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A new kind of quinonic-antibiotic useful against multidrug-resistant S. aureus and E. faecium Infections

AuthorsCampanini-Salinas, Javier; Andrades-Lagos, Juan; Gonzalez Rocha, Gerardo; Choquesillo-Lazarte, Duane ; Bollo Dragnic, Soledad; Faúndez, Mario; Alarcón, Pedro; Silva, Francisco; Vidal, Roberto; Salas-Huenuleo, Edison; Kogan, Marcelo; Mella, Jaime; Recabarren Gajardo, Gonzalo; Vásquez-Velásquez, David
Methicillin-resistant staphylococcus aureus
Vancomycin-resistant enterococcus faecium
Antibacterial activity
Issue Date19-Jul-2018
PublisherMultidisciplinary Digital Publishing Institute
CitationMolecules 23(7): 1776 (2018)
AbstractA rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics and reducing the therapeutic arsenal available for treatment of infectious diseases. In the present study, we developed a new class of compounds with antibacterial activity obtained by a simple, two step synthesis and screened the products for in vitro antibacterial activity against ATCC® strains using the broth microdilution method. The compounds exhibited minimum inhibitory concentrations (MIC) of 1–32 μg/mL against Gram-positive ATCC® strains. The structure–activity relationship indicated that the thiophenol ring is essential for antibacterial activity and the substituents on the thiophenol ring module, for antibacterial activity. The most promising compounds detected by screening were tested against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) clinical isolates. We found remarkable activity against VREF for compounds 7 and 16, were the MIC50/90 were 2/4 µg/mL and 4/4 µg/mL, respectively, while for vancomycin the MIC50/90 was 256/512 µg/mL. Neither compound affected cell viability in any of the mammalian cell lines at any of the concentrations tested. These in vitro data show that compounds 7 and 16 have an interesting potential to be developed as new antibacterial drugs against infections caused by VREF.
Publisher version (URL)https://doi.org/10.3390/molecules23071776
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