Solvent-free strategy for facile synthesis and cytotoxicity evaluation of benzimidazole derivatives

This study reports a facile synthesis and the cytotoxic evaluation of N–H benzimidazoles. This synthetic method made use of the condensation reaction between o-phenylenediamine and benzylamine and was highlighted by its solvent-free reaction conditions and short reaction time with the use of Na2S2O5 as an inexpensive and environmentally friendly oxidizing agent. The cytotoxicity assays revealed that the benzimidazole derivatives 3l, 3h, and 3r displayed strong activity against the HeLa cancer cell line with the IC50 of 1.54 μM, 0.86 μM, and 1.03 μM, respectively, which were 5.6-fold, 10-fold, and 8-fold stronger than the positive control 5-fluorouracil (5-FU, IC50 = 8.61 μM). Furthermore, both compounds 3h and 3r exhibited similar cytotoxicities against MCF-7, which were equivalent to that of 5-FU and about 2.5-fold stronger than 5-FU towards the A549 cell line.