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AutorNeves, Amanda P.
AutorPereira, Michelle X. G.
AutorPeterson, Erica J.
AutorKipping, Ralph
AutorVargas, Maria D.
AutorSilva Jr., Floriano P.
AutorFarrell, Nicholas P.
Fecha de acceso2016-01-01T14:23:16Z
Fecha de disponibilización2016-01-01T14:23:16Z
Fecha de publicación2013
ReferenciaNEVES, Amanda P.; et al. Exploring the DNA binding/cleavage, cellular accumulation and topoisomerase inhibition of 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinone Mannich bases and their platinum(II) complexes. Journal of Inorganic Biochemistry, v.119, p.54–64, Feb. 2013.pt_BR
ISSN0162-0134
URIhttps://www.arca.fiocruz.br/handle/icict/12470
Idiomaengpt_BR
EditorElsevierpt_BR
Derechos de autorrestricted access
TítuloExploring the DNA binding/cleavage, cellular accumulation and topoisomerase inhibition of 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinone Mannich bases and their platinum(II) complexespt_BR
Tipo del documentoArticle
DOI10.1016/j.jinorgbio.2012.10.007
Resumen en InglésSeveral chlorido and amino Pt2+ complexes of 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinone Mannich bases HL exhibiting moderate to high cytotoxicity against cancer cell lines were studied in order to investigate theirmodes of DNA binding, in vitro DNA strand breaks, mechanismof topoisomerase (Topo I) inhibition and cellular accumulation. DNA model base studies have shown that complex 1a [Pt(HL1)Cl2] was capable of binding covalently to 9-ethylguanine (9-EtG) and 5′-GMP. 1H NMR and mass spectrometry studies have shown that both chlorides were substituted by 9-EtG ligands, whereas 5′-GMP was able to replace only one chlorido ligand, due to steric hindrance. The chlorido Pt2+ complexes [Pt(HL)Cl2] highly accumulate in prostate (PC-3) and melanoma (MDA-MB-435) cell lines, being able to induce DNA strand breaks in vitro and inhibit Topo I by a catalytic mode. On the other hand, the free 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinones HL and the amino Pt2+ complexes [Pt(L−)(NH3)2]NO3 neither cause DNA strand breakage nor exhibit strongDNA interaction, nevertheless the latter were also found to be catalytic inhibitors of Topo I at 100 μM. Thus, coordination of the Mannich bases HL to the “PtCl2” fragment substantially affects the chemical and biophysical properties of the pro-ligands, leading to an improvement of their DNA binding properties and generating compounds that cleave DNA and catalytically inhibit Topo I. Finally, the high cytotoxicity exhibited by the free (uncomplexed) 2-hydroxy-3-(aminomethyl)-1,4-naphthoquinones might be associated with their decomposition in solution, which is not observed for the Pt2+ complexes.pt_BR
AfiliaciónVirginia Commonwealth University. Department of Chemistry. Richmond, VA, USA.pt_BR
AfiliaciónFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Proteínas e Peptídeos. Rio de Janeiro, RJ, Brasil.pt_BR
AfiliaciónVirginia Commonwealth University. Department of Chemistry. Richmond, VA, USA.pt_BR
AfiliaciónVirginia Commonwealth University. Department of Chemistry. Richmond, VA, USA.pt_BR
AfiliaciónUniversidade Federal Fluminense, Campus do Valonguinho. Instituto de Química. Niterói, RJ, Brasil.pt_BR
AfiliaciónFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Proteínas e Peptídeos. Rio de Janeiro, RJ, Brasil.pt_BR
AfiliaciónUniversidade Federal Fluminense, Campus do Valonguinho. Instituto de Química. Niterói, RJ, Brasil.pt_BR
AfiliaciónVirginia Commonwealth University. Department of Chemistry. Richmond, VA, USA.pt_BR
Palavras clave en InglêsNaphthoquinonept_BR
Palavras clave en InglêsPt2+ complexespt_BR
Palavras clave en InglêsDNA bindingpt_BR
Palavras clave en InglêsDNA strand breakspt_BR


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