Optimization of 1,2,4-Triazole-3-thiones toward Broad-Spectrum Metallo-β-lactamase Inhibitors Showing Potent Synergistic Activity on VIM- and NDM-1-Producing Clinical Isolates.
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
22 12 2022
22 12 2022
Historique:
pubmed:
1
12
2022
medline:
24
12
2022
entrez:
30
11
2022
Statut:
ppublish
Résumé
Metallo-β-lactamases (MBLs) contribute to the resistance of Gram-negative bacteria to carbapenems, last-resort antibiotics at hospital, and MBL inhibitors are urgently needed to preserve these important antibacterial drugs. Here, we describe a series of 1,2,4-triazole-3-thione-based inhibitors displaying an α-amino acid substituent, which amine was mono- or disubstituted by (hetero)aryl groups. Compounds disubstituted by certain nitrogen-containing heterocycles showed submicromolar activities against VIM-type enzymes and strong NDM-1 inhibition (
Identifiants
pubmed: 36450011
doi: 10.1021/acs.jmedchem.2c01257
doi:
Substances chimiques
beta-Lactamase Inhibitors
0
beta-lactamase NDM-1
EC 3.5.2.6
Thiones
0
1,2,4-triazole
288-88-0
Anti-Bacterial Agents
0
beta-Lactamases
EC 3.5.2.6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM