人类乙酰胆碱酯酶（ACHE）与抑制剂小分子的对接研究

阿尔茨海默病（Alzheimer’s disease，AD）是一种中枢神经系统致死性神经原发性退行病变，是老年痴呆症中最常见的一种类型．乙酰胆碱酯酶抑制剂（AChEI）是目前治疗AD的主要药物．我们选择他克林、利伐斯的明、石杉碱甲、在研药物TV-3326、多奈哌齐和Anseculin，分别与AChE进行分子对接研究．结果表明：抑制剂与AChE结合能力的大小顺序为：他克林〈利伐斯的明〈石杉碱甲〈TV．3326〈多奈哌齐〈Anseculin，这与实验中测得ACHE1的IC50值反应活性大小一致．上述6类药物分子，Anseculin与AChE的相互作用能力最强．

Theoretical studies of interaction models of human acetylcholine esterase with different inhibitors

Alzheimer＇s disease （AD） is a progressive neurodegenerative disorder and one of the most common causes of dementia in the elderly. Acetylcholine esterase inhibitors （AChEI） are the main drugs used in the treatment of AD. In this work, docking studies have been performed in order to understand the interaction between a number of inhibitors （tacrine, rivastigmine, huperzine A, TV-3326 （ladostigil）, donepezil and anseculin） and acetylcholine esterase （ACHE）. The calculated binding affinities between inhibitors and AChE increase in the order tacrine 〈rivastigmine 〈 huperzine A 〈 TV-3326 〈 donepezil 〈 anseculin, which reflects the experimental inhibitory activity expressed in terms of the half maximal inhibitory concentration （the IC50 value）. Of the above inhibitors, anseeulin is the most useful drug for the treatment of dementia.