IQUIR   05412
INSTITUTO DE QUIMICA ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Structure-activity relationship for the oxadiazole class of antiobiotics
Autor/es:
EDWARD SPINK; DERONG DING; ZHIHONG PENG; MARC A. BOUDREAU; ERIKA J. LEEMANS; ELENA LASHTOCHKIN; WEI SONG; KATERINA LICHTENWALTER; PETER I. O'DANIEL; SEBASTIAN A. TESTERO; HUALIANG PI; VALERIE A. SCHROEDER; WILLIAM R. WOLTER; NUNO T. ANTUNES; MARK A. SUCKOW; SERGEI VAKULENKO; MAYLAND CHANG; SHAHRIAR MOBASHERY
Lugar:
Islas Canarias
Reunión:
Workshop; 12th Beta-Lactamase Meeting.; 2014
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.