4 '-Aminochalcones As Novel Inhibitors of the Chlorinating Activity of Myeloperoxidase

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dc.contributor.authorZeraik, M. L. [UNESP]
dc.contributor.authorXimenes, V. F. [UNESP]
dc.contributor.authorRegasini, L. O. [UNESP]
dc.contributor.authorDutra, L. A. [UNESP]
dc.contributor.authorSilva, Dulce Helena Siqueira [UNESP]
dc.contributor.authorFonseca, L. M. [UNESP]
dc.contributor.authorCoelho, D.
dc.contributor.authorMachado, S. A. S.
dc.contributor.authorBolzani, Vanderlan da Silva [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2014-05-20T15:30:46Z
dc.date.available2014-05-20T15:30:46Z
dc.date.issued2012-11-01
dc.description.abstractThe excessive activation of neutrophils generates reactive oxygen species (ROS) and the secretion of primary granular enzymes, such as myeloperoxidase (MPO), which is implicated in numerous inflammatory diseases. The aim of this study was to evaluate chalcones as inhibitors of the chlorinating activity of MPO using in vitro and ex vivo assays. In addition to cytotoxic properties, the inhibition of respiratory burst, the scavenger capacity, and the oxidation potential were measured. 4'-Aminochalcone (1), 4'-amino-4-fluorochalcone (2), and 4'-amino-4-methylchalcone (3) exhibited potent inhibition of the chlorinating activity of MPO, as evaluated in a neutrophil system and a free cell system, to the following degree: (1) IC50 = 0.265 +/- 0.036 mu ol L-1; (2) IC50 = 0.250 +/- 0.081 mu ol L-1; and (3) IC50 = 0.250 +/- 0.012 mu ol L-1. These values were similar to those for 5-fluorotryptamine (IC50 = 0.192 +/- 0.012 mu ol L-1), a compound considered to be a potent MPO inhibitor. These aminochalcones were not toxic to neutrophils at concentrations below 100 mu ol L-1, as determined by the trypan blue exclusion assay. Compounds 1-3 presented a high oxidation potential (E-pa1 approximate to 0.80 V), low scavenger capacity against DPPH center dot and HOCl, and low inhibition of respiratory burst. These data indicated that aminochalcones are potent inhibitors of MPO chlorinating activity, a new property for chalcone derivatives, given that they are neither antioxidant agents nor inhibitors of respiratory burst. In conclusion, the selected aminochalcones have potential as pharmacological agents for inflammatory diseases.en
dc.description.affiliationSão Paulo State Univ UNESP, Dept Organ Chem, Inst Chem, Nuclei Bioassays Ecophysiol & Biosynth Nat Prod N, BR-14800900 São Paulo, Brazil
dc.description.affiliationSão Paulo State Univ UNESP, Fac Sci, Dept Chem, BR-17033360 São Paulo, Brazil
dc.description.affiliationSão Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Clin Anal, BR-14801902 São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Inst Chem, BR-13560970 São Carlos, SP, Brazil
dc.description.affiliationUnespSão Paulo State Univ UNESP, Dept Organ Chem, Inst Chem, Nuclei Bioassays Ecophysiol & Biosynth Nat Prod N, BR-14800900 São Paulo, Brazil
dc.description.affiliationUnespSão Paulo State Univ UNESP, Fac Sci, Dept Chem, BR-17033360 São Paulo, Brazil
dc.description.affiliationUnespSão Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Clin Anal, BR-14801902 São Paulo, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdFAPESP: 11/03017-6
dc.description.sponsorshipIdFAPESP: 10/52327-5
dc.format.extent5405-5413
dc.identifierhttp://dx.doi.org/10.2174/092986712803833344
dc.identifier.citationCurrent Medicinal Chemistry. Sharjah: Bentham Science Publ Ltd, v. 19, n. 31, p. 5405-5413, 2012.
dc.identifier.doi10.2174/092986712803833344
dc.identifier.issn0929-8673
dc.identifier.lattes4702004904231248
dc.identifier.lattes4484083685251673
dc.identifier.orcid0000-0002-1516-7765
dc.identifier.urihttp://hdl.handle.net/11449/40084
dc.identifier.wosWOS:000310598500010
dc.language.isoeng
dc.publisherBentham Science Publ Ltd
dc.relation.ispartofCurrent Medicinal Chemistry
dc.relation.ispartofjcr3.469
dc.relation.ispartofsjr1,015
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectAnti-inflammatoryen
dc.subjectantioxidanten
dc.subjectchalconesen
dc.subjecthypochlorous aciden
dc.subjectmyeloperoxidase inhibitionen
dc.subjectneutrophilsen
dc.subjectaminochalconesen
dc.subjectreactive oxygen speciesen
dc.subjectredox potentialen
dc.subjectscavenger capacityen
dc.title4 '-Aminochalcones As Novel Inhibitors of the Chlorinating Activity of Myeloperoxidaseen
dc.typeResenha
dcterms.licensehttp://www.benthamscience.com/permission.php
dcterms.rightsHolderBentham Science Publ Ltd
unesp.author.lattes4702004904231248
unesp.author.lattes4484083685251673
unesp.author.lattes4702004904231248[5]
unesp.author.orcid0000-0002-1516-7765[5]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Química, Araraquarapt
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Ciências Farmacêuticas, Araraquarapt

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