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Heterobinuclear copper(II)­platinum(II) complexes with oxindolimine ligands: Interactions with DNA, and inhibition of kinase and alkaline phosphatase proteins.
Aranda, Esther Escribano; da Luz, Juliana Silva; Oliveira, Carla Columbano; Divina Petersen, Philippe A; Petrilli, Helena M; da Costa Ferreira, Ana M.
Afiliação
  • Aranda EE; Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, São Paulo 05508-000, SP, Brazil.
  • da Luz JS; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo 05508-000, SP, Brazil.
  • Oliveira CC; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo 05508-000, SP, Brazil.
  • Divina Petersen PA; Departamento de Física dos Materiais e Mecânica, Instituto de Física, Universidade de São Paulo, 05508-090 São Paulo, SP, Brazil.
  • Petrilli HM; Departamento de Física dos Materiais e Mecânica, Instituto de Física, Universidade de São Paulo, 05508-090 São Paulo, SP, Brazil.
  • da Costa Ferreira AM; Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, São Paulo 05508-000, SP, Brazil. Electronic address: amdcferr@iq.usp.br.
J Inorg Biochem ; 203: 110863, 2020 02.
Article em En | MEDLINE | ID: mdl-31683126
Two mononuclear copper(II) compounds, [Cu(isad)(H2O)Cl]Cl 1 and [Cu(isah)(H2O)Cl]Cl 2, and its corresponding heterobinuclear species containing also platinum(II), [CuCl(isad)Pt(NH3)Cl2] 3 and [CuCl(isah)Pt(NH3)Cl2] 4 (where isad and isah are oxindolimine ligands, (E)-3-(2-(3-aminopropylamino)ethylimino)indolin-2-one, and (E)-3-(3-amino-2-hydroxypropylimino)indolin-2-one, respectively), have been previously synthesized and characterized by different spectroscopic techniques in our laboratory. Cytotoxicity assays performed with B16F10 murine cancer cells, and MES-SA human uterine sarcoma cells, showed IC50 values lower or in the same order of cisplatin. Herein, in order to better elucidate their probable modes of action, possible interaction and damage to DNA, as well as their effect on the activity of crucial proteins were verified. Both mononuclear complexes and the binuclear compound 4 displayed a significant cleavage activity toward plasmid DNA, while compound 3 tends to protect DNA from oxidative damage, avoiding degradation. Complementary experiments indicated a significant inhibition activity toward cyclin-dependent kinase (CDK1/cyclinB) activity in the phosphorylation of histone H1, and only moderate inhibition concerning alkaline phosphatase. Results also revealed that the reactivity is reliant on the ligand structure and on the nature of the metal present, in a synergistic effect. Simulation studies complemented and supported our results, indicating different bindings of the binuclear compounds to DNA. Therefore, the verified cytotoxicity of these complexes comprises multiple modes of action, including modification of DNA conformation, scission of DNA strands by reactive oxygen species, and inhibition of selected proteins that are crucial to the cellular cycle.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA / Inibidores de Proteínas Quinases / Fosfatase Alcalina / Complexos de Coordenação / Oxindóis / Iminas Limite: Animals / Humans Idioma: En Revista: J Inorg Biochem Ano de publicação: 2020 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: DNA / Inibidores de Proteínas Quinases / Fosfatase Alcalina / Complexos de Coordenação / Oxindóis / Iminas Limite: Animals / Humans Idioma: En Revista: J Inorg Biochem Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos