2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone therapy
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1590/S0100-879X2012007500078 http://hdl.handle.net/11449/8706 |
Resumo: | Apatone™, a combination of menadione (2-methyl-1,4-naphthoquinone, VK3) and ascorbic acid (vitamin C, VC) is a new strategy for cancer treatment. Part of its effect on tumor cells is related to the cellular pro-oxidative imbalance provoked by the generation of hydrogen peroxide (H2O2) through naphthoquinone redox cycling. In this study, we attempted to find new naphthoquinone derivatives that would increase the efficiency of H2O2 production, thereby potentially increasing its efficacy for cancer treatment. The presence of an electron-withdrawing group in the naphthoquinone moiety had a direct effect on the efficiency of H2O2 production. The compound 2-bromo-1,4-naphthoquinone (BrQ), in which the bromine atom substituted the methyl group in VK3, was approximately 10- and 19-fold more efficient than VK3 in terms of oxygen consumption and H2O2 production, respectively. The ratio [H2O2]produced / [naphthoquinone]consumed was 68 ± 11 and 5.8 ± 0.2 (µM/µM) for BrQ and VK3, respectively, indicating a higher efficacy of BrQ as a catalyst for the autoxidation of ascorbic acid. Both VK3 and BrQ reacted with glutathione (GSH), but BrQ was the more effective substrate. Part of GSH was incorporated into the naphthoquinone, producing a nucleophilic substitution product (Q-SG). The depletion of BrQ by GSH did not prevent its redox capacity since Q-SG was also able to catalyze the production of reactive oxygen species. VK3/VC has already been submitted to clinical trials for the treatment of prostate cancer and has demonstrated promising results. However, replacement of VK3 with BrQ will open new lines of investigation regarding this approach to cancer treatment. |
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2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone therapyCancerApatoneAscorbic acidHydrogen peroxide2-Bromo-1,4-naphthoquinoneApatone™, a combination of menadione (2-methyl-1,4-naphthoquinone, VK3) and ascorbic acid (vitamin C, VC) is a new strategy for cancer treatment. Part of its effect on tumor cells is related to the cellular pro-oxidative imbalance provoked by the generation of hydrogen peroxide (H2O2) through naphthoquinone redox cycling. In this study, we attempted to find new naphthoquinone derivatives that would increase the efficiency of H2O2 production, thereby potentially increasing its efficacy for cancer treatment. The presence of an electron-withdrawing group in the naphthoquinone moiety had a direct effect on the efficiency of H2O2 production. The compound 2-bromo-1,4-naphthoquinone (BrQ), in which the bromine atom substituted the methyl group in VK3, was approximately 10- and 19-fold more efficient than VK3 in terms of oxygen consumption and H2O2 production, respectively. The ratio [H2O2]produced / [naphthoquinone]consumed was 68 ± 11 and 5.8 ± 0.2 (µM/µM) for BrQ and VK3, respectively, indicating a higher efficacy of BrQ as a catalyst for the autoxidation of ascorbic acid. Both VK3 and BrQ reacted with glutathione (GSH), but BrQ was the more effective substrate. Part of GSH was incorporated into the naphthoquinone, producing a nucleophilic substitution product (Q-SG). The depletion of BrQ by GSH did not prevent its redox capacity since Q-SG was also able to catalyze the production of reactive oxygen species. VK3/VC has already been submitted to clinical trials for the treatment of prostate cancer and has demonstrated promising results. However, replacement of VK3 with BrQ will open new lines of investigation regarding this approach to cancer treatment.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Estadual Paulista Faculdade de Ciências Departamento de QuímicaUniversidade Estadual Paulista Faculdade de Ciências Farmacêuticas Departamento de Análises ClínicasUniversidade Estadual Paulista Faculdade de Ciências Departamento de QuímicaUniversidade Estadual Paulista Faculdade de Ciências Farmacêuticas Departamento de Análises ClínicasAssociação Brasileira de Divulgação Científica (ABRADIC)Universidade Estadual Paulista (Unesp)Graciani, F. S. [UNESP]Ximenes, Valdecir Farias [UNESP]2014-05-20T13:26:49Z2014-05-20T13:26:49Z2012-08-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article701-710application/pdfhttp://dx.doi.org/10.1590/S0100-879X2012007500078Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 45, n. 8, p. 701-710, 2012.0100-879Xhttp://hdl.handle.net/11449/870610.1590/S0100-879X2012007500078S0100-879X2012000800003WOS:000307713400003S0100-879X2012000800003.pdf4066413997908572SciELOreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBrazilian Journal of Medical and Biological Research1.492info:eu-repo/semantics/openAccess2024-04-29T18:17:00Zoai:repositorio.unesp.br:11449/8706Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-04-29T18:17Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone therapy |
