Construction of the pharmacophore model of acetylcholinesterase inhibitor.
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.
Zhu
Yong
Y
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Tong
Xin-Yue
XY
Zhao
Yue
Y
Chen
Hui
H
Jiang
Feng-Chao
FC
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000544:Alzheimer Disease / Q000201:enzymology / Q000517:prevention & control; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000145:classification / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase