Abstract
Aim: Increasing antimicrobial resistance has compromised the effectiveness of many antibiotics, including those used to treat staphylococcal infections like methicillin-resistant Staphylococcus aureus. The development of combination therapies, where antimicrobial agents are used with compounds that inhibit resistance pathways is a promising strategy. Results/methodology: The Raf kinase inhibitor GW5074 exhibited selective in vitro activity against Gram-positive bacteria, including clinical isolates of S. aureus with a minimum inhibitory concentration (MIC) of 2-8 μg/ml. GW5074 was effective in vivo in the Galleria mellonella infection model. The compound showed synergy with gentamicin by lowering MIC by fourfold, compared with gentamicin MIC alone. Conclusion: This work demonstrates the antimicrobial properties of GW5074 and supports further investigation of the kinase inhibitors as antibiotic adjuvants.
Original language | English |
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Pages (from-to) | 1941-1952 |
Number of pages | 12 |
Journal | Future Medicinal Chemistry |
Volume | 8 |
Issue number | 16 |
DOIs | |
State | Published - Oct 2016 |
Bibliographical note
Publisher Copyright:© 2016 Future Science Ltd.
Keywords
- GW5074
- Staphylococcus aureus
- gentamicin