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当代阿耳茨海默病研究

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

天然Abietane二萜类化合物的抗胆碱酯酶和抗氧化活性的分子对接研究

卷 17, 期 3, 2020

页: [269 - 284] 页: 16

弟呕挨: 10.2174/1567205017666200424133534

价格: $65

摘要

背景：阿尔茨海默氏病（AD）是世界上痴呆症最普遍的病因之一，目前尚无可完全治愈的药物。 AD患者大脑皮质的胆碱能神经元由于胆碱酯酶的活性增加而丢失。目的：乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）是哺乳动物脑中的两大类胆碱酯酶。氧化应激参与AD的进展是已知的。因此，本研究的目的是确定具有抗氧化活性的强ChE抑制剂。 方法：在这项研究中，已经从体外从丹参属物种中分离出41种Abietane二萜类化合物的抗氧化剂和抗胆碱酯酶（分别用于AChE和BuChE）特性进行了测定，并通过光谱法对其结构进行了测定，特别是密集的1D和2DNMR和质量实验。与加兰他敏相比，进行了分子建模研究，以合理化几种Abetanee二萜类化合物的体外ChE抑制活性。 结果：在测试的41种Abietane二萜类化合物中，有13种对AChE或BuChE表现出至少50％的抑制作用。对Bractealine的BuChE（3.43μM）和AChE（33.21μM）具有最强的抑制活性，而选择性最强的配体是HyBugenin E对BuChE酶（6.93μM）。在抗胆碱酯酶和抗氧化活性之间未发现完全相关。从Hypargenin E和Bractealine对AChE和BuChE进行分子建模研究获得的结果被发现与体外抗胆碱酯酶活性测试一致。 结论：Abietane二萜是治疗轻度中度AD的有前途的分子。

关键词: 阿尔茨海默病，胆碱酯酶抑制，乙酰胆碱酯酶，丁酰胆碱酯酶，抗氧化剂，对接研究，阿比坦二萜类化合物，萨尔维亚。

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