Benzimidazole-based antibacterial agents against Francisella tularensis

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 2-3 log reduction in colony forming units (CFU) per mL at concentrations of 10 and 50 μg/mL.