Synthesis, structural characterization, cytotoxic properties and DNA binding of a dinuclear copper(II) complex

• Published in: Journal of inorganic biochemistry 2016-08, Vol.161, p.9-17
• Main Authors: Ferreira, B.J.M. Leite, Brandão, P., Meireles, M., Martel, Fátima, Correia-Branco, Ana, Fernandes, Diana M., Santos, T.M., Félix, V.
• Format: Article
• Language: English
• Subjects: Adenine; Caco-2; Copper - chemistry; Copper - pharmacology; Cytotoxins - chemical synthesis; Cytotoxins - chemistry; Cytotoxins - pharmacology; Dinuclear copper(II) complex; DNA - metabolism; DNA-binding; HeLa; HeLa Cells; Humans; Phenanthroline; Phenanthrolines - chemical synthesis; Phenanthrolines - chemistry; Phenanthrolines - pharmacology
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2016.04.026

In this study a novel dinuclear copper(II) complex with adenine and phenanthroline has been synthesized and its structure determined by single crystal X-ray diffraction. In the dinuclear complex [Cu₂(μ-adenine)₂(phen)₂(H2O)2](NO3)4·0.5H2O (phen=1,10-phenanthroline) (1) the two Cu(II) centres exhibit a distorted square pyramidal coordination geometry linked by two nitrogen donors from adenine bridges leading to a Cu–Cu distance of 3.242(3)Å. Intramolecular and intermolecular π⋯π interactions as well as an H-bonding network were observed. The antitumor capacity of the complex has been tested in vitro against human cancer cell lines, cervical carcinoma (HeLa) and colorectal adenocarcinoma (Caco-2), by metabolic tests, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide as reagent. The complex 1 has remarkable low IC50 values of 0.87±0.06μM (HeLa) and 0.44±0.06μM (Caco-2), when compared with values for cisplatin against the same cell lines. The interaction of complex 1 with calf thymus DNA (CT DNA) was further investigated by absorption and fluorescence spectroscopic methods. A binding constant of 5.09×105M−1 was obtained from UV–vis absorption studies. “A novel dinuclear Cu(II) complex containing both adenine and 1,10-phenanthroline has been designed, synthesized, characterized and evaluated for is in vitro anticancer activity. The complex was identified as a potent anti-proliferative agent against HeLa and Caco-2 cancer cells — IC50 values of 0.870±0.06 and 0.44±0.06μM were determined by metabolic tests.” [Display omitted] •Dicopper(II) adenine/phenanthroline complex (1) was synthesized.•The structure was determined by single crystal X-ray diffraction.•The complex 1 has remarkable IC50 values of 0.87±0.06μM (HeLa) and 0.44±0.06μM (Caco-2).•The Cu(II) complex interacts with calf thymus DNA via the intercalation mode.