Benzimidazole-based antibacterial agents against Francisella tularensis

Bioorg Med Chem. 2013 Jun 1;21(11):3318-26. doi: 10.1016/j.bmc.2013.02.059. Epub 2013 Apr 3.

Abstract

Francisella tularensis is a highly virulent pathogenic bacterium. In order to identify novel potential antibacterial agents against F. tularensis, libraries of trisubstituted benzimidazoles were screened against F. tularensis LVS strain. In a preliminary screening assay, remarkably, 23 of 2,5,6- and 2,5,7-trisubstituted benzimidazoles showed excellent activity exhibiting greater than 90% growth inhibition at 1 μg/mL. Among those hits, 21 compounds showed MIC90 values in the range of 0.35-48.6 μg/mL after accurate MIC determination. In ex vivo efficacy assays, four of these compounds exhibited 2-3log reduction in colony forming units (CFU) per mL at concentrations of 10 and 50 μg/mL.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / pharmacology*
  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / pharmacology*
  • Cell Line
  • Francisella tularensis / drug effects*
  • Francisella tularensis / growth & development
  • High-Throughput Screening Assays
  • Macrophages / drug effects*
  • Macrophages / microbiology
  • Mice
  • Microbial Sensitivity Tests
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Benzimidazoles
  • Small Molecule Libraries