Reactions of reactive oxygen species (ROS) with curcumin analogues: Structure-activity relationship

Three curcumin analogues viz., bisdemethoxy curcumin, monodemethoxy curcumin, and dimethoxycurcumin that differ at the phenolic substitution were synthesized. These compounds have been subjected for free radical reactions with DPPH radicals, superoxide radicals (O-2(center dot-)), singlet oxygen (O-1(2)) and peroxyl radicals (CCl3O2 center dot) and the bimolecular rate constants were determined. The DPPH radical reactions were followed by stopped-flow spectrometer, O-1(2) reactions by transient luminescence spectrometer, and CCl3O2 center dot reactions using pulse radiolysis technique. The rate constants indicate that the presence of o-methoxy phenolic OH increases its reactivity with DPPH and CCl3O2 center dot, while for molecules lacking phenolic OH, this reaction is very sluggish. Reaction of O-2(center dot-) and O-1(2) with curcumin analogues takes place preferably at beta-diketone moiety. The studies thus suggested that both phenolic OH and the beta-diketone moiety of curcumin are involved in neutralizing the free radicals and their relative scavenging ability depends on the nature of the free radicals.