Synthesis and insight into the structure–activity relationships of 2-phenylbenzimidazoles as prospective anticancer agents

Abstract

In order to explore and develop new anticancer agents, three series of 2-phenylbenzimidazoles, 15-46, were condensed under simple and mild conditions using sodium metabisulfite as an oxidation agent and another series, 47-55, were obtained <i>via</i> a reduction reaction using sodium borohydride. All the compounds synthesized were evaluated for their <i>in vitro</i> anticancer activities against three human cancer cell lines. The novel compound 38 was found to be the most potent multi cancer inhibitor against A549, MDA-MB-231, and PC3 cell lines (IC₅₀ values 4.47, 4.68 and 5.50 μg mL^-1, respectively). In addition, compound 40 exhibited the best IC₅₀ value of 3.55 μg mL^-1 against the MDA-MB-231 cell line. The results demonstrated that introducing a new substituent to compounds 37-55 could improve their antiproliferative activities.