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

Authors

ÖZLEM AKGÜL
MÜMİN ALPER ERDOĞAN
DERVİŞ BİRİM
ÇAĞLA KAYABAŞI
CUMHUR GÜNDÜZ
GÜLİZ ARMAGAN

DOI

10.3906/kim-2009-1

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 (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.

Keywords

Apoptosis, Bcl-2 family proteins, caspase-3/9, cytotoxicity, taurine

First Page

1674

Last Page

1693

Recommended Citation

AKGÜL, ÖZLEM; ERDOĞAN, MÜMİN ALPER; BİRİM, DERVİŞ; KAYABAŞI, ÇAĞLA; GÜNDÜZ, CUMHUR; and ARMAGAN, GÜLİZ (2020) "Design, synthesis, cytotoxic activity, and apoptosis inducing effects of 4- and N-substituted benzoyltaurinamide derivatives," Turkish Journal of Chemistry: Vol. 44: No. 6, Article 20. https://doi.org/10.3906/kim-2009-1
Available at: https://journals.tubitak.gov.tr/chem/vol44/iss6/20