Abstract
A library of 117 chalcones was screened for efflux pump inhibitory (EPI) activity against NorA mediated ethidium bromide efflux. Five of the chalcones (5-7, 9, and 10) were active and two chalcones (9 and 10) were equipotent to reserpine with IC(50)-values of 9.0 and 7.7 μM, respectively. Twenty chalcones were subsequently proved to be inhibitors of the NorA efflux pump in everted membrane vesicles. Compounds 5, 7, and 9 synergistically increased the effect of ciprofloxacin on Staphylococcus aureus. Our results suggest that chalcones might be developed into drugs for overcoming multidrug resistance based on efflux transporters of microorganisms.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology
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Bacterial Proteins / antagonists & inhibitors*
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Bacterial Proteins / metabolism
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Biological Transport / drug effects
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Chalcone / analogs & derivatives*
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Chalcone / chemical synthesis
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Chalcone / pharmacology
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Ciprofloxacin / pharmacology
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Drug Synergism
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Microbial Sensitivity Tests
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Multidrug Resistance-Associated Proteins / antagonists & inhibitors*
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Multidrug Resistance-Associated Proteins / metabolism
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Staphylococcus aureus / drug effects
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Staphylococcus aureus / metabolism*
Substances
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Anti-Bacterial Agents
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Bacterial Proteins
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Multidrug Resistance-Associated Proteins
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NorA protein, Staphylococcus
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Ciprofloxacin
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Chalcone