Chalcone inhibitors of the NorA efflux pump in Staphylococcus aureus whole cells and enriched everted membrane vesicles.
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.
University of Copenhagen, Faculty of Pharmaceutical Sciences, Department of Medicinal Chemistry, Denmark. jgh@farma.ku.dk
Jes Gitz
JG
Holler
Hans-Christian
HC
Slotved
Per
P
Mølgaard
Carl Erik
CE
Olsen
Søren Brøgger
SB
Christensen
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology; D004357:Drug Synergism; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002599:Chalcone; D002939:Ciprofloxacin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C075040:NorA protein, Staphylococcus