Activities of flavonoids for the cleavage of DNA in the presence of Cu(II): correlation with generation of active oxygen species.

Abstract

The activities of several flavonoids and the related nonflavonoid compound epicatechin were compared with respect to Cu(II)-induced strand scission of DNA by using two different assays. The same series of compounds was used to study the stoichiometry of Cu(II) reduction in the absence of DNA. The compounds were compared for their ability to generate superoxide, hydrogen peroxide and the Cu(II)-dependent production of hydroxyl radicals. Flavonoids were examined to assess the production of a charge-transfer complex with Cu and the rate of decay of the complexes were compared. All the compounds tested had some ability to cause DNA strand scission in the presence of Cu(II), with myricetin being the most active and galangin the least active. The ability to cause such scission correlated with the rate of decay of the charge-transfer complex, the ability to generate active oxygen species and with the stoichiometry of Cu(II) binding. Analysis of the data in the light of the structural differences between the flavonoids led to a discussion of alternative Cu(II)-sequestering mechanisms.