Binding affinity of Cu(II)-VP-16 (etoposide) complex and its analogues to DNA and hydroxyl radical generation during DNA strand breaks

R Tawa; D Gao; M Takami; Y Imakura; K H Lee; H Sakurai

doi:10.1016/s0968-0896(98)00049-2

Binding affinity of Cu(II)-VP-16 (etoposide) complex and its analogues to DNA and hydroxyl radical generation during DNA strand breaks

Bioorg Med Chem. 1998 Jul;6(7):1003-8. doi: 10.1016/s0968-0896(98)00049-2.

Authors

R Tawa¹, D Gao, M Takami, Y Imakura, K H Lee, H Sakurai

Affiliation

¹ Department of Analytical & Bioinorganic Chemistry, Kyoto Pharmaceutical University, Japan.

PMID: 9730236
DOI: 10.1016/s0968-0896(98)00049-2

Abstract

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.

MeSH terms

Animals
Antineoplastic Agents, Phytogenic / chemistry*
Cattle
Circular Dichroism
Copper / chemistry*
DNA Damage*
Etoposide / chemistry*
Hydroxyl Radical / chemistry*
Kinetics
Oxidation-Reduction

Substances

Antineoplastic Agents, Phytogenic
Hydroxyl Radical
Etoposide
Copper
cupric chloride