Synthesis, structure and biological activity of a new and efficient Cd(II)-uracil derivative complex system for cleavage of DNA.
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.
Illán-Cabeza
Nuria A
NA
Departamento de Química Orgánica e Inorgánica, Facultad de Ciencias Experimentales, Universidad de Jaén, 23071, Jaén, Spain.
Vilaplana
Rosario A
RA
Alvarez
Ysmael
Y
Akdi
Khalid
K
Kamah
Sanae
S
Hueso-Ureña
Francisco
F
Quirós
Miguel
M
González-Vílchez
Francisco
F
Moreno-Carretero
Miguel N
MN
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002104:Cadmium / Q000737:chemistry; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage; D004586:Electrophoresis; D006801:Humans; D015394:Molecular Structure; D009942:Organometallic Compounds; D010957:Plasmids / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014498:Uracil / Q000737:chemistry
D000970:Antineoplastic Agents; C507911:Cd(II)-2,6-bis(1-(4-amino-1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxopyrimidin-5-yl)imino)ethylpyridine; D009942:Organometallic Compounds; D002104:Cadmium; D014498:Uracil; D004247:DNA; C427203:calf thymus DNA