Design, synthesis, cytotoxic activity, and apoptosis inducing effects of 4-and N-substituted benzoyltaurinamide derivatives

Authors : Ozlem AKGUL, Mumin Alper ERDOGAN, Dervis BİRİM, Cagla KAYABASİ, Cumhur GUNDUZ, Guliz ARMAGAN

Pages : 1674-1693

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Publication Date : 0000-00-00

Article Type : Research Paper

Abstract :In this study, a group of 4-substituted benzoyltaurinamide derivatives were designed, synthesized, and investigated for their anticancer activity against three cancer cell lines and one nontumorigenic cell line by MTT assay. Among the final compounds, methoxyphenyl derivatives 14, 15, 16 were found to be effective against all the tested cancerous cell lines with promising selectivity. The most active compounds were further evaluated to determine the molecular mechanism of their anticancer activity by using western blot assay and the Annexin V-FITC/PI test. Compound 14 insert ignore into journalissuearticles values(in SH-SY5Y and MDA-MB-231 cell lines); and 15 insert ignore into journalissuearticles values(in SH-SY5Y cell line); were found to induce intrinsic apoptotic pathway by upregulating BAX, caspase-3, and caspase-9, while downregulating Bcl-2 and Bcl-xL expression levels. According to mechanistic studies, compounds displayed their anticancer activity via three different mechanisms: a. caspase-dependent, b. caspase-independent, and c. caspase-dependent pathway that excluded caspase-9 activation. As a result, this study provides interesting data which can be used to design new taurine-based anticancer derivatives.
Keywords : Apoptosis, Bcl 2 family proteins, caspase 3 9, cytotoxicity, taurine