title |
2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone therapy |
spellingShingle |
2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone therapy Graciani, F. S. [UNESP] Cancer Apatone Ascorbic acid Hydrogen peroxide 2-Bromo-1,4-naphthoquinone |
title_short |
2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone therapy |
title_full |
2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone therapy |
title_fullStr |
2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone therapy |
title_full_unstemmed |
2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone therapy |
title_sort |
2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone therapy |
author |
Graciani, F. S. [UNESP] |
author_facet |
Graciani, F. S. [UNESP] Ximenes, Valdecir Farias [UNESP] |
author_role |
author |
author2 |
Ximenes, Valdecir Farias [UNESP] |
author2_role |
author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Graciani, F. S. [UNESP] Ximenes, Valdecir Farias [UNESP] |
dc.subject.por.fl_str_mv |
Cancer Apatone Ascorbic acid Hydrogen peroxide 2-Bromo-1,4-naphthoquinone |
topic |
Cancer Apatone Ascorbic acid Hydrogen peroxide 2-Bromo-1,4-naphthoquinone |
description |
Apatone™, a combination of menadione (2-methyl-1,4-naphthoquinone, VK3) and ascorbic acid (vitamin C, VC) is a new strategy for cancer treatment. Part of its effect on tumor cells is related to the cellular pro-oxidative imbalance provoked by the generation of hydrogen peroxide (H2O2) through naphthoquinone redox cycling. In this study, we attempted to find new naphthoquinone derivatives that would increase the efficiency of H2O2 production, thereby potentially increasing its efficacy for cancer treatment. The presence of an electron-withdrawing group in the naphthoquinone moiety had a direct effect on the efficiency of H2O2 production. The compound 2-bromo-1,4-naphthoquinone (BrQ), in which the bromine atom substituted the methyl group in VK3, was approximately 10- and 19-fold more efficient than VK3 in terms of oxygen consumption and H2O2 production, respectively. The ratio [H2O2]produced / [naphthoquinone]consumed was 68 ± 11 and 5.8 ± 0.2 (µM/µM) for BrQ and VK3, respectively, indicating a higher efficacy of BrQ as a catalyst for the autoxidation of ascorbic acid. Both VK3 and BrQ reacted with glutathione (GSH), but BrQ was the more effective substrate. Part of GSH was incorporated into the naphthoquinone, producing a nucleophilic substitution product (Q-SG). The depletion of BrQ by GSH did not prevent its redox capacity since Q-SG was also able to catalyze the production of reactive oxygen species. VK3/VC has already been submitted to clinical trials for the treatment of prostate cancer and has demonstrated promising results. However, replacement of VK3 with BrQ will open new lines of investigation regarding this approach to cancer treatment. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-08-01 2014-05-20T13:26:49Z 2014-05-20T13:26:49Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1590/S0100-879X2012007500078 Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 45, n. 8, p. 701-710, 2012. 0100-879X http://hdl.handle.net/11449/8706 10.1590/S0100-879X2012007500078 S0100-879X2012000800003 WOS:000307713400003 S0100-879X2012000800003.pdf 4066413997908572 |
url |
http://dx.doi.org/10.1590/S0100-879X2012007500078 http://hdl.handle.net/11449/8706 |
identifier_str_mv |
Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 45, n. 8, p. 701-710, 2012. 0100-879X 10.1590/S0100-879X2012007500078 S0100-879X2012000800003 WOS:000307713400003 S0100-879X2012000800003.pdf 4066413997908572 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Brazilian Journal of Medical and Biological Research 1.492 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
701-710 application/pdf |
dc.publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica (ABRADIC) |
publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica (ABRADIC) |
dc.source.none.fl_str_mv |
SciELO reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799965032865333248 |