Discovery of a New Class of Non-β-lactam Inhibitors of Penicillin-Binding Proteins with Gram-Positive Antibacterial Activity

[Image: see text] Infections caused by hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA) are a serious global public-health concern, as MRSA has become broadly resistant to many classes of antibiotics. We disclose herein the discovery of a new class of non-β-lactam antibiotics, the ox...

Descripción completa

Detalles Bibliográficos
Autores principales: O’Daniel, Peter I., Peng, Zhihong, Pi, Hualiang, Testero, Sebastian A., Ding, Derong, Spink, Edward, Leemans, Erika, Boudreau, Marc A., Yamaguchi, Takao, Schroeder, Valerie A., Wolter, William R., Llarrull, Leticia I., Song, Wei, Lastochkin, Elena, Kumarasiri, Malika, Antunes, Nuno T., Espahbodi, Mana, Lichtenwalter, Katerina, Suckow, Mark A., Vakulenko, Sergei, Mobashery, Shahriar, Chang, Mayland
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985699/
https://www.ncbi.nlm.nih.gov/pubmed/24517363
http://dx.doi.org/10.1021/ja500053x
Descripción
Sumario:[Image: see text] Infections caused by hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA) are a serious global public-health concern, as MRSA has become broadly resistant to many classes of antibiotics. We disclose herein the discovery of a new class of non-β-lactam antibiotics, the oxadiazoles, which inhibit penicillin-binding protein 2a (PBP2a) of MRSA. The oxadiazoles show bactericidal activity against vancomycin- and linezolid-resistant MRSA and other Gram-positive bacterial strains, in vivo efficacy in a mouse model of infection, and have 100% oral bioavailability.

Ejemplares similares