Cinnamonitrile Adjuvants Restore Susceptibility to β-Lactams against Methicillin-Resistant Staphylococcus aureus
| Autor: | Shahriar Mobashery, Choon Kim, Yuanyuan Qian, Enrico Speri, Elena Lastochkin, Jed F. Fisher, Stefania De Benedetti, Jennifer Fishovitz |
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| Rok vydání: | 2019 |
| Předmět: |
010405 organic chemistry
Chemistry Organic Chemistry biochemical phenomena metabolism and nutrition medicine.disease_cause 01 natural sciences Biochemistry Methicillin-resistant Staphylococcus aureus 0104 chemical sciences Microbiology Penicillin 010404 medicinal & biomolecular chemistry Antibiotic resistance Drug Discovery β lactams polycyclic compounds medicine Staphylococcus aureus infections medicine.drug |
| Zdroj: | ACS Med Chem Lett |
| ISSN: | 1948-5875 |
| Popis: | [Image: see text] 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. |
| Databáze: | OpenAIRE |
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