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Bacterial FtsZ inhibition by benzo[d]imidazole-2-carboxamide derivative with anti-TB activity
Journal
Future Medicinal Chemistry
ISSN
17568919
Date Issued
2022-10-01
Author(s)
Dhameliya, Tejas M.
Tiwari, Rishu
Patel, Kshitij I.
Vagolu, Siva Krishna
Panda, Dulal
Sriram, Dharmarajan
Chakraborti, Asit K.
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.
Subjects