Cinnamonitrile Adjuvants Restore Susceptibility to β-Lactams against Methicillin-Resistant .

β-Lactams are used routinely to treat infections. However, the emergence of methicillin-resistant (MRSA) renders them clinically precarious. We describe a class of cinnamonitrile adjuvants that restore the activity of oxacillin (a penicillin member of the β-lactams) against MRSA. The lead adjuvants were tested against six important strains of MRSA, one vancomycin-intermediate (VISA) strain, and one linezolid-resistant strain. Five compounds out of 84 total compounds showed broad potentiation. At 8 μM ()-3-(5-(3,4-dichlorobenzyl)-2-(trifluoromethoxy)phenyl)-2-(methylsulfonyl)acrylonitrile () potentiated oxacillin with a >4000-fold reduction of its MIC (from 256 to 0.06 mg·L). This class of adjuvants holds promise for reversal of the resistance phenotype of MRSA.