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Coumarin derivatives as promising xanthine oxidase inhibitors

dc.contributor.authorFais A.
dc.contributor.authorEra B.
dc.contributor.authorAsthana S.
dc.contributor.authorSogos V.
dc.contributor.authorMedda R.
dc.contributor.authorSantana L.
dc.contributor.authorUriarte E.
dc.contributor.authorMatos M.J.
dc.contributor.authorDelogu F.
dc.contributor.authorKumar A.
dc.date.accessioned2020-09-02T22:17:22Z
dc.date.available2020-09-02T22:17:22Z
dc.date.issued2018
dc.identifier10.1016/j.ijbiomac.2018.09.001
dc.identifier.citation120, , 1286-1293
dc.identifier.issn01418130
dc.identifier.urihttps://hdl.handle.net/20.500.12728/4414
dc.descriptionXanthine oxidase (XO) is an interesting target for the synergic treatment of several diseases. Coumarin scaffold plays an important role in the design of efficient and potent inhibitors. In the current work, twenty 3-arylcoumarins and eight 3-heteroarylcoumarins were evaluated for their ability to inhibit XO. Among all the candidates, 5,7-dihydroxy-3-(3′-hydroxyphenyl)coumarin (compound 20) proved to be the best inhibitor with an IC50 of 2.13 μM, being 7-fold better than the reference compound, allopurinol (IC50 = 14.75 μM). To deeply understand the potential of this compound, the inhibition mode was also evaluated. Compound 20 showed an uncompetitive profile of inhibition. Molecular docking studies were carried out to analyze the interaction of compound 20 with the studied enzyme. The binding mode involving residues different from the catalytic site of the binding pocket, is compatible to the observed uncompetitive inhibition. Compound 20 was not cytotoxic at its IC50 value, as demonstrated by the viability of 99.1% in 3 T3 cells. Furthermore, pharmacokinetics and physicochemical properties were also calculated, which corroborated with the potential of the studied compounds as promising XO inhibitors. © 2018
dc.language.isoen
dc.publisherElsevier B.V.
dc.subjectCoumarin derivatives
dc.subjectMolecular docking
dc.subjectXanthine oxidase inhibition
dc.subject3 heteroarylcoumarin derivative
dc.subject5,7 dihydroxy 3 (3' hydroxyphenyl)coumarin
dc.subjectallopurinol
dc.subjectarylcoumarin derivative
dc.subjectcoumarin derivative
dc.subjectmolecular scaffold
dc.subjectunclassified drug
dc.subjectxanthine oxidase
dc.subjectxanthine oxidase inhibitor
dc.subjectallopurinol
dc.subjectcoumarin
dc.subjectcoumarin derivative
dc.subjectenzyme inhibitor
dc.subject3T3 cell line
dc.subjectamino acid sequence
dc.subjectanimal cell
dc.subjectArticle
dc.subjectbinding site
dc.subjectcontrolled study
dc.subjectdrug safety
dc.subjectenzyme active site
dc.subjectenzyme binding
dc.subjectenzyme inhibition
dc.subjectIC50
dc.subjectmolecular docking
dc.subjectmouse
dc.subjectnonhuman
dc.subjectpharmacokinetics
dc.subjectphysical chemistry
dc.subjectantagonists and inhibitors
dc.subjectchemical structure
dc.subjectchemistry
dc.subjectstructure activity relation
dc.subjectAllopurinol
dc.subjectCatalytic Domain
dc.subjectCoumarins
dc.subjectEnzyme Inhibitors
dc.subjectMolecular Docking Simulation
dc.subjectMolecular Structure
dc.subjectStructure-Activity Relationship
dc.subjectXanthine Oxidase
dc.titleCoumarin derivatives as promising xanthine oxidase inhibitors
dc.typeArticle


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