Exploration of the Structure-Activity Relationship of 1,2,4-Oxadiazole Antibiotics

We have recently disclosed the discovery of the class of 1,2,4-oxadiazole antibiotics, which emerged from in silico docking and scoring efforts. This class of antibacterials exhibits Gram-positive activity, particularly against Staphylococcus aureus. We define the structure–activity relationship (SAR) of this class of antibiotics with the synthesis and evaluation of a series of 59 derivatives with variations in the C ring or C and D rings. A total of 17 compounds showed activity against S. aureus. Four derivatives were evaluated against a panel of 16 Gram-positive strains, inclusive of several methicillin-resistant S. aureus strains. These compounds are broadly active against Gram-positive bacteria.Fil: Ding, Derong. University Of Notre Dame-indiana; Estados UnidosFil: Boudreau, Marc A.. University Of Notre Dame-indiana; Estados UnidosFil: Leemans, Erika J.. University Of Notre Dame-indiana; Estados UnidosFil: Spink, Edward. University Of Notre Dame-indiana; Estados UnidosFil: Yamaguchi, Takao. University Of Notre Dame-indiana; Estados UnidosFil: Testero, Sebastian Andres. University Of Notre Dame-indiana; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Química Rosario; ArgentinaFil: O'Daniel, Peter I.. University Of Notre Dame-indiana; Estados UnidosFil: Lastochkin, Elena. University Of Notre Dame-indiana; Estados UnidosFil: Chang, Mayland. University Of Notre Dame-indiana; Estados UnidosFil: Mobashery, Shahriar. University Of Notre Dame-indiana; Estados Unido