SAR Studies Leading to the Identification of a Novel Series of Metallo-β-lactamase Inhibitors for the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections That Display Efficacy in an Animal Infection Model.
Anti-Bacterial Agents
/ pharmacology
Carbapenem-Resistant Enterobacteriaceae
/ drug effects
Carbapenems
/ pharmacology
Crystallography, X-Ray
Drug Resistance, Multiple, Bacterial
Enterobacteriaceae Infections
/ drug therapy
Inhibitory Concentration 50
Meropenem
/ pharmacology
Microbial Sensitivity Tests
Picolinic Acids
/ chemistry
Protein Binding
Structure-Activity Relationship
beta-Lactamase Inhibitors
/ chemistry
beta-Lactamases
NDM-1
VIM-2
antibiotic resistance
efficacy
meropenem
metallo-β-lactamase inhibitor
Journal
ACS infectious diseases
ISSN: 2373-8227
Titre abrégé: ACS Infect Dis
Pays: United States
ID NLM: 101654580
Informations de publication
Date de publication:
11 01 2019
11 01 2019
Historique:
pubmed:
15
11
2018
medline:
15
1
2020
entrez:
15
11
2018
Statut:
ppublish
Résumé
The clinical effectiveness of carbapenem antibiotics such as meropenem is becoming increasingly compromised by the spread of both metallo-β-lactamase (MBL) and serine-β-lactamase (SBL) enzymes on mobile genetic elements, stimulating research to find new β-lactamase inhibitors to be used in conjunction with carbapenems and other β-lactam antibiotics. Herein, we describe our initial exploration of a novel chemical series of metallo-β-lactamase inhibitors, from concept to efficacy, in a survival model using an advanced tool compound (ANT431) in conjunction with meropenem.
Identifiants
pubmed: 30427656
doi: 10.1021/acsinfecdis.8b00246
pmc: PMC6332448
doi:
Substances chimiques
Anti-Bacterial Agents
0
Carbapenems
0
Picolinic Acids
0
beta-Lactamase Inhibitors
0
beta-Lactamases
EC 3.5.2.6
Meropenem
FV9J3JU8B1
picolinic acid
QZV2W997JQ
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
131-140Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 099212/Z/12
Pays : United Kingdom
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