A novel synthesis of 2-arylbenzimidazoles in molecular sieves-MeOH system and their antitubercular activity. Issue 15 (15th August 2018) - Chaturvedi, Amit K.
Graphical abstract: A new synthesis of antitubercular benzimidazoles. Highlights: An efficient and chemoselective new synthetic protocol for arylbenzimidazoles. Three of the diarylbenzimidazoles antitubercular activity against M. tuberculosis H37 RV (MIC = 16, 24 and 67 µM). In molecular docking studies, compounds showed moderate affinity to DNA gyrase of M. tuberculosis . Compound4m showed moderate gyrase supercoiling inhibition activity. Best analogue, 4y was non-toxic in in-vivo acute oral toxicity. Abstract: Arylbenzimidazoles have been synthesized as antimycobacterial agents. An efficient synthesis has been developed for 2-arylbenzimidazoles from o -phenylenediamines and aromatic aldehydes in molecular sieves-methanol system. The methodology is straightforward to get 2-arylbenzimidazoles (3a –3z ) in excellent yields with high chemoselectivity over 2-aryl-1-benzylbenzimidazoles (4a –4z ). All these benzimidazole analogues were evaluated against M. tuberculosis in BACTEC radiometric assay. The compounds4y and4z exhibited potential antitubercular activity against M. tuberculosis H37 RV, MIC at 16 µM and 24 µM respectively. The best compound of the series i.e. compound4y was well tolerated by Swiss-albino mice in acute oral toxicity. Compound4y possessing a diarylbenzimidazole core, can further be optimized for better activity.