Binding affinity of Cu(II)-VP-16 (etoposide) complex and its analogues to DNA and hydroxyl radical generation during DNA strand breaks.
Conformational effects and affinities of VP-16 (etoposide) and its derivatives to DNA in the presence of Cu(II) ion were examined by circular dichroic (CD) spectra. The Cu(II)/Cu(I) redox kinetics and the hydroxyl radical (.OH) generation from the Cu(II)-complexes were estimated by the stopped-flow kinetics. Based on the results, DNA-cleaving activity of Cu(II)-complexes of VP-16 has been shown to be related with binding affinity of the complex to DNA, Cu(II)/Cu(I) redox and .OH generation, emphasising the mechanism of generated .OH attack to DNA.
Tawa
R
R
Department of Analytical & Bioinorganic Chemistry, Kyoto Pharmaceutical University, Japan.
Gao
D
D
Takami
M
M
Imakura
Y
Y
Lee
K H
KH
Sakurai
H
H
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D002417:Cattle; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry*; D004249:DNA Damage; D005047:Etoposide / Q000737:chemistry*; D017665:Hydroxyl Radical / Q000737:chemistry*; D007700:Kinetics; D010084:Oxidation-Reduction
D000972:Antineoplastic Agents, Phytogenic; D017665:Hydroxyl Radical; D005047:Etoposide; D003300:Copper; C029892:cupric chloride