Discovery of niclosamide and its O-alkylamino-tethered derivatives as potent antibacterial agents against carbapenemase-producing and/or colistin resistant Enterobacteriaceae isolates

Jimin Xu, María Eugenia Pachón-Ibáñez, Tania Cebrero-Cangueiro, Haiying Chen, Javier Sánchez-Céspedes, Jia Zhou

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Carbapenemase-producing Enterobacteriaceae (CPE) represents the most worrisome evolution of the antibiotic resistance crisis, which is almost resistant to most of available antibiotics. This situation is getting even worse particularly due to the recent emergence of colistin resistance. Herein, niclosamide, an FDA-approved traditional drug, and its novel O-alkylamino-tethered derivatives were discovered as new and potent antibacterial agents against carbapenemase-producing and/or colistin resistant Enterobacteriaceae isolates. Among these molecules, compound 10 (HJC0431) with 4-aminobutyl moiety showed the broad antibacterial activities, effective against 6 strains. In vitro checkerboard and time-kill course studies demonstrated the synergistic effects of the screened compounds with colistin against the corresponding strains with various degrees.

Original languageEnglish (US)
JournalBioorganic and Medicinal Chemistry Letters
DOIs
StatePublished - Jan 1 2019

Keywords

  • Antibacterial agents
  • Carbapenemase-producing Enterobacteriaceae
  • Colistin resistance
  • Niclosamide derivatives
  • Synergistic effects

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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