King's College London

Research portal

Triaryl Benzimidazoles as a New Class of Antibacterial Agents against Resistant Pathogenic Microorganisms

Research output: Contribution to journalArticle

Pietro Picconi, Charlotte Hind, Shirin Jamshidi, Kazi Nahar, Melanie Clifford, Matthew E. Wand, J. Mark Sutton, Khondaker Mirazur Rahman

Original languageEnglish
Pages (from-to)6045-6059
Number of pages15
JournalJournal of Medicinal Chemistry
Volume60
Issue number14
Early online date26 Jun 2017
DOIs
Publication statusPublished - 27 Jul 2017

Documents

King's Authors

Abstract

A new class of nontoxic triaryl benzimidazole compounds, derived from existing classes of DNA minor groove binders, were designed, synthesized, and evaluated for their antibacterial activity against multidrug resistant (MDR) Gram-positive and Gram-negative species. Molecular modeling experiments suggest that the newly synthesized class cannot be accommodated within the minor groove of DNA due to a change in the shape of the molecules. Compounds 8, 13, and 14 were found to be the most active of the series, with MICs in the range of 0.5–4 μg/mL against the MDR Staphylococci and Enterococci species. Compound 13 showed moderate activity against the MDR Gram-negative strains, with MICs in the range of 16–32 μg/mL. Active compounds showed a bactericidal mode of action, and a mechanistic study suggested the inhibition of bacterial gyrase as the mechanism of action (MOA) of this chemical class. The MOA was further supported by the molecular modeling study.

Download statistics

No data available

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454