Characterization and screening of tight binding inhibitors of xanthine oxidase : an on-flow assay.

Simple item page
dc.contributor.authorRodrigues, Marili Villa Nova
dc.contributor.authorCorrea, Rodrigo de Souza
dc.contributor.authorVanzolini, Kenia Lourenço
dc.contributor.authorSantos, Diogenes Santiago
dc.contributor.authorBatista, Alzir Azevedo
dc.contributor.authorCass, Quezia Bezerra
dc.date.accessioned2017-08-09T18:56:20Z
dc.date.available2017-08-09T18:56:20Z
dc.date.issued2015
dc.description.abstractXanthine oxidase (XO) is an enzyme in the purine salvage pathway that catalyzes the oxidation of hypoxanthine to xanthine with subsequent production of uric acid from the xanthine oxidation, and it has been considered an important target of newly developed inhibitors. Based on the advantages of using immobilized capillary enzyme reactors (ICERs) in a 2D LC system as a tool for screening new enzymatic ligands, this work validated an XO-ICER using allopurinol as a positive control. Despite the complex interaction between XO and allopurinol due its tight binding nature, it was possible to recognize the inhibitory kinetics parameters through Morrison's equation. The tight binding nature of inhibition was established by varying the IC50 values according to the substrate concentration. The kinetic inhibitory profile of allopurinol was used to validate the XO-ICER. Then, the XO-ICER was used to screen specific ruthenium derivatives. The selected compound, 4CBALO, an allopurinol ruthenium derivative, exhibited 100% inhibition at 200 mM compared to 86% inhibition from allopurinol at the same concentration. The inhibitory effect on the immobilized XO was reversible after the elution of the compound, with immediate recovery of the ICER activity. Additionally, 4CBALO behaved as a selective and competitive tight binder of xanthine oxidase with a true Ki value of 0.29 mM, which was obtained from the Morrison equation. This report describes the first on-flow characterization of tight binders of xanthine oxidasept_BR
dc.identifier.citationRODRIGUES, M. V. N. et al. Characterization and screening of tight binding inhibitors of xanthine oxidase: an on-flow assay. RSC Advances: an international journal to further the chemical sciences, v. 5, p. 37533-37538, 2015. Disponível em: <https://pubs.rsc.org/en/content/articlelanding/2015/ra/c5ra01741f#!divAbstract>. Acesso em: 05 ago. 2017.pt_BR
dc.identifier.doihttps://doi.org/10.1039/C5RA01741F
dc.identifier.issn2046-2069
dc.identifier.urihttp://www.repositorio.ufop.br/handle/123456789/8500
dc.identifier.uri2https://pubs.rsc.org/en/content/articlelanding/2015/ra/c5ra01741f#!divAbstractpt_BR
dc.language.isoen_USpt_BR
dc.rightsrestritopt_BR
dc.titleCharacterization and screening of tight binding inhibitors of xanthine oxidase : an on-flow assay.pt_BR
dc.typeArtigo publicado em periodicopt_BR
Files
Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
ARTIGO_CharacterizationScreeningTight.pdf
Size:
608.79 KB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
924 B
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
DEQUI - Artigos publicados em periódicos