Cinnamonitrile Adjuvants Restore Susceptibility to ß-Lactams against Methicillin-Resistant Staphylococcus aureus.
ACS Med Chem Lett
; 10(8): 1148-1153, 2019 Aug 08.
Article
em En
| MEDLINE
| ID: mdl-31413798
ABSTRACT
ß-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 ß-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article