The triad indole-3-acetic acid ethyl ester/esterase/horseradish peroxidase as a new cytotoxic prodrug/enzyme combination

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dc.contributor.authorPereira, Débora Helena [UNESP]
dc.contributor.authorKitagawa, Rodrigo Rezende [UNESP]
dc.contributor.authorRaddi, Maria Stella Gonçalves [UNESP]
dc.contributor.authorFonseca, Luiz Marcos da [UNESP]
dc.contributor.authorXimenes, Valdecir Farias [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2016-01-28T16:56:18Z
dc.date.available2016-01-28T16:56:18Z
dc.date.issued2010
dc.description.abstractThe antibody-directed enzyme prodrug therapy (ADEPT) is a means of restricting the action of toxic drugs to the tumor site. The enzyme/prodrug pair horseradish peroxidase (HRP)/indole-3-acetic acid (IAA) has been studied as a combination with potential application in ADEPT strategies. In this combination, the non-toxic plant hormone IAA is activated to cytotoxic species by the catalytic action of HRP. Objective: We studied the use of the ethyl ester of IAA as a new prodrug that could be activated by two enzymes, HRP and esterase. Methods: The oxidation of IAA and its ethyl ester, catalyzed by HRP, was monitored by the consumption of dioxygen and liquid chromatography. The cytotoxicity of IAA and its ethyl ester in combination with HRP and esterase was assessed using the lineage McCoy cells through the trypan blue and neutral red assays. Results: We found that HRP was not able to catalyze the oxidation of IAA-ethyl ester in the absence of an additional esterase. Hence, the potential cytotoxicity of the IAA-ethyl ester could be controlled by sequential treatment with esterase, to liberate the carboxyl group, and HRP, for oxidation and generation of cytotoxic species. We present evidence for the potential application of the combination IAA-ethyl ester/esterase/horseradish peroxidase as a new ADEPT, GDEPT or related strategy. Conclusions: We suggest that this technique could provide more selectivity in the generation of cytotoxic drugs at tumor sites.en
dc.description.affiliationUniversidade Estadual Paulista Júlio de Mesquita Filho, Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas de Araraquara, Araraquara, Rua Expedicionários do Brasil, 1621, Centro, CEP 14801-902, SP, Brasil
dc.description.affiliationUniversidade Estadual Paulista Júlio de Mesquita Filho, Departamento de Quimica, Faculdade de Ciências, Bauru-Brasil
dc.description.affiliationUnespUniversidade Estadual Paulista Júlio de Mesquita Filho, Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas de Araraquara, Araraquara, Rua Expedicionários do Brasil, 1621, Centro, CEP 14801-902, SP, Brasil
dc.description.affiliationUnespUniversidade Estadual Paulista Júlio de Mesquita Filho, Departamento de Quimica, Faculdade de Ciências, Bauru-Brasil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent204-209
dc.identifierhttp://www.appliedcr.org.br/detalhe_artigo.asp?id=42
dc.identifier.citationApplied Cancer Research, v. 30, n. 1, p. 204-209, 2010.
dc.identifier.issn1808-5512
dc.identifier.lattes4064204116589015
dc.identifier.lattes4419635633356792
dc.identifier.lattes4424075292014459
dc.identifier.lattes4066413997908572
dc.identifier.urihttp://hdl.handle.net/11449/133716
dc.language.isoeng
dc.relation.ispartofApplied Cancer Research
dc.rights.accessRightsAcesso restrito
dc.sourceCurrículo Lattes
dc.subjectIndole-3-acetic acid synthaseen
dc.subjectIndole-3-acetic acid ethyl esteren
dc.subjectHorseradish peroxidaseen
dc.subjectEsterasesen
dc.titleThe triad indole-3-acetic acid ethyl ester/esterase/horseradish peroxidase as a new cytotoxic prodrug/enzyme combinationen
dc.typeArtigo
unesp.author.lattes4064204116589015
unesp.author.lattes4419635633356792
unesp.author.lattes4424075292014459
unesp.author.lattes4066413997908572
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Ciências Farmacêuticas, Araraquarapt
unesp.departmentAnálises Clínicaspt

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Artigos - Análises Clínicas - FCFAR
Artigos - Química - FC