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

Abstract

In this study, a group of 4-substitutedbenzoyltaurinamide derivative was designed, synthesized, and investigated for their anticancer activity against three cancer cell lines and one non-tumorigenic 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 (in SH-SY5Y and MDA-MB-231 cell lines) and 15 (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.

Discovery of Potent Indolyl-Hydrazones as Kinase Inhibitors for Breast Cancer: Synthesis, X-ray Single-Crystal Analysis, and In Vitro and In Vivo Anti-Cancer Activity Evaluation

“…After 48 h, the medium was immediately changed to PBS, the wound gap was examined, and cells-both control and treated-were captured on camera with a digital camera attached to an Olympus microscope. The region where the wound closes was measured [42,43].…”