Studies on some new 2-substituted-1H-benzimidazole derivatives

In this study, 12 (1 of registered in the literature) 2-(1H-benzo[d]imidazol-2-yl)-3-(4-(4-substitutedpiperazin-1-yl)phenyl)acrylonitrile (3a-l) and 3 2-(1H-benzo[d]imidazol-2-yl)-3-(4-(4-substitutedpiperazin-1-yl)phenyl)propanenitrile (4a, b and f) was synthesized and their antimycobacterial activity were investigated. The target compounds 2-(1H-benzo[d]imidazol-2-yl)-3-(4-(4-substitutedpiperazin-1-yl)phenyl)acrylonitrile (3a-l) was obtained by condensation of 2-(1H-benzo[d]imidazol-2-yl)acetonitrile (1) and 4-(4-substitutedpiperazine)benzaldehydes (2a-l). 2-(1H-benzo[d]imidazol-2-yl)-3-(4-(4-substitutedpiperazin-1-yl)phenyl)propanenitriles (4a, b and f) were obtained by reduction of acrylonitriles with sodium borohydride. The chemical structures of these compounds were determined by IR, 1H-NMR, 13C-NMR, mass spectroscopy and elemental analysis methods. The in vitro activities of the target compounds against M. tuberculosis H37Rv were tested comparatively with isoniazide, rifampicin and ethambutol. It was observed that 2-(1H-benzo[d]imidazol-2-yl)-3-(4-(4-(4-methylphenyl)piperazin-1-yl)phenyl)acrylonitrile (3b) was the most active derivative of the series with MIC value of 0.78 µg / mL against M. tuberculosis and had higher antimycobacterial activity than ethambutol (MIC = 1.56 μg / mL). In addition, this compound was found to be more active in the nutrition starvation model experiment than isoniazid, ciprofloxacin, rifampicin and moxifloxacin, which are reference drugs against M. tuberculosis. Based on these results, 3b is thought to be a promising compound to combat the active and latent forms of M. tuberculosis.