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.
Highlights
Since cancer is one of the leading causes of death worldwide, extensive resources have been invested in the development of increasingly potent anticancer agents for clinical use
Of the phenyl (1-4) and sulfonamide (9-12) derivatives prepared in this study, only the chloro‐bearing compounds 2 and 10 exhibited good cytotoxicity with IC50 values of 29.0 and 38.6 μM, respectively
Western Blot analysis revealed that all compounds, except for 7, induced the intrinsic apoptotic pathway by upregulating BAX, caspase-3, and caspase-9, while downregulating Bcl-2 and Bcl-xL expression levels in PANC-1 cell line either after 24 or 48 h
Summary
Since cancer is one of the leading causes of death worldwide, extensive resources have been invested in the development of increasingly potent anticancer agents for clinical use. Studies indicate that cancer cells evade apoptosis by deregulating this process, thereby resulting in increased drug resistance Given this challenging situation, apoptotic proteins have become the prime target for anticancer research [7,8]. No extensive structure–activity relationship studies have been conducted to identify specific biological pathways that can accommodate taurine‐based derivatives [21] This gap in the data prompted us to design and synthesize a group of novel 4-substituted benzoyltaurinamide derivatives and to determine their anticancer activity (Figure 2). The amine moiety was functionalized as an amide with hydrogen-, chloro-, methoxy-, and methyl-substituted benzoic acids, while the sulfonamide groups remained untouched (Figure 3) This derivatization strategy allowed us to systematically study the impact of the sulfonamide and amide functional groups as well as the electronic and steric characteristics of the substituents on the aromatic ring of the benzoyltaurinamide derivatives on the compound’s anticancer activity. The most active compounds were subsequently employed to deduce the molecular mechanisms governing the anticancer activity of this class of compounds
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
