title: Correlation between DNA interactions and cytotoxic activity of four new ternary compounds of copper(II) with N-donor heterocyclic ligands.
abstract: Four new ternary complexes of copper(II) were synthesized and characterized: [Cu(hyd)(bpy)(acn)(ClO4)](ClO4)] (1), [Cu(hyd)(phen)(acn)(ClO4)](ClO4)] (2), [Cu(Shyd)(bpy)(acn)(ClO4)](ClO4)] (3) and [Cu(Shyd)(phen)(acn)(ClO4)](ClO4)] (4), in which acn=acetonitrile; hyd=2-furoic acid hydrazide, bpy=2,2-bipyridine; phen=1,10-phenanthroline and Shyd=2-thiophenecarboxylic acid hydrazide. The cytotoxic activity of the complexes in a chronic myelogenous leukemia cell line was investigated. All complexes are able to enter cells and inhibit cellular growth in a concentration-dependent manner, with an activity higher than that of the corresponding free ligands. The substitution of Shyd for hyd increases the activity, while the substitution of bpy for phen renders the complex less active. Therefore, the most potent complex is 4 with an IC50 value of 1.5±0.2μM. The intracellular copper concentration needed to inhibit 50% of cell growth is approximately 7×10(-15)mol/cell. It is worth notifying that a correlation between cytotoxic activity, DNA binding affinity and DNA cleavage was found: 1<3<2<4.
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil.
authors.forename: Priscila P
authors.initials: PP
authors.lastname: Silva
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil.
authors.forename: Wendell
authors.initials: W
authors.lastname: Guerra
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil.
authors.forename: Geandson Coelho
authors.initials: GC
authors.lastname: Dos Santos
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil.
authors.forename: Nelson G
authors.initials: NG
authors.lastname: Fernandes
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil.
authors.forename: Josiane N
authors.initials: JN
authors.lastname: Silveira
authors.affiliation: Instituto de Química, Universidade de São Paulo, 05508-000, São Paulo, Brazil.
authors.forename: Ana M
authors.initials: AM
authors.lastname: da Costa Ferreira
authors.affiliation: Centro de Biologia Molecular Estrutural, Departamento de Bioquímica, Universidade Federal de Santa Catarina, 88040-970, Florianópolis-SC, Brazil.
authors.forename: Tiago
authors.initials: T
authors.lastname: Bortolotto
authors.affiliation: Centro de Biologia Molecular Estrutural, Departamento de Bioquímica, Universidade Federal de Santa Catarina, 88040-970, Florianópolis-SC, Brazil.
authors.forename: Hernán
authors.initials: H
authors.lastname: Terenzi
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, 88040-970, Florianópolis-SC, Brazil.
authors.forename: Adailton João
authors.initials: AJ
authors.lastname: Bortoluzzi
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, 88040-970, Florianópolis-SC, Brazil.
authors.forename: Ademir
authors.initials: A
authors.lastname: Neves
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, Brazil. Electronic address: elene@qui.ufmg.br.
authors.forename: Elene C
authors.initials: EC
authors.lastname: Pereira-Maia
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D003300:Copper / Q000737:chemistry* / Q000633:toxicity*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D006131:Growth Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D008024:Ligands; D008958:Models, Molecular; D009584:Nitrogen / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D006131:Growth Inhibitors; D006571:Heterocyclic Compounds; D008024:Ligands; D003300:Copper; D004247:DNA; D009584:Nitrogen
keywords: Cellular concentration; Cytotoxicity; DNA binding; DNA cleavage; Ternary copper compounds