Background: Alzheimer’s Disease (AD) is one of the most prevalent causes of dementia in the world, and no drugs available that can provide a complete cure. Cholinergic neurons of the cerebral cortex of AD patients are lost due to increased activity of cholinesterase enzymes.

Objective: Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) are the two major classes of cholinesterases in the mammalian brain. The involvement of oxidative stress in the progression of AD is known. Thus, the objective of this study is to determine strong ChE inhibitors with anti-oxidant activity.

Methods: In this study, 41 abietane diterpenoids have been assayed for antioxidant and anticholinesterase (both for AChE and BuChE) properties in vitro, which were previously isolated from Salvia species, and structurally determined by spectroscopic methods, particularly intensive 1D- and 2DNMR and mass experiments. Molecular modeling studies were performed to rationalize the in vitro ChE inhibitory activity of several abietane diterpenoids compared with galantamine.

Results: Thirteen out of the tested 41 abietane diterpenoids exhibited at least 50% inhibition on either AChE or BuChE. The strongest inhibitory activity was obtained for Bractealine against BuChE (3.43 μM) and AChE (33.21 μM) while the most selective ligand was found to be Hypargenin E against BuChE enzyme (6.93 μM). A full correlation was not found between anticholinesterase and antioxidant activities. The results obtained from molecular modelling studies of Hypargenin E and Bractealine on AChE and BuChE were found to be in accordance with the in vitro anti-cholinesterase activity tests.

Conclusion: Abietane diterpenoids are promising molecules for the treatment of mild-moderate AD.

中文翻译：

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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。

背景：阿尔茨海默氏病（AD）是全世界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，已经从体外从鼠尾草属物种中分离并通过光谱方法（特别是密集的1D和2DNMR和质谱）测定了41种山茱a的二萜类化合物的体外抗氧化剂和抗胆碱酯酶特性（分别用于AChE和BuChE）。实验。与加兰他敏相比，进行了分子建模研究，以合理化几种松果油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：阿比特尼二萜是治疗轻度中度AD的有前途的分子。