title: Design, syntheses, characterization, and cytotoxicity studies of novel heterobinuclear oxindolimine copper(II)-platinum(II) complexes.
abstract: Herein, the design and syntheses of two new mononuclear oxindolimine-copper(II) (1 and 2) and corresponding heterobinuclear oxindolimine Cu(II)Pt(II) complexes (3 and 4), are described. All the isolated complexes were characterized by spectroscopic techniques (UV/Vis, IR, EPR), in addition to elemental analysis and mass spectrometry. Cyclic voltammetry (CV) measurements showed that in all cases, one-electron quasi-reversible waves were observed, and ascribed to the formation of corresponding copper(I) complexes. Additionally, waves related to oxindolimine ligand reduction was verified, and confirmed using analogous oxindolimine-Zn(II) complexes. The Pt(IV/II) reduction, and corresponding oxidation, for complexes 3 and 4 occurred at very close values to those observed for cisplatin. By complementary fluorescence studies, it was shown that glutathione (GSH) cannot reduce any of these complexes, under the experimental conditions (room temperature, phosphate buffer 50mM, pH7.4), using an excess of 20-fold [GSH]. All these complexes showed characteristic EPR spectral profile, with parameters values gǁ>g⊥suggesting an axially distorted environment around the copper(II) center. Interactions with calf thymus-DNA, monitored by circular dichroism (CD), indicated different effects modulated by the ligands. Finally, the cytotoxicity of each complex was tested toward different tumor cells, in comparison to cisplatin, and low values of IC50in the range 0.6 to 4.0μM were obtained, after 24 or 48h incubation at 37°C. The obtained results indicate that such complexes can be promising alternative antitumor agents.
authors: Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Esther Escribano
authors: EE
authors: Aranda
authors: Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Tiago Araújo
authors: TA
authors: Matias
authors: Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Koiti
authors: K
authors: Araki
authors: Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Adriana Pires
authors: AP
authors: Vieira
authors: Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Elaine Andrade
authors: EA
authors: de Mattos
authors: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil; Departamento de Radiologia e Oncologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Pio
authors: P
authors: Colepicolo
authors: Departamento de Radiologia e Oncologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Carolina Portela
authors: CP
authors: Luz
authors: Departamento de Radiologia e Oncologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Fábio Luiz Navarro
authors: FL
authors: Marques
authors: Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address: amdcferr@iq.usp.br.
authors: Ana Maria
authors: AM
authors: da Costa Ferreira
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002417:Cattle; D045744:Cell Line, Tumor; D003300:Copper; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D051379:Mice; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D009944:Organoplatinum Compounds; D003300:Copper; D004247:DNA; C427203:calf thymus DNA
keywords: Copper; Cytotoxicity; Heterobinuclear complexes; Oxindolimine ligands; Platinum; Spectroscopic characterization