Bacterial FtsZ Inhibition By Benzo[ <i>d</i> ]imidazole-2-Carboxamide Derivative With anti-TB Activity

Abstract

<b>Aims:</b> The present study aimed to assess the mode of action of previously reported anti-<i>Mycobacterium tuberculosis</i> benzo[<i>d</i>]imidazole-2-carboxamides against FtsZ along with their antibacterial potential. <b>Materials & methods:</b> The anti-mycobacterial action of benzo[<i>d</i>]imidazole-2-carboxamides against FtsZ was evaluated using inhibition of <i>Bacillus subtilis</i> 168, light scattering assay, circular dichroism spectroscopy, <i>in silico</i> molecular docking and molecular dynamics simulations. <b>Results & conclusion:</b> Three compounds (<b>1k</b>, <b>1o</b> and <b>1e</b>) were active against isoniazid-resistant strains. Four compounds (<b>1h</b>, <b>1i</b>, <b>1o</b> and <b>4h</b>) showed >70% inhibition against <i>B. subtilis</i> 168. Compound <b>1o</b> was the most potent inhibitor (91 ± 5% inhibition) of <i>B. subtilis</i> 168 FtsZ and perturbed its secondary structure. Molecular docking and molecular dynamics simulation of complexed <b>1o</b> suggested <i>M. tuberculosis</i> FtsZ as a possible target for antitubercular activity.