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Bacterial FtsZ inhibition by benzo[ d ]imidazole-2-carboxamide derivative with anti-TB activity.

Tejas M DhameliyaRishu TiwariKshitij I PatelSiva Krishna VagoluDulal PandaDharmarajan SriramAsit K Chakraborti
Published in: Future medicinal chemistry (2022)
Aims: The present study aimed to assess the mode of action of previously reported anti- Mycobacterium tuberculosis benzo[ d ]imidazole-2-carboxamides against FtsZ along with their antibacterial potential. Materials & methods: The anti-mycobacterial action of benzo[ d ]imidazole-2-carboxamides against FtsZ was evaluated using inhibition of Bacillus subtilis 168, light scattering assay, circular dichroism spectroscopy, in silico molecular docking and molecular dynamics simulations. Results & conclusion: Three compounds ( 1k , 1o and 1e ) were active against isoniazid-resistant strains. Four compounds ( 1h , 1i , 1o and 4h ) showed >70% inhibition against B. subtilis 168. Compound 1o was the most potent inhibitor (91 ± 5% inhibition) of  B. subtilis 168 FtsZ and perturbed its secondary structure. Molecular docking and molecular dynamics simulation of complexed 1o suggested M. tuberculosis FtsZ as a possible target for antitubercular activity.
Keyphrases
  • molecular docking
  • molecular dynamics simulations
  • mycobacterium tuberculosis
  • pulmonary tuberculosis
  • bacillus subtilis
  • high resolution
  • mass spectrometry
  • adverse drug