Design, Synthesis and Antimycobacterial Activity of 2-(Benzimidazol-2-yl)-3-(4-(4-substitutedpiperazin-1-yl)phenyl) propanenitrile Analogs

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Tan O. U., Sirim M. M., Krishna V. S., Dharmarajan S.

Hacettepe University Journal of the Faculty of Pharmacy, vol.42, no.2, pp.83-92, 2022 (Scopus) identifier

  • Publication Type: Article / Article
  • Volume: 42 Issue: 2
  • Publication Date: 2022
  • Doi Number: 10.52794/hujpharm.1029943
  • Journal Name: Hacettepe University Journal of the Faculty of Pharmacy
  • Journal Indexes: Scopus
  • Page Numbers: pp.83-92
  • Keywords: antimycobacterial activity, benzimidazole, lysine epsilon aminotransferase, nutrient starvation, propanenitrile, tuberculosis
  • Hacettepe University Affiliated: Yes


© 2022, Hacettepe University, Faculty of Pharmacy. All rights reserved.This paper reports the synthesis and evaluation of six new 2-(benzimidazol-2-yl)-3-(4-(4-substitutedpiperazin-1-yl)phenyl)propanenitrile derivatives (4a-f) for their in vitro antimycobacterial activities against Mycobacterium tuberculosis H37Rv. The target compounds (4a-f) were characterized using IR, 1H and 13C NMR, mass spectral data as well as elemental analysis. Among them, 4c (2-(1H-benzo[d]imidazol-2-yl)-3-(4-(4-(2-chlorophenyl)piperazin-1-yl)phenyl)pro-panenitrile) was found to be the most active compound with MIC of 1.56 μg/mL against M. tuberculosis. In addition, 4c showed 2.1 log reduction against nutrient starved M. tuberculosis which is more potent than first line drugs. Based on their predicted physicochemical values, the compounds obeyed the Lipinski’s “rule of five,” and TPSA/nROT limits. Molecular docking studies were performed to estimate the orientation of 4c at the active site of M. tuberculosis LAT enzyme. These results suggest that 4c may be a good candidate for drug development owing to potential against both active and dormant forms of M. tuberculosis.