The reactivity of oytho-methoxy-substituted catechol radicals with sulfhydryl groups: Contribution for the comprehension of the mechanism of inhibition of NADPH oxidase by apocynin

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorKanegae, Marilia P. P.
dc.creatorda Fonseca, Luiz Marcos
dc.creatorBrunetti, Iguatemy Lourenço
dc.creatorde Oliveira Silva, Sueli
dc.creatorXimenes, Valdecir Farias
dc.date2014-05-20T13:24:23Z
dc.date2016-10-25T16:45:05Z
dc.date2014-05-20T13:24:23Z
dc.date2016-10-25T16:45:05Z
dc.date2007-08-01
dc.date.accessioned2017-04-05T19:59:54Z
dc.date.available2017-04-05T19:59:54Z
dc.identifierBiochemical Pharmacology. Oxford: Pergamon-Elsevier B.V., v. 74, n. 3, p. 457-464, 2007.
dc.identifier0006-2952
dc.identifierhttp://hdl.handle.net/11449/7538
dc.identifierhttp://acervodigital.unesp.br/handle/11449/7538
dc.identifier10.1016/j.bcp.2007.05.004
dc.identifierWOS:000248259000008
dc.identifierhttp://dx.doi.org/10.1016/j.bcp.2007.05.004
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/856154
dc.descriptionRedox processes are involved in the mechanism of action of NADPH oxidase inhibitors such as diphenyleneiodonium and apocynin. Here, we studied the structure-activity relationship for apocynin and analogous ortho-methoxy-substituted catechols as inhibitors of the NADPH oxidase in neutrophils and their reactivity with peroxidase. Aiming to alter the reduction potential, the ortho-methoxy-catechol moiety was kept constant and the substituents at para position related to the hydroxyl group were varied. Two series of compounds were employed: methoxy-catechols bearing electron-withdrawing groups (MC-W) such as apocynin, vanillin, 4-nitroguaiacol, 4-cyanoguaiacol, and methoxy-catechol bearing electron-donating groups (MC-D) such as 4-methylguaiacol and 4-ethylguaiacol. We found that MC-D were weaker inhibitors compared to MD-W. Furthermore, the radicals generated by oxidation of MC-W via MPO/H(2)O(2), but not for MC-D, were able to oxidize glutathione (GSH) as verified by the formation of thiyl radicals, depletion of GSH, and recycling of the ortho-methoxy-catechols during their oxidations. The capacity of oxidizing sulfhydryl (SH) groups was also verified when ovalbumin was incubated with MC-W, but not for MC-D. Since the effect of apocynin has been correlated with inactivation of the cytosolic fractions of the NADPH oxidase complex and its oxidation during the inhibitory process develops a special role in this process, we suggest that the close relationship between the reactivity of the radicals of MC-W compounds with thiol groups and their efficacy as NADPH oxidase inhibitor could be the chemical pathway behind the mechanism of action of apocynin and should be taken into account in the design of new and specific NADPH oxidase inhibitors. (c) 2007 Elsevier B.V. All rights reserved.
dc.languageeng
dc.publisherElsevier B.V.
dc.relationBiochemical Pharmacology
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectneutrophyl
dc.subjectNADPH oxiclase
dc.subjectmyeloperoxiclase
dc.subjectapocynin
dc.subjectmethoxyr-catechols
dc.subjectsulfhydryl residues
dc.titleThe reactivity of oytho-methoxy-substituted catechol radicals with sulfhydryl groups: Contribution for the comprehension of the mechanism of inhibition of NADPH oxidase by apocynin
dc.typeOtro


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