Ahsan H, Parveen N, Khan N U, Hadi S M
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, India.
Chem Biol Interact. 1999 Jul 1;121(2):161-75. doi: 10.1016/s0009-2797(99)00096-4.
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.
姜黄素是一种天然存在的植物化学物质，赋予姜黄色泽，具有广泛的药理特性，包括抗氧化、抗炎和抗癌作用。我们之前已经表明，姜黄素在铜（II）存在的情况下，通过产生活性氧，特别是羟基自由基，导致DNA链断裂。因此，姜黄素既表现出抗氧化作用，也表现出促氧化作用。为了理解姜黄素各种生物学特性的化学基础，我们研究了姜黄素与其两种天然存在的衍生物，即去甲氧基姜黄素（dmC）和双去甲氧基姜黄素（bdmC）之间的构效关系。发现姜黄素在DNA切割反应中最有效，并且是铜（II）的还原剂，其次是dmC和bdmC。三种姜黄素类化合物产生羟基自由基的速率也呈现出类似的模式。通过研究这些姜黄素类化合物对Fe（II）-EDTA系统（羟基自由基）切割质粒DNA的影响以及核黄素产生单线态氧的影响，检测了它们的相对抗氧化活性。结果表明，姜黄素作为抗氧化剂和氧化DNA切割剂都具有相当高的活性。DNA切割活性是铜（II）与姜黄素分子上不同位点结合的结果。基于目前的结果，我们提出了铜（II）的三个结合位点。其中两个位点由两个苯环上的酚羟基和甲氧基提供，第三个位点是由于环之间存在1,3-二酮系统。此外，姜黄素类化合物的抗氧化和促氧化作用均由相同的结构部分决定。
