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1. 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.

Author

Leiris S, Coelho A, Castandet J, Bayet M, Lozano C, Bougnon J, Bousquet J, Everett M, Lemonnier M, Sprynski N, Zalacain M, Pallin TD, Cramp MC, Jennings N, Raphy G, Jones MW, Pattipati R, Shankar B, Sivasubrahmanyam R, Soodhagani AK, Juventhala RR, Pottabathini N, Pothukanuri S, Benvenuti M, Pozzi C, Mangani S, De Luca F, Cerboni G, Docquier JD, and Davies DT

Subjects
Carbapenems pharmacology, Crystallography, X-Ray, Inhibitory Concentration 50, Meropenem pharmacology, Microbial Sensitivity Tests, Picolinic Acids chemistry, Picolinic Acids pharmacology, Protein Binding, Structure-Activity Relationship, beta-Lactamase Inhibitors pharmacology, beta-Lactamases, Anti-Bacterial Agents pharmacology, Carbapenem-Resistant Enterobacteriaceae drug effects, Drug Resistance, Multiple, Bacterial, Enterobacteriaceae Infections drug therapy, beta-Lactamase Inhibitors chemistry
Abstract

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.

Published
2019
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