Design,synthesis, and biological evaluation of novel benzimidazole derivatives and their interaction with calf thymus DNA and synergistic effects with clinical drugs

A series of new benzimidazole derivatives was synthesized and characterized by IR, ¹H NMR, ¹³C NMR, MS, and HRMS spectra. All the new compounds were screened for their antimicrobial activities in vitro by a twofold serial dilution technique. The bioactive evaluation showed that 3,5-bis(trifluoromethyl)phenyl benzimidazoles were comparably or even more strongly antibacterial and antifungal than the reference drugs Chloromycin, Norfloxacin, and Fluconazole. The combination of 2,4-difluorobenzyl benzimidazole derivative 5l and its hydrochloride 7 respectively with the antibacterials Chloromycin, Norfloxacin, and the antifungal Fluconazole was more sensitive to methicillin-resistant MRSA and Fluconazole-insensitive A. flavus. In addition, the interaction of compound 5l with calf thymus DNA demonstrated that this compound could effectively intercalate into DNA to form a compound 5l-DNA complex that might block DNA replication and thereby exert good antimicrobial activity.