2. Academic Validation
  3. Benzimidazole Isosteres of Salicylanilides Are Highly Active Colistin Adjuvants

Benzimidazole Isosteres of Salicylanilides Are Highly Active Colistin Adjuvants

  • ACS Infect Dis. 2021 Dec 10;7(12):3303-3313. doi: 10.1021/acsinfecdis.1c00463.
Haoting Li 1,  Anne E Mattingly 1,  Leigh A Jania 2,  Richard Smith 3,  Roberta J Melander 1,  Robert K Ernst 3,  Beverley H Koller 2,  Christian Melander 1
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
  • 2 Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
  • 3 Department of Microbial Pathogenesis, University of Maryland-Baltimore, Baltimore, Maryland 21201, United States.
PMID: 34752055 DOI: 10.1021/acsinfecdis.1c00463
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.

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