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

Autor:	Mayland Chang, Leticia I. Llarrull, Elena Lastochkin, Sebastián A. Testero, Derong Ding, Valerie A. Schroeder, Mark A. Suckow, Shahriar Mobashery, Nuno T. Antunes, Zhihong Peng, Malika Kumarasiri, Erika Leemans, Katerina Lichtenwalter, Wei Song, Mana Espahbodi, Peter I. O’Daniel, Hualiang Pi, William R. Wolter, Edward Spink, Sergei B. Vakulenko, Marc A. Boudreau, Takao Yamaguchi
Přispěvatelé:	O'Daniel, Peter I, Peng, Zhihong, Pi, Hualiang, Testero, Sebastian A, Kumarasiri, Malika, Chang, Mayland
Rok vydání:	2014
Předmět:	Methicillin-Resistant Staphylococcus aureus Models Molecular Penicillin binding proteins Protein Conformation medicine.drug_class Gram-positive bacteria Antibiotics Biological Availability Microbial Sensitivity Tests Pharmacology Gram-Positive Bacteria beta-Lactams medicine.disease_cause Biochemistry Article Catalysis Microbiology Mice Colloid and Surface Chemistry Cell Wall In vivo Drug Discovery medicine Animals Penicillin-Binding Proteins Computer Simulation non-β-lactam inhibitors Oxadiazoles biology Chemistry General Chemistry biochemical phenomena metabolism and nutrition bacterial infections and mycoses biology.organism_classification Methicillin-resistant Staphylococcus aureus Anti-Bacterial Agents antibacterial penicillin Staphylococcus aureus Vancomycin Antibacterial activity medicine.drug
Zdroj:	Journal of the American Chemical Society
ISSN:	1520-5126 0002-7863
DOI:	10.1021/ja500053x
Popis:	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.
Databáze:	OpenAIRE
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