The assemblage of covalent and metal binding dual functional scaffold for cross-class metallo-ß-lactamases inhibition.
Future Med Chem
; 11(18): 2381-2394, 2019 09.
Article
in En
| MEDLINE
| ID: mdl-31544522
ABSTRACT
Aim:
The discovery and development of novel broad-spectrum MßLs inhibitors are urgent to overcome antibiotic resistance mediated by MßLs. Methods &results:
Herein, the synthesized 21 compounds exhibited potent inhibition to the clinically important MßLs (NDM-1, IMP-1 and ImiS) and effectively restored the antibacterial efficacy of cefazolin and imipenem against Escherichia coli harboring MßLs. 5b was first identified to be dual functional broad-spectrum MßLs inhibitor through assemblage of covalent and metal binding scaffold, which irreversibly inhibited B1, B2 MßLs via forming a Se-S covalent bond, and competitively inhibited B3 MßLs by coordinating the metals at active site.Conclusion:
The designed compounds can serve as potent broad-spectrum MßLs inhibitors and combat MßLs-producing 'superbug' in combination with ß-lactams.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Beta-Lactamases
/
Escherichia coli
/
Beta-Lactamase Inhibitors
/
Anti-Bacterial Agents
Limits:
Animals
Language:
En
Journal:
Future Med Chem
Year:
2019
Document type:
Article