Novel benzimidazole-acrylonitrile hybrids and their derivatives: Design, synthesis and antimycobacterial activity

Eur J Med Chem. 2020 Feb 15;188:112010. doi: 10.1016/j.ejmech.2019.112010. Epub 2019 Dec 24.

Abstract

This paper reports the synthesis and evaluation of some benzimidazole-acrylonitrile hybrid derivatives for their in vitro antimycobacterial activities against Mycobacterium tuberculosis H37Rv. Among the derivatives studied, 3b was found to be the most active compound with MIC of 0.78 μg/mL against M. tuberculosis. This is a quite good activity compared with ethambutol (MIC = 1.56 μg/mL). Moreover, 3b showed 2.8 log fold reduction in bacterial count of dormant forms of mycobacterium which is more potent than first line drugs isoniazid, ciprofloxacin, rifampicin and moxifloxacin. Having activities against both active and dormant forms of M. tuberculosis,3b may be a useful candidate for the development of new drugs to treat tuberculosis.

Keywords: Acrylonitrile; Antimycobacterial activity; Benzimidazole; Nutrient starvation test; Propanenitrile.

MeSH terms

  • Acrylonitrile / chemistry
  • Acrylonitrile / pharmacology*
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium tuberculosis / drug effects*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Benzimidazoles
  • benzimidazole
  • Acrylonitrile