Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China.
Bioorg Chem. 2018 Feb;76:400-414. doi: 10.1016/j.bioorg.2017.12.015. Epub 2017 Dec 6.
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黄酮类化合物被用于开发新的抗 AD 药物。在这项研究中，基于黄酮类化合物的训练集，HypoGen 程序在 Discovery Studio2016 中生成了最佳的 3D QSAR 药效团模型 Hypo1。我们使用 Hypo1 对中药（TCM）、Druglike 和 MiniMaybridge 数据库进行了虚拟筛选。通过对接分析，我们得到了 top10 的 AChE 抑制剂，然后进一步使用 8 种不同的打分函数对其进行评估。从头进化设计了 top10 的衍生物，最终得到了三个有潜力的 AChE 抑制剂候选物。
