title: Quantitative structure-activity relationship (QSAR) of tacrine derivatives against acetylcholinesterase (AChE) activity using variable selections.
abstract: A diverse approach to the quantitative structure-activity relationship (QSAR) of tacrine derivatives against acetylcholinesterase (AChE) activity was studied using variable selections of stepwise multiple linear regression (MLR), genetic algorithm (GA)-MLR, and simulated annealing (SA)-MLR. AChE activity (logRA) of tacrine derivatives was expressed with acceptable explanation (95.5-95.9%) and good predictive power (94.5-95.2%), respectively, in the models. The best equation was obtained from simulated annealing (SA) MLR with greater explanatory capability and better prediction, with a smaller standard error than other methods. The resulting models with the given descriptors illustrate the significant roles of hydrophobic and electrostatic interaction on increasing AChE activity, but hydrophilic and topological feature of molecules were shown to decrease AChE activity.
authors.affiliation: Department of Chemistry, Yonsei University, Seoul 120-749, Republic of Korea. mjung@yonsei.ac.kr
authors.forename: Mankil
authors.initials: M
authors.lastname: Jung
authors.forename: Jungae
authors.initials: J
authors.lastname: Tak
authors.forename: Yongnam
authors.initials: Y
authors.lastname: Lee
authors.forename: Youngae
authors.initials: Y
authors.lastname: Jung
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000465:Algorithms; D001185:Artificial Intelligence; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D016014:Linear Models; D008968:Molecular Conformation; D009010:Monte Carlo Method; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D013619:Tacrine; D000110:Acetylcholinesterase