Conformational Analysis and Docking Study of Potent Acetylcholinesterase Inhibitors Having a Benzylamine Moiety

Chem-Bio Informatics Journal

Tsugio Kaneko²  Narihiro Toda¹  Shuichi Miyamoto¹  Yoriko Iwata¹  Keiko Tago¹  Hiroshi Kogen¹ 

[1] Exploratory Chemistry Research Laboratories, Sankyo Co., Ltd.;Neuroscience and Immunology Research Laboratories, Sankyo Co., Ltd.

关键词: conformational analysis;    配座解析;    docking study;    ドッキングスタディ;    molecular mechanics;    分子力学法;    molecular dynamics;    分子動力学法;    acethylcholinesterase inhibitor;    アセチルコリンエステラーゼ阻害剤;    structure-activity relationship;    構�?�活性相関;    nitrophenoxyalkylbenzylamine;    ニトロフェノキシアルキルベンジルアミン;    stereoisomer;    光学活�?�体;   

DOI  :  10.1273/cbij.3.46

学科分类：生物化学/生物物理

来源: Chem-Bio Informatics Society

【 摘 要 】

References(29)Cited-By(1)A conformational analysis and docking study of nitrophenoxyalkylbenzylamine derivatives with inhibitory activities against acethylcholinesterase was carried out in an attempt to analyze their structure-activity relationships based on the enzyme-inhibitor interaction. First, stable conformers of the inhibitors alone were obtained from the conformational analysis by molecular dynamics. Next, a docking study of the inhibitors into the ligand binding site was performed. Among the resulting stable complex structures, it was found that in the case of the two stereoisomers with a 7-membered ring, the more active one of the two formed a much more stable complex structure. On the other hand, complex structures with comparable energies were obtained for both stereoisomers that had no 7-membered ring and showed similar inhibitory activities. Lastly, structural features of the complex models of a series of inhibitors with side chains of different lengths were evaluated and corresponded well to their inhibitory activities.

【 授权许可】

Unknown