Abstract
Aim: Compound 1-(4-chlorophenyl)-4,4,4-trifluoro-3-hydroxy-2-buten-1-one (compound 1) was identified as a hit against methicillin-resistant Staphylococcus aureus (MRSA) strain MW2. Methods & results: The MIC of compound 1 against MRSA was 4 μg/ml. The compound showed enhanced activity at acidic pH by lowering bacterial intracellular pH and exhibited no lysis of human red blood cells at up to 64 μg/ml and its IC50 against HepG2 cells was 32 μg/ml. The compound reduced 1-log10 colony forming units of intracellular MRSA in macrophages and prolonged the survival of MRSA-infected Caenorhabditis elegans (p = 0.0015) and Galleria mellonella (p = 0.0002). Conclusion: Compound 1 is a protonophore with potent in vitro and in vivo activity against MRSA and no toxicity in mammalian cells up to 8 μg/ml that warrants further investigation as a novel antibacterial.
Original language | English (US) |
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Pages (from-to) | 1401-1411 |
Number of pages | 11 |
Journal | Future Medicinal Chemistry |
Volume | 9 |
Issue number | 12 |
DOIs | |
State | Published - Aug 2017 |
Keywords
- antibiotic
- Galleria mellonella
- macrophages
- MRSA infection
- protonophore
- S. aureus
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology
- Drug Discovery