Discovery of a New Class of Non-尾-lactam Inhibitors of Penicillin-Binding Proteins with Gram-Positive Antibacterial Activity
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- 作者：Peter I. O鈥橠aniel ; Zhihong Peng ; Hualiang Pi ; Sebastian A. Testero ; Derong Ding ; Edward Spink ; Erika Leemans ; Marc A. Boudreau ; Takao Yamaguchi ; Valerie A. Schroeder ; William R. Wolter ; Leticia I. Llarrull ; Wei Song ; Elena Lastochkin ; Malika Kumarasiri ; Nuno T. Antunes ; Mana Espahbodi ; Katerina Lichtenwalter ; Mark A. Suckow ; Sergei Vakulenko ; Shahriar Mobashery ; Mayland Chang
- 刊名：Journal of the American Chemical Society
- 出版年：2014
- 出版时间：March 5, 2014
- 年：2014
- 卷：136
- 期：9
- 页码：3664-3672
- 全文大小：391K
- 年卷期：v.136,no.9(March 5, 2014)
- ISSN：1520-5126
文摘
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-尾-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.