Discovery of antitubercular 2,4-diphenyl-1H-imidazoles from chemical library repositioning and rational design

Eur J Med Chem. 2015 Jul 15:100:44-9. doi: 10.1016/j.ejmech.2015.05.048. Epub 2015 Jun 5.

Abstract

TB, caused by Mycobacterium tuberculosis, is one of the deadliest infections worldwide. The co-infection with HIV and the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains have further increased the burden for this disease. In the attempt to respond to the constant need of novel therapeutic options, we herein report the discovery of 2,4-diphenyl-1H-imidazoles as effective antitubercular agents, with MIC in the low micromolar range against actively replicating and persistent M. tuberculosis strains. The good activity, along with the lack of toxicity and the feasible synthesis, underscore their value as novel scaffolds for the development of new anti-TB drugs.

Keywords: Drug-repositioning; Imidazoles; Latent tuberculosis; Multidrug-resistance; Tuberculosis.

MeSH terms

  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Discovery*
  • Drug Repositioning*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects*
  • Structure-Activity Relationship
  • Tuberculosis, Multidrug-Resistant / drug therapy*

Substances

  • Antitubercular Agents