Alzheimer's disease (AD) is a neurodegenerative disorder. Substrate-specific Acetylcholinesterase (AChE) plays a vital role in the AD treatment. Flavonoids with AChE inhibitory activities and low toxicity are used to developing new anti-AD agents. In this study, the best 3D QSAR pharmacophore model Hypo1 was generated by HypoGen program in Discovery Studio2016 based on the training set of flavonoids. We performed a virtual screening from Traditional Chinese Medicine (TCM), Druglike and MiniMaybridge databases using Hypo1. From docking analyses, we got the top 10 AChE inhibitors which were further evaluated by 8 different scoring functions. De Novo Evolution designed the top 10 derivatives, and three potential AChE inhibitor candidates were obtained eventually.

阿尔茨海默氏病（AD）是一种神经退行性疾病。底物特异性乙酰胆碱酯酶（AChE）在AD治疗中起着至关重要的作用。具有AChE抑制活性和低毒性的类黄酮用于开发新型抗AD药物。在这项研究中，最佳3D QSAR药效团模型Hypo1是由Discovery Studio2016中的HypoGen程序基于类黄酮的训练集生成的。我们使用Hypo1从中药（TCM），Druglike和MiniMaybridge数据库中进行了虚拟筛选。通过对接分析，我们获得了排名前10位的AChE抑制剂，并通过8种不同的评分功能对其进行了进一步评估。De Novo Evolution设计了前十大衍生物，最终获得了三个潜在的AChE抑制剂候选物。