title: Copper(I)-Phosphine Polypyridyl Complexes: Synthesis, Characterization, DNA/HSA Binding Study, and Antiproliferative Activity.
abstract: A series of copper(I)-phosphine polypyridyl complexes have been investigated as potential antitumor agents. The complexes [Cu(PPh3)2dpq]NO3(2), [Cu(PPh3)2dppz]NO3(3), [Cu(PPh3)2dppa]NO3(4), and [Cu(PPh3)2dppme]NO3(5) were synthesized by the reaction of [Cu(PPh3)2NO3] with the respective planar ligand under mild conditions. These copper complexes were fully characterized by elemental analysis, molar conductivity, FAB-MS, and NMR, UV-vis, and IR spectroscopies. Interactions between these copper(I)-phosphine polypyridyl complexes and DNA have been investigated using various spectroscopic techniques and analytical methods, such as UV-vis titrations, thermal denaturation, circular dichroism, viscosity measurements, gel electrophoresis, and competitive fluorescent intercalator displacement assays. The results of our studies suggest that these copper(I) complexes interact with DNA in an intercalative way. Furthermore, their high protein binding affinities toward human serum albumin were determined by fluorescence studies. Additionally, cytotoxicity analyses of all complexes against several tumor cell lines (human breast, MCF-7; human lung, A549; and human prostate, DU-145) and non-tumor cell lines (Chinese hamster lung, V79-4; and human lung, MRC-5) were performed. The results revealed that copper(I)-phosphine polypyridyl complexes are more cytotoxic than the corresponding planar ligand and also showed to be more active than cisplatin. A good correlation was observed between the cytostatic activity and lipophilicity of the copper(I) complexes studied here.
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos , CEP 13565-905 São Carlos, SP, Brazil.
authors.forename: Wilmer
authors.identifier: http://orcid.org/0000-0002-7781-4083
authors.initials: W
authors.lastname: Villarreal
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos , CEP 13565-905 São Carlos, SP, Brazil.
authors.forename: Legna
authors.initials: L
authors.lastname: Colina-Vegas
authors.affiliation: Diretoria de Metrologia Aplicada às Ciências da Vida, Instituto Nacional de Metrologia, Qualidade e Tecnologia , CEP 25250-020 Xerém, RJ, Brazil.|Centro de Desenvolvimento Tecnológico em Saúde (CDTS), Fundação Oswaldo Cruz - Fiocruz , CEP 21040-361 Rio de Janeiro, RJ, Brazil.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Visbal
authors.affiliation: Centro de Química, Instituto Venezolano de Investigaciones Científicas (IVIC) , Carretera Panamericana Km. 11, Apartado 20632, Altos de Pipe, 1020A Estado Miranda, Venezuela.
authors.forename: Oscar
authors.initials: O
authors.lastname: Corona
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos , CEP 13565-905 São Carlos, SP, Brazil.|ICEB, Departamento de Química, Universidade Federal de Ouro Preto , CEP 35400-000 Ouro Preto, MG, Brazil.
authors.forename: Rodrigo S
authors.initials: RS
authors.lastname: Corrêa
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo , CEP 13560-970 São Carlos, SP, Brazil.
authors.forename: Javier
authors.initials: J
authors.lastname: Ellena
authors.affiliation: Departamento de Gerontología, Universidade Federal de São Carlos , CEP 13565-905 São Carlos, SP, Brazil.
authors.forename: Marcia Regina
authors.initials: MR
authors.lastname: Cominetti
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos , CEP 13565-905 São Carlos, SP, Brazil.
authors.forename: Alzir Azevedo
authors.initials: AA
authors.lastname: Batista
authors.affiliation: Diretoria de Metrologia Aplicada às Ciências da Vida, Instituto Nacional de Metrologia, Qualidade e Tecnologia , CEP 25250-020 Xerém, RJ, Brazil.
authors.forename: Maribel
authors.initials: M
authors.lastname: Navarro
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry*; D003412:Cricetulus; D004247:DNA / Q000737:chemistry*; D024202:Electrophoretic Mobility Shift Assay; D005453:Fluorescence; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D010720:Phosphines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010957:Plasmids / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012709:Serum Albumin / Q000737:chemistry*; D044366:Transition Temperature
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D007364:Intercalating Agents; D008024:Ligands; D010720:Phosphines; D011725:Pyridines; D012709:Serum Albumin; D003300:Copper; D004247:DNA; D002945:Cisplatin