Benzimidazole Isosteres of Salicylanilides Are Highly Active Colistin Adjuvants

Multidrug-resistant bacterial infections have become a global threat. We recently disclosed that the known IKK-β inhibitor IMD-0354 and subsequent analogues abrogate colistin resistance in several Gram-negative strains. Herein, we report the activity of a second-generation library of IMD-0354 analog...

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Bibliographic Details
Published in:ACS infectious diseases 2021-12, Vol.7 (12), p.3303-3313
Main Authors: Li, Haoting, Mattingly, Anne E, Jania, Leigh A, Smith, Richard, Melander, Roberta J, Ernst, Robert K, Koller, Beverley H, Melander, Christian
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Benzimidazoles - pharmacology
Colistin - pharmacology
Microbial Sensitivity Tests
Salicylanilides
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Summary:Multidrug-resistant bacterial infections have become a global threat. We recently disclosed that the known IKK-β inhibitor IMD-0354 and subsequent analogues abrogate colistin resistance in several Gram-negative strains. Herein, we report the activity of a second-generation library of IMD-0354 analogues incorporating a benzimidazole moiety as an amide isostere. We identified several analogues that show increased colistin potentiation activity against Gram-negative bacteria.
ISSN:2373-8227
2373-8227
DOI:10.1021/acsinfecdis.1c00463