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Targeting Biofilm Associated Staphylococcus aureus Using Resazurin Based Drug-susceptibility Assay
Published on: May 5, 2016
3-Aryl-4-methyl-2-quinolones targeting multiresistant Staphylococcus aureus bacteria
Anne Doléans-Jordheim1, Jean-Baptiste Veron, Olivier Fendrich
1Université Claude Bernard Lyon 1, 69008 Lyon, France.
Chemmedchem
|February 26, 2013
Summary
New quinolinone compounds inhibit the NorA efflux pump in Staphylococcus aureus, restoring antibiotic effectiveness. One compound shows both efflux pump inhibition and antimicrobial activity, making it a promising candidate for further study.
Area of Science:
- Microbiology
- Medicinal Chemistry
- Pharmacology
Background:
- The NorA efflux pump in Staphylococcus aureus reduces intracellular antibiotic levels, contributing to fluoroquinolone resistance.
- Efflux pump inhibitors (EPIs) are crucial for overcoming multidrug resistance in bacteria.
Purpose of the Study:
- To identify novel compounds that inhibit the NorA efflux pump in Staphylococcus aureus.
- To evaluate the potential of these compounds to restore ciprofloxacin activity against resistant strains.
Main Methods:
- Synthesis and characterization of 3-aryl-4-methyl-2-quinolin-2-one derivatives.
- Assay of compounds for NorA efflux pump inhibitory activity.
- Evaluation of restored ciprofloxacin efficacy against resistant Staphylococcus aureus strains.
Main Results:
- 3-aryl-4-methyl-2-quinolin-2-ones were identified as effective NorA efflux pump inhibitors.
- Compound 6c (5-hydroxy-7-methoxy-4-methyl-3-phenylquinolin-2-one) demonstrated significant EPI activity.
- Compound 6c also exhibited intrinsic antimicrobial properties and restored ciprofloxacin's activity.
Conclusions:
- 3-aryl-4-methyl-2-quinolin-2-ones represent a promising class of compounds for combating Staphylococcus aureus infections.
- Compound 6c is a potential candidate for further development due to its dual EPI and antimicrobial effects and favorable safety profile.
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