Open AccessStructure–activity relationship studies on 2,5,6-trisubstituted benzimidazoles targeting Mtb-FtsZ as antitubercular agents
Author(s) -
Krupanandan Haranahalli,
Simon Tong,
Saerom Kim,
Monaf Awwa,
Lei Chen,
Susan E. Knudson,
Richard A. Slayden,
Eric Singleton,
Riccardo Russo,
Nancy Connell,
Iwao Ojima
Publication year - 2021
Publication title -
rsc medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.754
H-Index - 55
ISSN - 2632-8682
DOI - 10.1039/d0md00256a
Subject(s) - ftsz , bacterial cell structure , cell division , bacterial protein , chemistry , microbiology and biotechnology , bacteria , computational biology , biology , cell , biochemistry , genetics , gene
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.