Design, synthesis, and biological evaluation of a novel series of quercetin diacylglucosides as potent anti-MRSA and anti-VRE agents

Hossion, Abugafar M. L.; Otsuka, Nao; Kandahary, Rafiya Khan; Tsuchiya, Tomofusa; Ogawa, Wakano; Iwado, Akimasa; Zamami, Yoshito; Sasaki, Kenji

doi:10.1016/j.bmcl.2010.02.060

Cited by 21 publications

(22 citation statements)

References 25 publications

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“…Verapamil did not show synergy within assay limits for these strains, due to low concentrations, as this EPI is of lower potency compared with compound 1 and reserpine. 25 In contrast to earlier findings that compound 1 has MIC values of 1-2 mg/L for a selection of clinically isolated MRSA strains, 11,12 we found that compound 1 had MIC values of 25 mg/L for the S. aureus strains used in our study. This might be explained by the use of different strains.…”

Section: Discussioncontrasting

confidence: 54%

“…9,10 Compound 1 and related isomers have previously been found to have anti-methicillin-resistant S. aureus (MRSA) activity. 11,12 The 2,3-coumaroyl isomer of compound 1 has been shown not to cause acute toxicity in mice at 20 mg/kg/day. 13 The NorA inhibitory activity of compound 1 reported in this publication has not been reported previously.…”

Section: Introductionmentioning

confidence: 99%

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Novel inhibitory activity of the Staphylococcus aureus NorA efflux pump by a kaempferol rhamnoside isolated from Persea lingue Nees

Holler

Christensen

Slotved

et al. 2012

Journal of Antimicrobial Chemotherapy

128

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Objectives: To isolate a plant-derived compound with efflux inhibitory activity towards the NorA transporter of Staphylococcus aureus.Methods: Bioassay-guided isolation was used, with inhibition of ethidium bromide efflux via NorA as a guide. Characterization of activity was carried out using MIC determination and potentiation studies of a fluoroquinolone antibiotic in combination with the isolated compound. Everted membrane vesicles of Escherichia coli cells enriched with NorA were prepared to study efflux inhibitory activity in an isolated manner.Results: The ethanolic extract of Persea lingue was subjected to bioassay-guided fractionation and led to the isolation of the known compound kaempferol-3-O-a-L-(2,4-bis-E-p-coumaroyl)rhamnoside (compound 1). Evaluation of the dose-response relationship of compound 1 showed that ethidium bromide efflux was inhibited, with an IC 50 value of 2 mM. The positive control, reserpine, was found to have an IC 50 value of 9 mM. Compound 1 also inhibited NorA in enriched everted membrane vesicles of E. coli. Potentiation studies revealed that compound 1 at 1.56 mg/L synergistically increased the antimicrobial activity of ciprofloxacin 8-fold against a NorA overexpresser, and the synergistic activity was exerted at a fourth of the concentration necessary for reserpine. Compound 1 was not found to exert a synergistic effect on ciprofloxacin against a norA deletion mutant. The 2,3-coumaroyl isomer of compound 1 has been shown previously not to cause acute toxicity in mice at 20 mg/kg/day. Conclusions:Our results show that compound 1 acts through inhibition of the NorA efflux pump. Combination of compound 1 with subinhibitory concentrations of ciprofloxacin renders a wild-type more susceptible and a NorA overexpresser S. aureus susceptible.

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Section: Discussioncontrasting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Novel inhibitory activity of the Staphylococcus aureus NorA efflux pump by a kaempferol rhamnoside isolated from Persea lingue Nees

Holler

Christensen

Slotved

et al. 2012

Journal of Antimicrobial Chemotherapy

128

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“…As seen in Table 1, compounds 2 and 3 showed null or moderate bacteriostatic activity, with no killing effect on either bacterium. Even though there are precedents in the literature about the antibacterial activity exerted by compound 2 against E. coli and against some methicillin-susceptible and methicillin-resistant S. aureus (Hirai et al 2010;Kuete et al 2011), other authors reported a lack of effectiveness (Hossion et al 2010;Li et al 2009) matching that obtained in this work. The level of activity shown by compound 3 against E. coli and S. aureus, does not match that found by Van Puyvelde et al (1989), but it does agree with the results obtained by Talib et al (2012) in a microtiter plate dilution test performed against E. coli.…”

Section: Determination Of Mics and Mbcscontrasting

confidence: 71%

Understanding the interactions between metabolites isolated from Achyrocline satureioides in relation to its antibacterial activity

2013

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“…Maybe the fluorine modulates the electronic effects on phenyl rings and also influences the steric characteristics and the hydrophilicÀhydrophobic balance of these molecules. 28 On the other hand, compounds having comparatively high MW and bulky side chains did not inhibit the growth of Gramnegative organisms, even at high concentrations, despite showing pronounced E. coli DNA gyrase supercoiling inhibition. The reason for these results is not clear, but hindrance of penetration into Gram-negative organism through the porin channel might be involved.…”

Section: Journal Of Medicinal Chemistrymentioning

confidence: 99%

Quercetin Diacylglycoside Analogues Showing Dual Inhibition of DNA Gyrase and Topoisomerase IV as Novel Antibacterial Agents

et al. 2011

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A structure-guided molecular design approach was used to optimize quercetin diacylglycoside analogues that inhibit bacterial DNA gyrase and topoisomerase IV and show potent antibacterial activity against a wide spectrum of relevant pathogens responsible for hospital- and community-acquired infections. In this paper, such novel 3,7-diacylquercetin, quercetin 6''-acylgalactoside, and quercetin 2'',6''-diacylgalactoside analogues of lead compound 1 were prepared to assess their target specificities and preferences in bacteria. The significant enzymatic inhibition of both Escherichia coli DNA gyrase and Staphylococcus aureus topoIV suggest that these compounds are dual inhibitors. Most of the investigated compounds exhibited pronounced inhibition with MIC values ranging from 0.13 to 128 μg/mL toward the growth of multidrug-resistant Gram-positive methicillin-resistant S. aureus, methicillin sensitive S. aureus, vancomycin-resistant enterococci (VRE), vancomycin intermediate S. aureus, and Streptococcus pneumoniae bacterial strains. Structure-activity relationship studies revealed that the acyl moiety was absolutely essential for activity against Gram-positive organisms. The most active compound 5i was 512-fold more potent than vancomycin and 16-32-fold more potent than 1 against VRE strains. It also has realistic in situ intestinal absorption in rats and showed very low acute toxicity in mice. So far, this compound can be regarded as a leading antibacterial agent.

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Design, synthesis, and biological evaluation of a novel series of quercetin diacylglucosides as potent anti-MRSA and anti-VRE agents

Cited by 21 publications

References 25 publications

Novel inhibitory activity of the Staphylococcus aureus NorA efflux pump by a kaempferol rhamnoside isolated from Persea lingue Nees

Novel inhibitory activity of the Staphylococcus aureus NorA efflux pump by a kaempferol rhamnoside isolated from Persea lingue Nees

Understanding the interactions between metabolites isolated from Achyrocline satureioides in relation to its antibacterial activity

Quercetin Diacylglycoside Analogues Showing Dual Inhibition of DNA Gyrase and Topoisomerase IV as Novel Antibacterial Agents

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