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Synergistic Effects Between Thioxanthones and Oxacillin Against Methicillin-Resistant Staphylococcus aureus
Lucinda J Bessa1,2, Andreia Palmeira3, Ana S Gomes3
11 Laboratório de Microbiologia e Tecnologia Alimentar, Departamento de Produção Aquática, Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto , Porto, Portugal .
Microbial Drug Resistance (Larchmont, N.Y.)
|March 20, 2015
Summary
Researchers screened (thio)xanthone derivatives for antibacterial activity. Two thioxanthone compounds showed synergy with oxacillin against methicillin-resistant Staphylococcus aureus (MRSA), potentially restoring antibiotic effectiveness.
Area of Science:
- Medicinal Chemistry
- Antimicrobial Resistance
- Drug Discovery
Background:
- Extensive antimicrobial use has led to widespread drug resistance, limiting treatment options for bacterial infections.
- There is a critical need for novel antimicrobials and compounds that can restore or enhance the efficacy of existing antibiotics.
Purpose of the Study:
- To screen a library of 40 (thio)xanthone derivatives for antibacterial activity.
- To evaluate the synergistic effects of these compounds when combined with conventional antibiotics against resistant bacteria.
Main Methods:
- Screening of 40 (thio)xanthone derivatives for antibacterial activity against Gram-positive bacteria.
- Testing synergistic effects in combination with antibiotics, particularly against methicillin-resistant Staphylococcus aureus (MRSA).
- Molecular docking simulations of active thioxanthone derivatives with penicillin-binding protein 2A (PBP2A).
Main Results:
- Nine (thio)xanthone derivatives exhibited antibacterial activity; four showed activity against MRSA.
- Thioxanthone 10 displayed antibacterial activity and synergy with ampicillin and oxacillin against MRSA.
- Thioxanthone 9, though not antibacterial, showed significant synergy with oxacillin against MRSA, with docking revealing binding to PBP2A.
Conclusions:
- Thioxanthone derivatives 9 and 10 demonstrate potential for restoring oxacillin's activity against MRSA.
- Binding to the allosteric domain of PBP2A may explain the observed synergistic effects of these thioxanthones.
- These compounds represent promising leads for developing strategies to combat MRSA infections.
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