A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections

• Published in: Molecules (Basel, Switzerland) Switzerland), 2018-07, Vol.23 (7), p.1776
• Main Authors: Campanini-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
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Antibacterial materials; Antibiotic resistance; Antibiotics; Cell lines; Chemical Phenomena; Clinical isolates; Drug Resistance, Multiple, Bacterial - drug effects; Enterococcus faecium - drug effects; Humans; Infections; Infectious diseases; Medical treatment; Methicillin; methicillin-resistant Staphylococcus aureus; Microbial Sensitivity Tests; Minimum inhibitory concentration; Models, Molecular; Molecular Structure; Multidrug resistance; Multidrug resistant organisms; quinonic-antibiotics; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus infections; Strains (organisms); Structure-Activity Relationship; Thiophenol; Vancomycin; vancomycin-resistant Enterococcus faecium; X-Ray Diffraction
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules23071776

A 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 (MRSA) and vancomycin-resistant (VREF) clinical isolates. We found remarkable activity against VREF for compounds and , were the MIC were 2/4 µg/mL and 4/4 µg/mL, respectively, while for vancomycin the MIC 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 and have an interesting potential to be developed as new antibacterial drugs against infections caused by VREF.