Prooxidant activity of aminophenol compounds: copper-dependent generation of reactive oxygen species.

ABSTRACT

Prooxidant properties of aminophenol, the constituent of acetaminophen and mesalamine, were examined. Aminophenol compounds/copper-dependent formation of reactive oxygen species was analyzed by the inactivation of aconitase, the most sensitive enzyme to oxidative stress in permeabilized yeast cells. Aminophenol compounds of 2 (ortho)- and 4 (para)- substituents, but not 3 (meta)-isomer produced reactive oxygen species in the presence of copper (cupric) ion or iron. The inactivation required sodium azide the inhibitor of catalase, suggesting that the superoxide radical produced from the 2- and 4-aminophenol in the presence of copper is responsible for the inactivation of aconitase. Aminophenols of 2- and 4-substituents showed a potent reducing activity of copper (cupric) ion, and further potent reactivity with DPPH radical, but 3-aminophenol showed only a little reactivity. Reduced copper ion can generate superoxide radical with the production of oxidized metal. Aminophenols can reduce the copper ion, and further stimulate the continuous production of reactive oxygen species. Cytotoxic effect of acetaminophen, the N-acetylated-p-aminophenol and mesalamine, the 4-aminophenol derivatives may be accounted for by the prooxidant properties of their constituents, aminophenol.