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

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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
Issue number14
Early online date26 Jun 2017
Publication statusPublished - 27 Jul 2017


King's Authors


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.

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