A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections
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, t...
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MDPI AG
2018-07-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/23/7/1776 |
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| author | Javier Campanini-Salinas Juan Andrades-Lagos Gerardo Gonzalez Rocha Duane Choquesillo-Lazarte Soledad Bollo Dragnic Mario Faúndez Pedro Alarcón Francisco Silva Roberto Vidal Edison Salas-Huenuleo Marcelo Kogan Jaime Mella Gonzalo Recabarren Gajardo David Vásquez-Velásquez |
| author_facet | Javier Campanini-Salinas Juan Andrades-Lagos Gerardo Gonzalez Rocha Duane Choquesillo-Lazarte Soledad Bollo Dragnic Mario Faúndez Pedro Alarcón Francisco Silva Roberto Vidal Edison Salas-Huenuleo Marcelo Kogan Jaime Mella Gonzalo Recabarren Gajardo David Vásquez-Velásquez |
| author_sort | Javier Campanini-Salinas |
| collection | DOAJ |
| description | 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 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. |
| first_indexed | 2024-04-13T19:41:56Z |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T19:41:56Z |
| publishDate | 2018-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-3d5bceafb92645069859d5a144ab502c2022-12-22T02:32:50ZengMDPI AGMolecules1420-30492018-07-01237177610.3390/molecules23071776molecules23071776A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium InfectionsJavier Campanini-Salinas0Juan Andrades-Lagos1Gerardo Gonzalez Rocha2Duane Choquesillo-Lazarte3Soledad Bollo Dragnic4Mario Faúndez5Pedro Alarcón6Francisco Silva7Roberto Vidal8Edison Salas-Huenuleo9Marcelo Kogan10Jaime Mella11Gonzalo Recabarren Gajardo12David Vásquez-Velásquez13Drug Development Laboratory, Faculty of Chemical and Pharmaceutical, Sciences, Universidad de Chile, Sergio Livingstone 1007, Santiago 8380492, ChileDrug Development Laboratory, Faculty of Chemical and Pharmaceutical, Sciences, Universidad de Chile, Sergio Livingstone 1007, Santiago 8380492, ChileLaboratorio de Investigación en Agentes Antibacterianos (LIAA), Departamento de Microbiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción 4070386, ChileLaboratorio de Estudios Cristalográficos, IACT (CSIC-UGR), Av. de las Palmeras 4, 18100 Armilla (Granada), SpainBioelectrochemistry Laboratory, Faculty of Chemical and Pharmaceutical, Sciences, Universidad de Chile, Santiago 8380492, ChileMolecular Pharmacology and Toxicology Laboratory, Pharmacy Department, Faculty of Chemistry, Pontificia Universidad Católica de Chile; Santiago 7820436, ChileAgents of bacterial meningitis laboratory, Instituto de Salud Pública de Chile, Santiago 7780050, ChileMicrobiology Unit, Clinical Laboratory, Clinical Hospital University of Chile; Santiago 8380456, ChileAntibiotics Laboratory, Microbiology Program, Biomedical Sciences Institute, Faculty of Medicine, Universidad de Chile, Santiago 8380453, ChileNanobiotechnology and Nanotoxicology Laboratory, Faculty of Chemical and Pharmaceutical Sciences, Universidad de Chile, Santiago 8380494, ChileNanobiotechnology and Nanotoxicology Laboratory, Faculty of Chemical and Pharmaceutical Sciences, Universidad de Chile, Santiago 8380494, ChileInstitute of Chemistry and Biochemistry, Faculty of Sciences, Universidad de Valparaíso, Playa Ancha, Valparaíso 2360102, ChileLaboratory of Synthesis of Bioactive Heterocycles, Pharmacy Department, Faculty of Chemistry, Pontificia Universidad Católica de Chile; Santiago 7820436, ChileDrug Development Laboratory, Faculty of Chemical and Pharmaceutical, Sciences, Universidad de Chile, Sergio Livingstone 1007, Santiago 8380492, ChileA 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.http://www.mdpi.com/1420-3049/23/7/1776quinonic-antibioticsmethicillin-resistant Staphylococcus aureusvancomycin-resistant Enterococcus faeciumantibacterial activity |
| spellingShingle | Javier Campanini-Salinas Juan Andrades-Lagos Gerardo Gonzalez Rocha Duane Choquesillo-Lazarte Soledad Bollo Dragnic Mario Faúndez Pedro Alarcón Francisco Silva Roberto Vidal Edison Salas-Huenuleo Marcelo Kogan Jaime Mella Gonzalo Recabarren Gajardo David Vásquez-Velásquez A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections Molecules quinonic-antibiotics methicillin-resistant Staphylococcus aureus vancomycin-resistant Enterococcus faecium antibacterial activity |
| title | A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections |
| title_full | A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections |
| title_fullStr | A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections |
| title_full_unstemmed | A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections |
| title_short | A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections |
| title_sort | new kind of quinonic antibiotic useful against multidrug resistant s aureus and e faecium infections |
| topic | quinonic-antibiotics methicillin-resistant Staphylococcus aureus vancomycin-resistant Enterococcus faecium antibacterial activity |
| url | http://www.mdpi.com/1420-3049/23/7/1776 |
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