Dokla, EME, Abutaleb, NS, Milik, SN et al. (8 more authors) (2020) Development of benzimidazole-based derivatives as antimicrobial agents and their synergistic effect with colistin against gram-negative bacteria. European Journal of Medicinal Chemistry, 186. 111850. ISSN 0223-5234
Abstract
Gram-negative bacteria pose a distinctive risk worldwide, especially with the evolution of major resistance to carbapenems, fluoroquinolones and colistin. Therefore, development of new antibacterial agents to target Gram-negative infections is of utmost importance. Using phenotypic screening, we synthesized and tested thirty-one benzimidazole derivatives against E. coli JW55031 (TolC mutant strain). Compound 6c showed potent activity with MIC value of 2 μg/ml, however, it lacked activity against several Gram-negative microbes with intact efflux systems, including E. coli BW25113 (wild-type strain). Combination of 6c with colistin partially restored its antibacterial activity against wild strains (MIC range, 8–16 μg/ml against E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa). 6c exhibited no cytotoxicity against two mammalian cell lines. Therefore, compound 6c represents a promising lead for further optimization to overcome Gram-negative resistance alone or in combination therapy.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Benzimidazole; Gram-negative bacteria; Phenotypic screening; Antimicrobial resistance; Antibiotic synergy |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 28 Nov 2019 15:55 |
Last Modified: | 07 Feb 2020 16:27 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.ejmech.2019.111850 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:153967 |