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.
Simon LeirisAlicia CoelhoJérôme M CastandetMaëlle BayetClarisse LozanoJuliette BougnonJustine BousquetMartin J EverettMarc LemonnierNicolas SprynskiMagdalena ZalacainThomas David PallinMichael C CrampNeil JenningsGilles RaphyMark W JonesRamesh PattipatiBattu ShankarRelangi SivasubrahmanyamAshok K SoodhaganiRamakrishna R JuventhalaNarender PottabathiniSrinivasu PothukanuriManuela BenvenutiCecilia PozziStefano ManganiFilomena De LucaGiulia CerboniJean Denis DocquierDavid T DaviesPublished in: ACS infectious diseases (2018)
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.