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 analogues incorporating a benzimidazole moiety as an amide isostere. We identified several analogues that show increased colistin potentiation activity against Gram-negative bacteria.