3D-QSAR analysis of a new type of acetylcholinesterase inhibitors.
Acetylcholinesterase (AChE) inhibitors are an important class of medicinal agents used for the treatment of Alzheimer's disease. A screening model of AChE inhibitor was used to evaluate the inhibition of a series of phenyl pentenone derivatives. The assay result showed that some compounds displayed higher inhibitory effects. In order to study the relationship between the bioactivities and the structures, 26 compounds with phenyl pentenone scaffold were analyzed. A 3D-QSAR model was constructed using the method of comparative molecular field analysis (CoMFA). The results of cross-validated R(2)cv=0.629, non-cross-validated R(2)=0.972, SE=0.331, and F=72.41 indicate that the 3D-model possesses an ability to predict the activities of new inhibitors, and the CoMFA model would be useful for the future design of new AChE inhibitors.
Liu
AiLin
A
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Guang
HongMei
H
Zhu
LiYa
L
Du
GuanHua
G
Lee
Simon M Y
SM
Wang
YiTao
Y
D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D010422:Pentanones / Q000737:chemistry / Q000494:pharmacology; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology; D011237:Predictive Value of Tests; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity
D002800:Cholinesterase Inhibitors; D010422:Pentanones; D010636:Phenols; D000110:Acetylcholinesterase