Synthesis, Characterization, DNA Binding and Cytotoxicity of Copper(II) Phenylcarboxylate Complexes
Carlos Y. Fernández,
Analu Rocha,
Mohammad Azam,
Natalia Alvarez,
Kim Min,
Alzir A. Batista,
Antonio J. Costa-Filho,
Javier Ellena,
Gianella Facchin
Affiliations
Carlos Y. Fernández
Química Inorgánica, Departamento Estrella Campos, Facultad de Química, Universidad de la República, Montevideo 11800, Uruguay
Analu Rocha
Departamento de Química, Federal University of São Carlos, CP 676, São Carlos 13565-905, SP, Brazil
Mohammad Azam
Department of Chemistry, College of Sciences, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
Natalia Alvarez
Química Inorgánica, Departamento Estrella Campos, Facultad de Química, Universidad de la República, Montevideo 11800, Uruguay
Kim Min
Department of Safety Engineering, Dongguk University, 123 Dongdae-ro, Gyeongju 780714, Gyeongbuk, Republic of Korea
Alzir A. Batista
Departamento de Química, Federal University of São Carlos, CP 676, São Carlos 13565-905, SP, Brazil
Antonio J. Costa-Filho
Physics Department, Ribeirão Preto School of Philosophy, Science and Literature, University of São Paulo, Av. Bandeirantes, Ribeirão Preto 14040-901, SP, Brazil
Javier Ellena
São Carlos Institute of Physics, University of São Paulo, Av. do Trabalhador São-Carlense 400, São Carlos 13566-590, SP, Brazil
Gianella Facchin
Química Inorgánica, Departamento Estrella Campos, Facultad de Química, Universidad de la República, Montevideo 11800, Uruguay
Coordination compounds of copper exhibit cytotoxic activity and are suitable for the search for novel drug candidates for cancer treatment. In this work, we synthesized three copper(II) carboxylate complexes, [Cu2(3-(4-hydroxyphenyl)propanoate)4(H2O)2]·2H2O (C1), [Cu2(phenylpropanoate)4(H2O)2] (C2) and [Cu2(phenylacetate)4] (C3), and characterized them by elemental analysis and spectroscopic methods. Single-crystal X-ray diffraction of C1 showed the dinuclear paddle-wheel arrangement typical of Cu–carboxylate complexes in the crystal structure. In an aqueous solution, the complexes remain as dimeric units, as studied by UV-visible spectroscopy. The lipophilicity (partition coefficient) and the DNA binding (UV visible and viscosity) studies evidence that the complexes bind the DNA with low Kb constants. In vitro cytotoxicity studies on human cancer cell lines of metastatic breast adenocarcinoma (MDA-MB-231, MCF-7), lung epithelial carcinoma (A549) and cisplatin-resistant ovarian carcinoma (A2780cis), as well as a nontumoral lung cell line (MRC-5), indicate that the complexes are cytotoxic in cisplatin-resistant cells.
