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dc.contributor.authorGupta V.K.-
dc.contributor.authorGaur R.-
dc.contributor.authorSharma A.-
dc.contributor.authorAkther J.-
dc.contributor.authorSaini M.-
dc.contributor.authorBhakuni R.S.-
dc.contributor.authorPathania, R.-
dc.date.accessioned2020-09-30T11:33:37Z-
dc.date.available2020-09-30T11:33:37Z-
dc.date.issued2019-
dc.identifier.citationBioorganic Chemistry (2019), 83(): 214-225-
dc.identifier.issn452068-
dc.identifier.other30380450-
dc.identifier.urihttps://doi.org/10.1016/j.bioorg.2018.10.024-
dc.identifier.urihttp://repository.iitr.ac.in/handle/123456789/1248-
dc.description.abstractStaphylococcus aureus is the leading cause of bacteraemia and the dwindling supply of effective antibacterials has exacerbated the problem of managing infections caused by this bacterium. Isoliquiritigenin (ISL) is a plant flavonoid that displays therapeutic potential against S. aureus. The present study identified a novel mannich base derivatives of ISL, IMRG4, active against Vancomycin intermediate S. aureus (VISA). IMRG4 damages the bacterial membranes causing membrane depolarization and permeabilization, as determined by loss of salt tolerance, flow cytometric analysis, propidium idodie and fluorescent microscopy. It reduces the intracellular invasion of HEK-293 cells by S. aureus and decreases the staphylococcal load in different organs of infected mice models. In addition to anti-staphylococcal activity, IMRG4 inhibits the multidrug efflux pump, NorA, which was determined by molecular docking and EtBr efflux assays. In combination, IMRG4 significantly reduces the MIC of norfloxacin for clinical strains of S. aureus including VISA. Development of resistance against IMRG4 alone and in combination with norfloxacin was low and IMRG4 prolongs the post-antibiotic effect of norfloxacin. These virtues combined with the low toxicity of IMRG4, assessed by MTT assay and haemolysis, makes it an ideal candidate to enter drug development pipeline against S. aureus. © 2018 Elsevier Inc.-
dc.language.isoen_US-
dc.publisherAcademic Press Inc.-
dc.relation.ispartofBioorganic Chemistry-
dc.subjectAntibacterial-
dc.subjectEfflux pump inhibitor-
dc.subjectMembrane disruption-
dc.subjectNatural products-
dc.subjectProton motive force-
dc.titleA novel bi-functional chalcone inhibits multi-drug resistant Staphylococcus aureus and potentiates the activity of fluoroquinolones-
dc.typeArticle-
dc.scopusid57196262614-
dc.scopusid36604273700-
dc.scopusid57217481823-
dc.scopusid57204467404-
dc.scopusid57204465219-
dc.scopusid6701502246-
dc.scopusid7004308029-
dc.affiliationGupta, V.K., Molecular Bacteriology and Chemical Genetics Lab, Department of Biotechnology, Indian Institute of Technology Roorkee, District HaridwarUttarakhand 247667, India-
dc.affiliationGaur, R., Medicinal Chemistry Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India-
dc.affiliationSharma, A., Molecular Bacteriology and Chemical Genetics Lab, Department of Biotechnology, Indian Institute of Technology Roorkee, District HaridwarUttarakhand 247667, India-
dc.affiliationAkther, J., Molecular Bacteriology and Chemical Genetics Lab, Department of Biotechnology, Indian Institute of Technology Roorkee, District HaridwarUttarakhand 247667, India-
dc.affiliationSaini, M., Molecular Bacteriology and Chemical Genetics Lab, Department of Biotechnology, Indian Institute of Technology Roorkee, District HaridwarUttarakhand 247667, India-
dc.affiliationBhakuni, R.S., Medicinal Chemistry Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India-
dc.affiliationPathania, R., Molecular Bacteriology and Chemical Genetics Lab, Department of Biotechnology, Indian Institute of Technology Roorkee, District HaridwarUttarakhand 247667, India-
dc.description.fundingThis work was supported by DST SERB NPDF grant no. PDF/2016/000065 to V.K.G with R.P. as mentor. J.A. is financially supported by Indian Council of Medical Research, India .-
dc.description.correspondingauthorPathania, R.; Department of Biotechnology, Indian Institute of Technology RoorkeeIndia; email: rpathfbs@iitr.ac.in-
Appears in Collections:Journal Publications [BT]

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