A novel synthesis of 2-arylbenzimidazoles in molecular sieves-MeOH system and their antitubercular activity

Bioorg Med Chem. 2018 Aug 15;26(15):4551-4559. doi: 10.1016/j.bmc.2018.07.049. Epub 2018 Aug 1.

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 compounds 4y and 4z exhibited potential antitubercular activity against M. tuberculosis H37RV, MIC at 16 µM and 24 µM respectively. The best compound of the series i.e. compound 4y was well tolerated by Swiss-albino mice in acute oral toxicity. Compound 4y possessing a diarylbenzimidazole core, can further be optimized for better activity.

Keywords: Acute oral toxicity; Antitubercular; Arylbenzimidazoles; Chemoselectivity; DNA gyrase; Molecular sieves.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antitubercular Agents / chemical synthesis*
  • Antitubercular Agents / pharmacology
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Body Weight / drug effects
  • DNA Gyrase / chemistry
  • DNA Gyrase / metabolism
  • Imidazoles / chemistry*
  • Imidazoles / pharmacology
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Mycobacterium tuberculosis / drug effects*
  • Protein Structure, Tertiary
  • Structure-Activity Relationship

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • Imidazoles
  • DNA Gyrase