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Structure-activity relationship studies on 2,5,6-trisubstituted benzimidazoles targeting Mtb-FtsZ as antitubercular agents.

ABSTRACT: Filamenting temperature sensitive protein Z (FtsZ) is an essential bacterial cell division protein and a promising target for the development of new antibacterial therapeutics. As a part of our ongoing SAR studies on 2,5,6-trisubstituted benzimidazoles as antitubercular agents targeting Mtb-FtsZ, a new library of compounds with modifications at the 2 position was designed, synthesized and evaluated for their activity against Mtb-H37Rv. This new library of trisubstituted benzimidazoles exhibited MIC values in the range of 0.004-50 μg mL^-1. Compounds 6b, 6c, 20f and 20g showed excellent growth inhibitory activities ranging from 0.004-0.08 μg mL^-1. This SAR study has led to the discovery of a remarkably potent compound 20g (MIC 0.0039 μg mL^-1; normalized MIC 0.015 μg mL^-1). Our 3DQSAR model predicted 20g as the most potent compound in the library.

SUBMITTER: Haranahalli K

PROVIDER: S-EPMC8132993 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Novel trisubstituted benzimidazoles, targeting Mtb FtsZ, as a new class of antitubercular agents.

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