Structure-activity relationships for the inhibition of lipid peroxidation and the scavenging of free radicals by synthetic symmetrical curcumin analogues

A number of ring substituted analogues of curcumin were synthesized. Their antioxidant properties were studied using three models, inhibition of lipid peroxidation, scavenging of 1,1'-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethyl-benzthiazoline-6-sulphonate radical (ABTS(+.)). In all the models, the phenolic analogues were more active than the non-phenolic analogues, some of which were inactive. The highest antioxidant activity was obtained when the phenolic group was sterically hindered by the introduction of two methyl groups at the ortho position. This and several other compounds were more active than the standard antioxidants alpha-tocopherol and trolox. This study has demonstrated that the phenolic group is important for the antioxidant activity of curcumin and that the structural features that enhance the antioxidant properties of phenols are optimized in curcumin to a significant extent.