Discovery of 1,2-diaryl-3-oxopyrazolidin-4-carboxamides as a new class of MurA enzyme inhibitors and characterization of their antibacterial activity.
Antibacterial agents
Clostridioides difficile
Fosfomycin resistance
MurA enzyme
Peptidoglycan
Pyrazolidinone derivatives
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
05 Dec 2023
05 Dec 2023
Historique:
received:
13
04
2023
revised:
29
08
2023
accepted:
01
09
2023
medline:
3
11
2023
pubmed:
18
9
2023
entrez:
17
9
2023
Statut:
ppublish
Résumé
The cytoplasmic steps of peptidoglycan synthesis represent an important targeted pathway for development of new antibiotics. Herein, we report the synthesis of novel 3-oxopyrazolidin-4-carboxamide derivatives with variable amide side chains as potential antibacterial agents targeting MurA enzyme, the first committed enzyme in these cytosolic steps. Compounds 15 (isoindoline-1,3-dione-5-yl), 16 (4-(1H-pyrazol-4-yl)phenyl), 20 (5-cyanothiazol-2-yl), 21 and 31 (5-nitrothiazol-2-yl derivatives) exhibited the most potent MurA inhibition, with IC
Identifiants
pubmed: 37717380
pii: S0223-5234(23)00756-0
doi: 10.1016/j.ejmech.2023.115789
pii:
doi:
Substances chimiques
Fosfomycin
2N81MY12TE
UDP-N-acetylglucosamine 1-carboxyvinyltransferase
EC 2.5.1.7
Anti-Bacterial Agents
0
Alkyl and Aryl Transferases
EC 2.5.-
Enzyme Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
115789Informations de copyright
Copyright © 2023 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.