Pro-oxidant, anti-oxidant and cleavage activities on DNA of curcumin and its derivatives demethoxycurcumin and bisdemethoxycurcumin

Abstract

Curcumin, a naturally occurring phytochemical responsible for the colour of turmeric shows a wide range of pharmacological properties including antioxidant, anti-inflammatory and anti-cancer effects. We have earlier shown that curcumin in the presence of Cu(II) causes strand cleavage in DNA through generation of reactive oxygen species, particularly the hydroxyl radical. Thus, curcumin shows both antioxidant as well as pro-oxidant effects. In order to understand the chemical basis of various biological properties of curcumin, we have studied the structure-activity relationship between curcumin and its two naturally occurring derivatives namely demethoxycurcumin (dmC) and bisdemethoxycurcumin (bdmC). Curcumin was found to be the most effective in the DNA cleavage reaction and a reducer of Cu(II) followed by dmC and bdmC. The rate of formation of hydroxyl radicals by the three curcuminoids also showed a similar pattern. The relative antioxidant activity was examined by studying the effect of these curcuminoids on cleavage of plasmid DNA by Fe(II)-EDTA system (hydroxyl radicals) and the generation of singlet oxygen by riboflavin. The results indicate that curcumin is considerably more active both as an antioxidant as well as an oxidative DNA cleaving agent. The DNA cleavage activity is the consequence of binding of Cu(II) to various sites on the curcumin molecule. Based on the present results, we propose three binding sites for Cu(II). Two of the sites are provided by the phenolic and methoxy groups on the two benzene rings and the third site is due to the presence of 1,3-diketone system between the rings. Furthermore, both the antioxidant as well as pro-oxidant effects of curcuminoids are determined by the same structural moieties.