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Reactivity of dinuclear copper(II) complexes towards melanoma cells: Correlation with its stability, tyrosinase mimicking and nuclease activity.
Nunes, Cléia Justino; Borges, Beatriz Essenfelder; Nakao, Lia Sumie; Peyroux, Eugénie; Hardré, Renaud; Faure, Bruno; Réglier, Marius; Giorgi, Michel; Prieto, Marcela Bach; Oliveira, Carla Columbano; Da Costa Ferreira, Ana M.
Afiliação
  • Nunes CJ; Departamento de Química, Instituto de Química, Universidade de São Paulo, 05508-000 São Paulo, SP, Brazil.
  • Borges BE; Departamento de Patologia Básica, Universidade Federal do Paraná, 81531-990 Curitiba, PR, Brazil.
  • Nakao LS; Departamento de Patologia Básica, Universidade Federal do Paraná, 81531-990 Curitiba, PR, Brazil.
  • Peyroux E; Aix Marseille Université, Centrale Marseille, CNRS, ISM2 UMR 7313, 13397 Marseille, France.
  • Hardré R; Aix Marseille Université, Centrale Marseille, CNRS, ISM2 UMR 7313, 13397 Marseille, France.
  • Faure B; Aix Marseille Université, Centrale Marseille, CNRS, ISM2 UMR 7313, 13397 Marseille, France.
  • Réglier M; Aix Marseille Université, Centrale Marseille, CNRS, ISM2 UMR 7313, 13397 Marseille, France.
  • Giorgi M; Aix Marseille Université, CNRS, Spectropole FR1739, 13397 Marseille, France.
  • Prieto MB; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-000 São Paulo, SP, Brazil.
  • Oliveira CC; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-000 São Paulo, SP, Brazil.
  • Da Costa Ferreira AM; Departamento de Química, Instituto de Química, Universidade de São Paulo, 05508-000 São Paulo, SP, Brazil. Electronic address: amdcferr@iq.usp.br.
J Inorg Biochem ; 149: 49-58, 2015 Aug.
Article em En | MEDLINE | ID: mdl-26021698
In this work, the influence of two new dinuclear copper(II) complexes in the viability of melanoma cells (B16F10 and TM1MNG3) was investigated, with the aim of verifying possible correlations between their cytotoxicity and their structure. One of the complexes had a polydentate dinucleating amine-imine ligand (complex 2), and the other a tridentate imine and a diamine-bridging ligand (complex 4). The analogous mononuclear copper(II) species (complexes 1 and 3, respectively) were also prepared for comparative studies. Crystal structure determination of complex 2 indicated a square-based pyramidal geometry around each copper, coordinated to three N atoms from the ligand and the remaining sites being occupied by either solvent molecules or counter-ions. Complex 4 has a tetragonal geometry. Interactions of these complexes with human albumin protein (HSA) allowed an estimation of their relative stabilities. Complementary studies of their reactivity towards DNA indicated that all of them are able of causing significant oxidative damage, with single and double strand cleavages, in the presence of hydrogen peroxide. However, nuclease activity of the dinuclear species was very similar and much higher than that of the corresponding mononuclear compounds. Although complex 2, with a more flexible structure, exhibits a much higher tyrosinase activity than complex 4, having a more rigid environment around the metal ion, both complexes showed comparable cytotoxicity towards melanoma cells. Corresponding mononuclear complexes showed to be remarkably less reactive as tyrosinase mimics as well as cytotoxic agents. Moreover, the dinuclear complexes showed higher cytotoxicity towards more melanogenic cells. The obtained results indicated that the structure of these species is decisive for its activity towards the malignant tumor cells tested.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Monofenol Mono-Oxigenase / Cobre / Desoxirribonucleases / Complexos de Coordenação / Antineoplásicos Limite: Humans Idioma: En Revista: J Inorg Biochem Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Monofenol Mono-Oxigenase / Cobre / Desoxirribonucleases / Complexos de Coordenação / Antineoplásicos Limite: Humans Idioma: En Revista: J Inorg Biochem Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos