Benzimidazole Isosteres of Salicylanilides Are Highly Active Colistin Adjuvants

ACS Infect Dis. 2021 Dec 10;7(12):3303-3313. doi: 10.1021/acsinfecdis.1c00463. Epub 2021 Nov 9.

Abstract

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.

Keywords: Acinetobacter baumannii; Klebsiella pneumoniae; antibiotic adjuvant; colistin resistance.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Benzimidazoles / pharmacology
  • Colistin* / pharmacology
  • Microbial Sensitivity Tests
  • Salicylanilides*

Substances

  • Anti-Bacterial Agents
  • Benzimidazoles
  • Salicylanilides
  • Colistin