title: Copper(II) complexes with tridentate pyrazole-based ligands: synthesis, characterization, DNA cleavage activity and cytotoxicity.
abstract: Tridentate pyrazole-containing ligands of the Schiff base type, SalPz - HL(1), Cl(2)SalPz - HL(2) and I(2)SalPz - HL(3), were used to prepare a series of new Cu(II) complexes (CuSalPz - 1, CuCl(2)SalPz - 2 and CuI(2)SalPz - 3). These new complexes have been studied by different analytical techniques (electrospray ionization mass spectrometry (ESI-MS), elemental analysis, FT-IR and EPR). The spectroscopic properties of 1-3 are consistent with the formation of Cu(II) complexes coordinated by monoanionic and tridentate (N,N,O)-chelators, behaving as monomeric species in aqueous solution, as shown by EPR studies. Crystals of 2 and 3, obtained by slow concentration of methanolic solutions of the compounds, were also analyzed by X-ray diffraction analysis. The X-ray structural study has shown that 2 crystallized as a dinuclear compound, [Cu(2)(μ-Cl)(2)(Cl(2)SalPz)(2)], while the solid state structure determined for 3 is best described by monomeric units of [CuCl(I(2)SalPz)] displaying short Cu···Cl intermolecular contacts. The in vitro evaluation of 1-3 comprised the study of their DNA-cleaving ability using plasmid DNA and the assessment of their cytotoxic activity against several human cancer cell lines (PC-3 prostate, MCF-7 breast and A2780 and A2780cisR-ovary). The studies with plasmid DNA have shown that 2 and 3 induce extensive DNA cleavage in the presence of different additives. The cytotoxic activity of 2 and 3 is comparable to the one presented by cisplatin, with the exception of the A2780 cell line where cisplatin is more active. It has been found that the introduction of halogen substituents in the phenolate rings of the chelators enhanced the cytotoxicity of the respective Cu(II) complexes.
authors: Unidade de Ciências Químicas e Radiofarmacêuticas, Instituto Tecnológico e Nuclear Estrada Nacional 10, Sacavém, Portugal.
authors: Sofia
authors: S
authors: Gama
authors: Filipa
authors: F
authors: Mendes
authors: Fernanda
authors: F
authors: Marques
authors: Isabel C
authors: IC
authors: Santos
authors: M Fernanda
authors: MF
authors: Carvalho
authors: Isabel
authors: I
authors: Correia
authors: João Costa
authors: JC
authors: Pessoa
authors: Isabel
authors: I
authors: Santos
authors: António
authors: A
authors: Paulo
mesh_terms: D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D053837:DNA Cleavage; D006801:Humans; D008024:Ligands; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry*; D012545:Schiff Bases / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D002614:Chelating Agents; D056831:Coordination Complexes; D008024:Ligands; D011720:Pyrazoles; D012545:Schiff Bases; C560567:chloro(N-(2-hydroxy-3,5-dichloride-benzyl-2-pyrazolethyl)iminate)copper(II); C560568:chloro(N-(2-hydroxy-3,5-diiodine-benzyl-2-pyrazolethyl)iminate)copper(II); C031280:pyrazole; D003300:Copper; D004247:DNA