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.