times induction in caspase 3/7 in A549 cells.•Compound 12 displayed moderate inhibitory activity against EGFR and LCK kinases.•Docking study of compounds 8-12 into EGFR/LCK kinases was performed.
In the current study, we report the synthesis and cytotoxic evaluation of a new series of S-benzo[4,5]thiazolo[2,3-c][1,2,4]triazole-based derivatives 8-12. Cytotoxicity of the new compounds was investigated in A549, MCF-7, and Hep3B cancer cell lines. Among these derivatives, compound 12 bearing an isatin moiety was the most active derivative (IC50 = 2.40-3.53 µM). A mechanistic study of compound 12 was performed using the kinase profiling test to explore its inhibitory activity against 10 types of the oncogenic kinases and the potential activation of caspase 3/7 enzymes. The results revealed that compound 12 showed moderate inhibition of the EGFR and LCK kinases. Moreover, compound 12 also activated caspase-3/7 in A549 cells. The docking study of compound 12 into EGFR ATP-active site revealed that it fits nicely with good binding affinity. Together, the results indicated that compound 12 could serve as a good lead for developing new potential anticancer agents.
[Display omitted]