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- Title
Synthesis, structure and biological activity of a new and efficient Cd(II)–uracil derivative complex system for cleavage of DNA.
- Authors
Illán-Cabeza, Nuria; Vilaplana, Rosario; Alvarez, Ysmael; Akdi, Khalid; Kamah, Sanae; Hueso-Ureña, Francisco; Quirós, Miguel; González-Vílchez, Francisco; Moreno-Carretero, Miguel
- Abstract
The new complex formed by Cd(II) and the 1:2 Schiff-base-type ligand 2,6-bis[1-(4-amino-1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxopyrimidin-5-yl)imino]ethylpyridine (DAPDAAU) has been chemically and structurally characterized by X-ray diffraction: the ion Cd(II) is surrounded by six nitrogen atoms from two DAPDAAU ligands which coordinates each one in a tridentate fashion through the pyridine ring (N1) and both azomethine nitrogen atoms (N5). The interaction of the Cd(II) complex (compound I) with calf-thymus DNA as observed by circular dichroism spectroscopy suggests the initial unwinding of the DNA double helix strongly depends on increasing incubation times and metal-to-nucleic acid molar ratios. Electrophoretic experiments indicate that the cadmium complex induces cleavage of the plasmid pBR322 DNA to give ulterior nicking and shortening of this molecule, as a result of the complex binding to DNA, resulting in the conclusion that compound I behaves as a chemical nuclease. Cytotoxic activity of the Cd(II) complex against selected different human cancer cell lines is specific and increases with increasing concentration of the metal compound; this fact indicates the potential antitumor character of the complex. When the culture medium is supplemented with compound I, a remarkable inhibition of the growing cell is observed, important cell degeneration appears before 48 h and abundant precipitates are formed that correspond to cell residues and denatured proteins.
- Subjects
CADMIUM; DNA; ANTINEOPLASTIC agents; ANTIBODY-dependent cell cytotoxicity; SCHIFF bases; CONDENSATION products (Chemistry); LIGANDS (Biochemistry); PYRIDINE; ELECTROPHORESIS
- Publication
Journal of Biological Inorganic Chemistry (JBIC), 2005, Vol 10, Issue 8, p924
- ISSN
0949-8257
- Publication type
Article
- DOI
10.1007/s00775-005-0045-x