3D-QSAR studies of azaoxoisoaporphine, oxoaporphine, and oxoisoaporphine derivatives as anti-AChE and anti-AD agents by the CoMFA method

作者：Li, Yan-Ping; Weng, Xiang; Ning, Fang-Xian; Ou, Jie-Bin; Hou, Jin-Qiang; Luo, Hai-Bin^*; Li, Ding; Huang, Zhi-Shu; Huang, Shi-Liang; Gu, Lian-Quan

来源：Journal of Molecular Graphics and Modelling, 2013, 41: 61-67.

DOI：10.1016/j.jmgm.2013.02.003

• Azaoxoisoaporphine derivatives
• Alzheimer's disease
• AChE inhibitors
• A beta aggregation
• 3D-QASR
• CoMFA

In the present study, a series of novel azaoxoisoaporphine derivatives were reported and their inhibitory activities toward acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and A beta aggregation were evaluated. The new compounds remained high inhibitory potency on A beta aggregation, with inhibitory activity from 29.42% to 89.63% at a concentration of 10 mu M, but had no action on AChE or BuChE, which was very different from our previously reported oxoaporphine and oxoisoaporphine derivatives. By 3D-QSAR studies, we constructed a reliable CoMFA model (q(2) = 0.856 and r(2) = 0.986) based on the inhibitory activities toward AChE and discovered key information on structure and anti-AChE activities among the azaoxoisoaporphine, oxoaporphine, and oxoisoaporphine derivatives. The model was further confirmed by the test-set validation (q(2) = 0.873, r(2) = 0.937, and slope k = 0.902) and Y-randomization examination. The statistically significant and physically meaningful 3D-QSAR/CoMFA model provided better insight into understanding the inhibitory behaviors of those chemicals, which may provide useful information for the rational molecular design of azaoxoisoaporphine derivatives anti-AChE and anti-AD agents.

• 出版日期2013-4
• 单位中山大学