Chalcone inhibitors of the NorA efflux pump in Staphylococcus aureus whole cells and enriched everted membrane vesicles

Jes Gitz Holler; Hans Christian Slotved; Per Molgaard; Carl Erik Olsen; Soren Brogger Christensen

doi:10.1016/j.bmc.2012.05.025

Chalcone inhibitors of the NorA efflux pump in Staphylococcus aureus whole cells and enriched everted membrane vesicles

Jes Gitz Holler^*, Hans Christian Slotved, Per Molgaard, Carl Erik Olsen, Soren Brogger Christensen

^*Corresponding author

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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.

Originalsprog	Engelsk
Tidsskrift	Bioorganic and Medicinal Chemistry
Vol/bind	20
Udgave nummer	14
Sider (fra-til)	4514-4521
Antal sider	8
ISSN	0968-0896
DOI	https://doi.org/10.1016/j.bmc.2012.05.025
Status	Udgivet - 15 jul. 2012
Udgivet eksternt	Ja

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10.1016/j.bmc.2012.05.025

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title = "Chalcone inhibitors of the NorA efflux pump in Staphylococcus aureus whole cells and enriched everted membrane vesicles",

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.",

keywords = "Antibiotic resistance, Antibiotics, Chalcones, MRSA, Natural compounds, Staphylococcus aureus",

author = "Holler, {Jes Gitz} and Slotved, {Hans Christian} and Per Molgaard and Olsen, {Carl Erik} and Christensen, {Soren Brogger}",

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T1 - Chalcone inhibitors of the NorA efflux pump in Staphylococcus aureus whole cells and enriched everted membrane vesicles

AU - Holler, Jes Gitz

AU - Slotved, Hans Christian

AU - Molgaard, Per

AU - Olsen, Carl Erik

AU - Christensen, Soren Brogger

PY - 2012/7/15

Y1 - 2012/7/15

N2 - 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.

AB - 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.

KW - Antibiotic resistance

KW - Antibiotics

KW - Chalcones

KW - MRSA

KW - Natural compounds

KW - Staphylococcus aureus

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DO - 10.1016/j.bmc.2012.05.025

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JO - Bioorganic and Medicinal Chemistry

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