New benzothiazole-indole-1,2,3-triazole-N-phenylacetamide derivatives as cytotoxic agents: Design, synthesis, and in vitro cytotoxic evaluations

Abstract

A new series of benzothiazole-indole-1,2,3-triazole-N-phenylacetamide derivatives 9a-m was designed through hybridization of potent cytotoxic pharmacophores. The title derivatives were synthesized by simple and efficient reactions, and their anticancer effects were evaluated by 3-(4,5-Dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against three cancer cell lines SUIT-2, MCF-7, and U87-MG from pancreas, breast, and brain tumors, respectively. Most of the newly synthesized compounds demonstrated cytotoxic effects against the studied cell lines, and among these derivatives, compound 9j bearing the dichlorophenyl moiety was the most active one against all the studied cancer cells. In this regard, compound 9j was more potent than the positive control (cisplatin) against MCF-7 and U87-MG cells. Moreover, compounds 9m and 9k were more potent than cisplatin against U87-MG. In addition, alterations in the cell cycle and the induction of apoptosis by the most potent compounds were also evaluated in MCF-7 cells. These assays demonstrated that our new compounds increase the percentage of cells in the G0/G1 phase of the cell cycle and also induce apoptosis in cancer cells. Docking studies showed that compound 9j may have notable interactions with the topoisomerase II alpha enzyme. The findings of this study showed that benzothiazole-indole-1,2,3-triazole-N-phenylacetamide derivatives exhibit promising anticancer activity.