Novel benzo[4,5]thiazolo[2,3-C][1,2,4]triazoles: Design, synthesis, anticancer evaluation, kinase profiling and molecular docking study

Abstract

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.