Antioxidative effects of curcumin and its analogues against the free-radical-induced peroxidation of linoleic acid in micelles.

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, 1) is a yellow ingredient isolated from turmeric (curcumin longa). Many health benefits have been claimed for curcumin, and these have generally been ascribed to its radical-trapping antioxidant properties. In order to find more active antioxidants with 1 as the lead compound, we synthesized curcumin analogues, i.e., 1,7-bis(3,4-dihydroxyphenyl)-1,6-heptadiene-3,5-dione (2), 1-(3,4-dihydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (3), 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (4), 1,7-bis (4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (5), 1,7-bis(3,4-dimethoxyphenyl)-1,6-heptadiene-3,5-dione (6), 1,7-bis(4-methoxyphenyl)-1,6-heptadiene-3,5-dione (7), and 1,7-diphenyl-1,6-heptadiene-3,5-dione (8). Antioxidative effects of curcumin and these analogues against the peroxidation of linoleic acid were studied in sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB) micelles. The peroxidation was initiated thermally by a water-soluble initiator 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), and reaction kinetics were monitored by the formation of linoleic acid hydroperoxides. Kinetic analysis of the antioxidation process demonstrates that these compounds, except 6, 7 and 8, are effective antioxidants in micelles by H-atom abstraction from the phenolic groups. Compounds 2 and 3, which bear ortho-diphenoxyl functionality, possess significantly higher antioxidant activity than curcumin and other analogues, and the 4-hydroxy-3-methoxyphenyl group also plays an important role in the antioxidative activity. In addition, the synergistic antioxidant effect of these compounds with alpha-tocopherol (vitamin E) in micelles was also studied by following the formation of linoleic acid hydroperoxides and the consumption of alpha-tocopherol. It was found that these compounds could not synergistically interact with alpha-tocopherol in micelles.