Discovery of niclosamide and its O-alkylamino-tethered derivatives as potent antibacterial agents against carbapenemase-producing and/or colistin resistant Enterobacteriaceae isolates.
Bioorg Med Chem Lett
; 29(11): 1399-1402, 2019 06 01.
Article
in En
| MEDLINE
| ID: mdl-30954430
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Resistance, Bacterial
/
Enterobacteriaceae
/
Drug Discovery
/
Carbapenem-Resistant Enterobacteriaceae
/
Anti-Bacterial Agents
/
Niclosamide
Limits:
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2019
Document type:
Article
Affiliation country:
United States
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM