Benzimidazole scaffolds as potential anticancer agents: Synthesis and Biological evaluation

Abstract

Cancer continues to be one of the leading causes of mortality worldwide. Current anti‐cancer agents have a major limitation of drug resistance. Continued search for newer and safer anticancer drugs is critical and this led us to synthesize a small library of structurally unique benzimidazoles with anticancer potential. Various analogs of these compounds were derived from indole‐2‐carboxylic acid, fatty acids and alpha amino acids, providing a panel of diverse structures. Synthesized compounds were tested in three different cancer cell lines‐HepG2 (human hepatocellular carcinoma), HeLa (human cervical cancer), A549 (human lung carcinoma) and one transformed cell line HEK293 (human embryonic kidney). Many of the compounds tested induced cytotoxicity in a concentration‐dependent manner. Cell viability studies using MTT assay showed that indole and fatty acid based benzimidazoles were most potent followed by amino acid derivatives. Presence of protective functional groups decreased activity of the compounds. In order to investigate the mechanism of the cytotoxicity of the compounds, cleaved caspase 3 expression was measured and a fluorescence‐based apoptosis‐necrosis assay was performed. These results confirmed the presence of apoptosis process in cell death induced by the benzimidazole compounds. Furthermore, cell cycle alterations accompanied the cell death. In addition to anticancer activity, several of these compounds also showed promising antibacterial activity against S. aureus and S. epidermidis. Taken together, our findings demonstrate that the novel benzimidazole compounds could serve as potential leads for the further development of new anticancer agents.Support or Funding InformationFunding for this research was provided by College of Pharmacy and Health Sciences, St John's University, Queens, NYThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.