Discovery of niclosamide and its O-alkylamino-tethered derivatives as potent antibacterial agents against carbapenemase-producing and/or colistin resistant Enterobacteriaceae isolates. Issue 11 (1st June 2019)

• Record Type: Journal Article
• Authors: Xu, Jimin; Pachón-Ibáñez, María Eugenia; Cebrero-Cangueiro, Tania; Chen, Haiying; Sánchez-Céspedes, Javier; Zhou, Jia
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 11(2019)
• Page Start: 1399
• Page End: 1402
• Publication Date: 2019-06-01
• Subjects: Niclosamide derivatives -- Antibacterial agents -- Carbapenemase-producing Enterobacteriaceae -- Colistin resistance -- Synergistic effects; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.03.032
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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, compound10 (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.