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Studies of Synthetic Catechin Analogues Useful for Antioxidant Therapy

用于抗氧化治疗的合成儿茶素类似物的研究

基本信息

批准号：
14572105
负责人：
FUKUHARA Kiyoshi
金额：
$ 2.3万
依托单位：
National Institute of Health Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14572105/
关键词：
Antioxidant Reactive Oxygen Species Catechin Polyphenol Flavonoid Cancer

项目摘要

The protective role of antioxidants against free-radical associated diseases has been widely studied and this has prompted the development of new types of antioxidants. A planar catechin analogue (1H_2), in which catechol and chroman moieties in catechin were constrained to be planar, was synthesized via oxa-Pictet Spengler reaction using catechin and aceton with BF_3.Et_2O. The radical-scavenging activities of 1H_2 were examined using galvinoxyl radical (G^・), a stable oxygen-centered radical, showing that the hydrogen transfer reaction from 1H_2 to G^・ is 5-fold faster than that of hydrogen transfer from the native catechin to G^・. The kinetics of hydrogen transfer from catechins to cumylperoxyl radical was also examined in propionitrile (EtCN) at low temperature with use of ESR, showing that the rate of hydrogen transfer from P1H_2 is significantly faster than that from catechin. Under basic conditions, the dianion (1^<2->) of 1H_2 reduced molecular oxygen to produce superoxide anion (O_2^<・->). However, the electron transfer rate was slower than that of catechin, suggesting that 1H_2 may be a promising novel antioxidant with reduced pro-oxidant activity. The 1H_2 also showed an enhanced protective effect against the oxidative DNA damage induced by Fenton reaction without the pro-oxidant effect, which is usually observed in the case of the native catechin.Finally, the planar catechin acalogue showed the strong radical scavenging ability and reduced prooxidant effect responsible for the less-efficient generation of O_2^<・->. The completed inhibition of DNA strand scission is also expected the efficient protection toward oxidative damage of biopolymers caused by the reactive oxygen species. The lipophilic property of 1H_2 is also useful for suppressing free-radical associated event, especially in the cell membrane. Therefore, 1H_2 might be very effective for the prevention and/or treatment of free radical-associated diseases.

抗氧化剂对自由基相关疾病的保护作用已被广泛研究，这促进了新型抗氧化剂的开发。以儿茶素和丙酮为原料，BF 3·Et 2 O为催化剂，通过oxa-Pictet Spengler反应，合成了一种儿茶素平面类似物（1H 2）。用galvinoxyl自由基（G^·）测定了1H_2的自由基清除活性，结果表明，1H_2向G^·的氢转移反应比天然儿茶素向G^·的氢转移反应快5倍。用ESR研究了低温下在丙腈（EtCN）中儿茶素与枯基过氧化氢自由基的氢转移动力学，表明P1H_2的氢转移速率明显快于儿茶素。在碱性条件下，1H_2的二价阴离子（1^<2->）还原分子氧生成超氧阴离子（O_2^·->）。但电子传递速率比儿茶素慢，表明1H_2可能是一种具有较低促氧化活性的新型抗氧化剂。1H_2对芬顿反应诱导的DNA氧化损伤也有增强的保护作用，但没有天然儿茶素的促氧化作用，最后，平面儿茶素乙酰化酶具有较强的自由基清除能力，但其促氧化作用减弱，导致O_2^·->生成效率降低。对DNA链断裂的完全抑制也有望有效地保护由活性氧引起的生物聚合物的氧化损伤。1H_2的亲脂性也可用于抑制自由基相关事件，尤其是在细胞膜中。因此，1H_2可能是预防和/或治疗自由基相关疾病的有效药物。