Open AccessCinnamonitrile Adjuvants Restore Susceptibility to β-Lactams against Methicillin-Resistant Staphylococcus aureus
Author(s) -
Enrico Speri,
Choon Kim,
Stefania De Benedetti,
Yuanyuan Qian,
Elena Lastochkin,
Jennifer Fishovitz,
Jed F. Fisher,
Shahriar Mobashery
Publication year - 2019
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.9b00169
Subject(s) - staphylococcus aureus , microbiology and biotechnology , methicillin resistant staphylococcus aureus , medicine , beta lactam , staphylococcal infections , biology , antibiotics , bacteria , genetics
β-Lactams are used routinely to treat Staphylococcus aureus infections. However, the emergence of methicillin-resistant S. aureus (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 S. aureus (VISA) strain, and one linezolid-resistant S. aureus strain. Five compounds out of 84 total compounds showed broad potentiation. At 8 μM ( E )-3-(5-(3,4-dichlorobenzyl)-2-(trifluoromethoxy)phenyl)-2-(methylsulfonyl)acrylonitrile ( 26 ) potentiated oxacillin with a >4000-fold reduction of its MIC (from 256 to 0.06 mg·L -1 ). This class of adjuvants holds promise for reversal of the resistance phenotype of MRSA.