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 for this work

Research output: Contribution to journal › Journal article › Research › 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.

Original language	English
Journal	Bioorganic and Medicinal Chemistry
Volume	20
Issue number	14
Pages (from-to)	4514-4521
Number of pages	8
ISSN	0968-0896
DOIs	https://doi.org/10.1016/j.bmc.2012.05.025
Publication status	Published - 15 Jul 2012
Externally published	Yes

Keywords

Antibiotic resistance
Antibiotics
Chalcones
MRSA
Natural compounds
Staphylococcus aureus

Link to document

10.1016/j.bmc.2012.05.025

Cite this

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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}",

year = "2012",

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doi = "10.1016/j.bmc.2012.05.025",

language = "English",

volume = "20",

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journal = "Bioorganic and Medicinal Chemistry",

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TY - JOUR

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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U2 - 10.1016/j.bmc.2012.05.025

DO - 10.1016/j.bmc.2012.05.025

M3 - Journal article

C2 - 22682300

AN - SCOPUS:84863220948

SN - 0968-0896

VL - 20

SP - 4514

EP - 4521

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 14

ER -

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

Abstract

Keywords

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