Back to Search
Start Over
A γ-Lactam Siderophore Antibiotic Effective against Multidrug-Resistant Gram-Negative Bacilli.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 2020 Jun 11; Vol. 63 (11), pp. 5990-6002. Date of Electronic Publication: 2020 Jun 02. - Publication Year :
- 2020
-
Abstract
- Treatment of multidrug-resistant Gram-negative bacterial pathogens represents a critical clinical need. Here, we report a novel γ-lactam pyrazolidinone that targets penicillin-binding proteins (PBPs) and incorporates a siderophore moiety to facilitate uptake into the periplasm. The MIC values of γ-lactam YU253434, 1 , are reported along with the finding that 1 is resistant to hydrolysis by all four classes of β-lactamases. The druglike characteristics and mouse PK data are described along with the X-ray crystal structure of 1 binding to its target PBP3.
- Subjects :
- Animals
Anti-Bacterial Agents chemical synthesis
Anti-Bacterial Agents metabolism
Anti-Bacterial Agents pharmacokinetics
Bacterial Proteins antagonists & inhibitors
Bacterial Proteins metabolism
Binding Sites
Catalytic Domain
Crystallography, X-Ray
Gram-Negative Bacteria drug effects
Half-Life
Lactams metabolism
Lactams pharmacokinetics
Lactams pharmacology
Mice
Microbial Sensitivity Tests
Molecular Docking Simulation
Penicillin-Binding Proteins antagonists & inhibitors
Penicillin-Binding Proteins metabolism
Pseudomonas aeruginosa metabolism
Siderophores metabolism
Anti-Bacterial Agents pharmacology
Drug Resistance, Multiple, Bacterial drug effects
Lactams chemistry
Siderophores chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4804
- Volume :
- 63
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 32420736
- Full Text :
- https://doi.org/10.1021/acs.jmedchem.0c00255