Water-soluble N-heterocyclic carbene precursors bearing benzimidazole core: synthesis, characterization, in vitro antioxidant and anticancer studies

Benzimidazole is an important member of the nitrogen-containing heterocyclic ring system since it confers surprisingly good biological properties in medicinal chemistry such as anticancer drug applications. Keeping this in mind, a new series of asymmetrical 1,3-disubstituted benzimidazolium salts were designed and reported. The compounds were synthesized by the reaction of 1-alkylbenzimidazoles with 2-(2-bromoethyl)-1,3-dioxane. The structures of all the compounds were determined using FT-IR, H-1 and C-13 NMR spectroscopy, LC-MS, and elemental analysis. The compounds were used for their antioxidant capacity by commercial kit assay. Further, these were screened for their cytotoxic effect against cell lines including MCF-7, A-549, and L929 using cisplatin as a reference drug. It resulted that the total antioxidant capacity values of the compounds were found to be quite low compared to the trolox equivalent. On the other side, most importantly, two compounds showed remarkable anticancer activity against MCF-7 and A-549 with IC50 values of 18.06 and 20.44 mu g/cm(3), respectively, in comparison with cisplatin (IC50 = 83.11 and 87.80 mu g/cm(3)). Furthermore, most of the compounds were found to be safe on normal L929 fibroblast cells compared to cancer cells (IC50 values for healthy fibroblasts were 142.70-268.37 mu g/cm(3)). Taken together, the newly synthesized compounds containing benzimidazole core can be readily constructed and used as an attractive class of anticancer agents.{graphical abstracts}