Zhu Yong, Tong Xin-Yue, Zhao Yue, Chen Hui, Jiang Feng-Chao
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Yao Xue Xue Bao. 2008 Mar;43(3):267-76.
Based on ninety three acetylcholinesterase inhibitors (AChEIs) which have the same mechanism of action but are different in structural characteristics, the pharmacophore model for acetylcholinesterase inhibitor was constructed by the CATALYST system. The optimal pharmacophore model with three hydrophobic units, a ring aromatic unit and a hydrogen-bond acceptor unit were confirmed (Weight = 3.29, RMS = 0.53, total cost-null cost = 62.75, Correl = 0.93, Config = 19.05). This pharmacophore model will act on the double active site of acetylcholinesterase and is able to predict the activity of known acetylcholinesterase inhibitors that are used for clinical treatment of Alzheimer's disease (AD), and can be further used to identify structurally diverse compounds that have higher activity treating with Alzheimer's disease (AD) by virtual screening.
基于93种作用机制相同但结构特征不同的乙酰胆碱酯酶抑制剂（AChEIs），利用CATALYST系统构建了乙酰胆碱酯酶抑制剂的药效团模型。确定了具有三个疏水单元、一个环状芳香单元和一个氢键受体单元的最佳药效团模型（权重=3.29，均方根偏差=0.53，总成本-空成本=62.75，相关性=0.93，构型=19.05）。该药效团模型将作用于乙酰胆碱酯酶的双活性位点，能够预测用于阿尔茨海默病（AD）临床治疗的已知乙酰胆碱酯酶抑制剂的活性，并可进一步用于通过虚拟筛选识别具有更高治疗阿尔茨海默病（AD）活性的结构多样的化合物。
