Inhibition of lipid peroxidation and protein oxidation in rat liver mitochondria by curcumin and its analogues.
Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, 1) is a yellow ingredient isolated from turmeric (curcumin longa). It has been shown to exhibit a variety of biological activities including antioxidative activity. In order to find more active antioxidants with 1 as the lead compound we synthesized curcumin analogues, i.e., 1-(3,4-dihydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (2), 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (3), 1,7-bis-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (4), 1-(3,4-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (5), 1,7-bis(3,4-dimethoxyphenyl)-1,6-heptadiene-3,5-dione (6), and 1,7-diphenyl-1,6-heptadiene-3,5-dione (7), and evaluated their antioxidative activity. The in vitro oxidative damage to both lipids and proteins in rat liver mitochondria was used as a model to study the free radical-induced oxidative damage of biological lipids as well as proteins and the protective effects of these curcumin analogues. It was found that these compounds, except 6 and 7, could effectively inhibit the free radical induced lipid peroxidation and protein oxidative damage of rat liver mitochondria by H-atom abstraction from the phenolic groups. Compound 2 which bear ortho-diphenoxyl functionality exhibited remarkably higher antioxidative activity for lipids and proteins than curcumin and other analogues, and the 4-hydroxy-3-methoxyphenyl group also play an important role in the antioxidative activity.
Wei
Qing-Yi
QY
National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730,000, China.
Chen
Wei-Feng
WF
Zhou
Bo
B
Yang
Li
L
Liu
Zhong-Li
ZL
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008930:Mitochondria, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D017392:Thiobarbituric Acid Reactive Substances
D000975:Antioxidants; D011506:Proteins; D017392:Thiobarbituric Acid Reactive Substances; D003474:Curcumin