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

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

Resultado de la investigación: Article

  • 1 Citas

Resumen

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.

IdiomaEnglish
PublicaciónMolecules (Basel, Switzerland)
Volumen23
Número de edición7
DOI
EstadoPublished - 19 jul 2018
Publicado de forma externa

Huella dactilar

Enterococcus faecium
antibiotics
infectious diseases
Vancomycin
Anti-Bacterial Agents
Infection
Cells
Microbial Sensitivity Tests
Structure-Activity Relationship
Methicillin-Resistant Staphylococcus aureus
Arsenals
Methicillin
Communicable Diseases
Cell Survival
broths
Bacteria
Cell Line
Screening
staphylococcus
rings

Keywords

    ASJC Scopus subject areas

    • Analytical Chemistry
    • Chemistry (miscellaneous)
    • Molecular Medicine
    • Pharmaceutical Science
    • Drug Discovery
    • Physical and Theoretical Chemistry
    • Organic Chemistry

    Citar esto

    Campanini-Salinas, J., Andrades-Lagos, J., Gonzalez Rocha, G., Choquesillo-Lazarte, D., Bollo Dragnic, S., Faúndez, M., ... Vásquez-Velásquez, D. (2018). A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections. Molecules (Basel, Switzerland), 23(7). https://doi.org/10.3390/molecules23071776
    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. / A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections. En: Molecules (Basel, Switzerland). 2018 ; Vol. 23, N.º 7.
    @article{9850ace182dd468cbd37b91c1f14282b,
    title = "A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections",
    abstract = "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{\circledR} strains using the broth microdilution method. The compounds exhibited minimum inhibitory concentrations (MIC) of 1⁻32 μg/mL against Gram-positive ATCC{\circledR} 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.",
    keywords = "antibacterial activity, methicillin-resistant Staphylococcus aureus, quinonic-antibiotics, vancomycin-resistant Enterococcus faecium",
    author = "Javier Campanini-Salinas and Juan Andrades-Lagos and {Gonzalez Rocha}, Gerardo and Duane Choquesillo-Lazarte and {Bollo Dragnic}, Soledad and Mario Fa{\'u}ndez and Pedro Alarc{\'o}n and Francisco Silva and Roberto Vidal and Edison Salas-Huenuleo and Marcelo Kogan and Jaime Mella and {Recabarren Gajardo}, Gonzalo and David V{\'a}squez-Vel{\'a}squez",
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    Campanini-Salinas, J, Andrades-Lagos, J, Gonzalez Rocha, G, Choquesillo-Lazarte, D, Bollo Dragnic, S, Faúndez, M, Alarcón, P, Silva, F, Vidal, R, Salas-Huenuleo, E, Kogan, M, Mella, J, Recabarren Gajardo, G & Vásquez-Velásquez, D 2018, 'A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections' Molecules (Basel, Switzerland), vol. 23, n.º 7. https://doi.org/10.3390/molecules23071776

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

    En: Molecules (Basel, Switzerland), Vol. 23, N.º 7, 19.07.2018.

    Resultado de la investigación: Article

    TY - JOUR

    T1 - A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections

    AU - Campanini-Salinas, Javier

    AU - Andrades-Lagos, Juan

    AU - Gonzalez Rocha, Gerardo

    AU - Choquesillo-Lazarte, Duane

    AU - Bollo Dragnic, Soledad

    AU - Faúndez, Mario

    AU - Alarcón, Pedro

    AU - Silva, Francisco

    AU - Vidal, Roberto

    AU - Salas-Huenuleo, Edison

    AU - Kogan, Marcelo

    AU - Mella, Jaime

    AU - Recabarren Gajardo, Gonzalo

    AU - Vásquez-Velásquez, David

    PY - 2018/7/19

    Y1 - 2018/7/19

    N2 - 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.

    AB - 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.

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    KW - methicillin-resistant Staphylococcus aureus

    KW - quinonic-antibiotics

    KW - vancomycin-resistant Enterococcus faecium

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    Campanini-Salinas J, Andrades-Lagos J, Gonzalez Rocha G, Choquesillo-Lazarte D, Bollo Dragnic S, Faúndez M y otros. A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections. Molecules (Basel, Switzerland). 2018 jul 19;23(7). https://doi.org/10.3390/molecules23071776