Wei Qing-Yi, Chen Wei-Feng, Zhou Bo, Yang Li, Liu Zhong-Li
National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730,000, China.
Biochim Biophys Acta. 2006 Jan;1760(1):70-7. doi: 10.1016/j.bbagen.2005.09.008. Epub 2005 Oct 3.
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.
姜黄素（1,7-双（4-羟基-3-甲氧基苯基）-1,6-庚二烯-3,5-二酮，1）是从姜黄（姜黄属）中分离出的一种黄色成分。已证明它具有多种生物活性，包括抗氧化活性。为了以1为先导化合物寻找更具活性的抗氧化剂，我们合成了姜黄素类似物，即1-（3,4-二羟基苯基）-7-（4-羟基-3-甲氧基苯基）-1,6-庚二烯-3,5-二酮（2）、1-（4-羟基-3-甲氧基苯基）-7-（4-羟基苯基）-1,6-庚二烯-3,5-二酮（3）、1,7-双（4-羟基苯基）-1,6-庚二烯-3,5-二酮（4）、1-（3,4-二甲氧基苯基）-7-（4-羟基-3-甲氧基苯基）-1,6-庚二烯-3,5-二酮（5）、1,7-双（3,4-二甲氧基苯基）-1,6-庚二烯-3,5-二酮（6）和1,7-二苯基-1,6-庚二烯-3,5-二酮（7），并评估了它们的抗氧化活性。以大鼠肝线粒体中脂质和蛋白质的体外氧化损伤为模型，研究自由基诱导的生物脂质以及蛋白质的氧化损伤以及这些姜黄素类似物的保护作用。结果发现，除6和7外，这些化合物可通过从酚基团夺取氢原子，有效抑制自由基诱导的大鼠肝线粒体脂质过氧化和蛋白质氧化损伤。具有邻二酚氧基官能团的化合物2对脂质和蛋白质表现出比姜黄素及其他类似物显著更高的抗氧化活性，并且4-羟基-3-甲氧基苯基在抗氧化活性中也起重要作用。
