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SAR Studies Leading to the Identification of a Novel Series of Metallo-?-lactamase Inhibitors for the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections That Display Efficacy in an Animal Infection Model.

ABSTRACT: The clinical effectiveness of carbapenem antibiotics such as meropenem is becoming increasingly compromised by the spread of both metallo-?-lactamase (MBL) and serine-?-lactamase (SBL) enzymes on mobile genetic elements, stimulating research to find new ?-lactamase inhibitors to be used in conjunction with carbapenems and other ?-lactam antibiotics. Herein, we describe our initial exploration of a novel chemical series of metallo-?-lactamase inhibitors, from concept to efficacy, in a survival model using an advanced tool compound (ANT431) in conjunction with meropenem.

SUBMITTER: Leiris S 

PROVIDER: S-EPMC6332448 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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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.

Leiris Simon S   Coelho Alicia A   Castandet Jérôme J   Bayet Maëlle M   Lozano Clarisse C   Bougnon Juliette J   Bousquet Justine J   Everett Martin M   Lemonnier Marc M   Sprynski Nicolas N   Zalacain Magdalena M   Pallin Thomas David TD   Cramp Michael C MC   Jennings Neil N   Raphy Gilles G   Jones Mark W MW   Pattipati Ramesh R   Shankar Battu B   Sivasubrahmanyam Relangi R   Soodhagani Ashok K AK   Juventhala Ramakrishna R RR   Pottabathini Narender N   Pothukanuri Srinivasu S   Benvenuti Manuela M   Pozzi Cecilia C   Mangani Stefano S   De Luca Filomena F   Cerboni Giulia G   Docquier Jean-Denis JD   Davies David T DT  

ACS infectious diseases 20181130 1

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 mo  ...[more]

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