info:eu-repo/semantics/article
Structure-Activity Relationship for the Oxadiazole Class of Antibiotics
Fecha
2015-02Registro en:
Spink, Edward; Ding, Derong; Peng, Zhihong; Boudreau, Marc A.; Leemans, Erika; et al.; Structure-Activity Relationship for the Oxadiazole Class of Antibiotics; American Chemical Society; Journal of Medicinal Chemistry; 58; 3; 2-2015; 1380-1389
0022-2623
Autor
Spink, Edward
Ding, Derong
Peng, Zhihong
Boudreau, Marc A.
Leemans, Erika
Lastochkin, Elena
Song, Wei
Lichtenwalter, Katerina
O’Daniel, Peter I.
Testero, Sebastian Andres
Pi, Hualiang
Schroeder, Valerie A.
Wolter, William R.
Antunes, Nuno T.
Suckow, Mark A.
Vakulenko, Sergei
Chang, Mayland
Mobashery, Shahriar
Resumen
The structure-activity relationship (SAR) for the newly discovered oxadiazole class of antibiotics is described with evaluation of 120 derivatives of the lead structure. This class of antibiotics was discovered by in silico docking and scoring against the crystal structure of a penicillin-binding protein. They impair cell-wall biosynthesis and exhibit activities against the Gram-positive bacterium Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant and linezolid-resistant S. aureus. 5-(1H-Indol-5-yl)-3-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,2,4-oxadiazole (antibiotic 75b) was efficacious in a mouse model of MRSA infection, exhibiting a long half-life, a high volume of distribution, and low clearance. This antibiotic is bactericidal and is orally bioavailable in mice. This class of antibiotics holds great promise in recourse against infections by MRSA.