Bacterial FtsZ inhibition by benzo[<i>d</i>]imidazole-2-carboxamide derivative with anti-TB activity
Dhameliya TM, Tiwari R, Patel KI, Vagolu SK, Panda D, Sriram D, Chakraborti AK
Future medicinal chemistry · 2022-09
Abstract
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.
MeSH terms
- Humans
- Mycobacterium tuberculosis
- Tuberculosis
- Isoniazid
- Imidazoles
- Bacterial Proteins
- Antitubercular Agents
- Microbial Sensitivity Tests
- Molecular Docking Simulation