Pro-oxidant, anti-oxidant and cleavage activities on DNA of curcumin and its derivatives demethoxycurcumin and bisdemethoxycurcumin
Pro-oxidant, anti-oxidant and cleavage activities on DNA of curcumin and its derivatives demethoxycurcumin and bisdemethoxycurcumin
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DOI：
10.1016/s0009-2797(99)00096-4
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发表时间：
1999-07-01
影响因子：
5.1
通讯作者：
Hadi, SM
中科院分区：
文献类型：
--
作者：
Ahsan, H;Parveen, N;Hadi, SM
姜黄素是一种天然存在的植物化学物质，负责姜黄的颜色，具有广泛的药理学特性，包括抗氧化，抗炎和抗癌作用。我们先前已经表明，姜黄素在Cu（II）的存在下，通过产生活性氧，特别是羟基自由基，导致DNA链断裂。因此，姜黄素显示出抗氧化和促氧化作用。为了了解姜黄素各种生物学性质的化学基础，我们研究了姜黄素及其两种天然衍生物，即脱甲氧基姜黄素（dmC）和双脱甲氧基姜黄素（bdmC）之间的构效关系。姜黄素被认为是最有效的DNA切割反应和还原剂的Cu（II），其次是dmC和bdmC。三种姜黄素类化合物形成羟基自由基的速率也显示出类似的模式。通过研究这些姜黄素类化合物对Fe（II）-EDTA系统（羟基自由基）裂解质粒DNA和核黄素产生单线态氧的影响，检查了相对抗氧化活性。结果表明，姜黄素作为抗氧化剂和氧化DNA裂解剂都具有相当高的活性。DNA切割活性是Cu（II）与姜黄素分子上的各个位点结合的结果。根据目前的研究结果，我们提出了三个结合位点的Cu（II）。其中两个位点由两个苯环上的酚基和甲氧基提供，第三个位点是由于环之间存在1，3-二酮系统。此外，姜黄素的抗氧化剂和促氧化剂作用都是由相同的结构部分决定的。(C)1999爱思唯尔科学爱尔兰有限公司保留所有权利。
Curcumin, a naturally occurring phytochemical responsible for the colour of turmeric shows a wide range of pharmacological properties including antioxidant, anti-inflammatory and anti-cancer effects. We have earlier shown that curcumin in the presence of Cu(II) causes strand cleavage in DNA through generation of reactive oxygen species, particularly the hydroxyl radical. Thus, curcumin shows both antioxidant as well as pro-oxidant effects. In order to understand the chemical basis of various biological properties of curcumin, we have studied the structure-activity relationship between curcumin and its two naturally occurring derivatives namely demethoxycurcumin (dmC) and bisdemethoxycurcumin (bdmC). Curcumin was found to be the most effective in the DNA cleavage reaction and a reducer of Cu(II) followed by dmC and bdmC. The rate of formation of hydroxyl radicals by the three curcuminoids also showed a similar pattern. The relative antioxidant activity was examined by studying the effect of these curcuminoids on cleavage of plasmid DNA by Fe(II)-EDTA system (hydroxyl radicals) and the generation of singlet oxygen by riboflavin. The results indicate that curcumin is considerably more active both as an antioxidant as well as an oxidative DNA cleaving agent. The DNA cleavage activity is the consequence of binding of Cu(II) to various sites on the curcumin molecule. Based on the present results, we propose three binding sites for Cu(II). Two of the sites are provided by the phenolic and methoxy groups on the two benzene rings and the third site is due to the presence of 1,3-diketone system between the rings. Furthermore, both the antioxidant as well as pro-oxidant effects of curcuminoids are determined by the same structural moieties. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.