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

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 -FtsZ, a new...

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Published in:MedChemComm 2021-01, Vol.12 (1), p.78-94
Main Authors: Haranahalli, Krupanandan, Tong, Simon, Kim, Saerom, Awwa, Monaf, Chen, Lei, Knudson, Susan E, Slayden, Richard A, Singleton, Eric, Russo, Riccardo, Connell, Nancy, Ojima, Iwao
Format: Article
Language:English
Subjects:
Antiinfectives and antibacterials
Antitubercular agents
Benzimidazoles
Cell division
Chemistry
Drug development
Intermediates
Libraries
Minimum inhibitory concentration
NMR
Nuclear magnetic resonance
Proteins
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Summary: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 -FtsZ, a new library of compounds with modifications at the 2 position was designed, synthesized and evaluated for their activity against -H37Rv. This new library of trisubstituted benzimidazoles exhibited MIC values in the range of 0.004-50 μg mL . Compounds , , and showed excellent growth inhibitory activities ranging from 0.004-0.08 μg mL . This SAR study has led to the discovery of a remarkably potent compound (MIC 0.0039 μg mL ; normalized MIC 0.015 μg mL ). Our 3DQSAR model predicted as the most potent compound in the library.
ISSN:2632-8682
2040-2503
2632-8682
2040-2511
DOI:10.1039/d0md00256a