title: New copper(I) and heteronuclear copper(I)-ruthenium(II) complexes: Synthesis, structural characterization and cytotoxicity.
abstract: A new family of copper(I) complexes of general formula [Cu(dppe)(NN)]+have been synthesized and fully characterized, with dppe=1.2-bis(diphenylphosphino)ethane and NN representing several bidentate heteroaromatic ligands: 2,2'-bipy=2.2'-bipyridine (1), Me2bpy=4.4'-dimethyl-2,2'-bipyridine (2), dpytz=3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine (3), dpp=2.3-bis(2-pyridyl)pyrazine (4), and the metallaligand [Ru(η5-C5H5)(PPh3)(dpp)]+(5), yielding the bimetallic copper(I)-ruthenium(II) complex [Cu(dppe)(μ-dpp)Ru(η5-C5H5)(PPh3)]2+(6). The single crystal structures of complexes (2) and (4) were determined by X-ray diffraction studies. All the complexes exhibit high cytotoxicity against the human cancer cells A2780 and MCF7 with IC50values far lower than those found for the antitumor drug cisplatin in the same cell lines and even surpassing cisplatin resistance in the A2780cisR cells. They display IC50values on the human embryonic kidney HEK293 non-tumoral cells of the same order of magnitude as those found for the tumoral cells. In the ovarian cells the compounds induce rapid production of reactive oxygen species (ROS) probably through mitochondrial pathways. According to the results reported here, these compounds can be considered as prospective antitumoral agents that deserve further evaluation.
authors.affiliation: Centro de Química Estrutural, Faculdade de Ciências, Universidade de Lisboa, Portugal; Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Lopes
authors.affiliation: Centro de Química Estrutural, Faculdade de Ciências, Universidade de Lisboa, Portugal; Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Portugal.
authors.forename: David
authors.initials: D
authors.lastname: Alves
authors.affiliation: Centro de Química Estrutural, Faculdade de Ciências, Universidade de Lisboa, Portugal; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal; Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Portugal. Electronic address: tsmorais@ciencias.ulisboa.pt.
authors.forename: Tânia S
authors.initials: TS
authors.lastname: Morais
authors.affiliation: Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Portugal; Centro de Química e Bioquímica, DQB, Faculdade de Ciências, Universidade de Lisboa, Portugal.
authors.forename: Paulo J
authors.initials: PJ
authors.lastname: Costa
authors.affiliation: Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Portugal; Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Portugal.
authors.forename: M Fátima M
authors.initials: MF
authors.lastname: Piedade
authors.affiliation: Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Portugal.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Marques
authors.affiliation: Centro de Química Estrutural, Faculdade de Ciências, Universidade de Lisboa, Portugal; Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Portugal. Electronic address: mjbrito@ciencias.ulisboa.pt.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Villa de Brito
authors.affiliation: Centro de Química Estrutural, Faculdade de Ciências, Universidade de Lisboa, Portugal; Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Helena Garcia
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D012428:Ruthenium / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D003300:Copper; D012428:Ruthenium
keywords: Copper(I); Cytotoxicity; Heteronuclear complex; Ruthenium(II); X-ray diffraction