• Liyingzi Huang, Yunfeng Luo, Zhijun Pu, Xianghui Kong, Xiang Fu, Huanhuan Xing, Shenqi Wei, Wei Chen, and Huang Tang.
• Affiliated Hospital of Guilin Medicine University, Guilin, Guangxi, China.
• Neurochem. Int. 2017 Sep 1; 108: 157-168.

AbstractAlzheimer's disease (AD) is a multifactorial neurodegenerative disease and a growing health problem worldwide. Because the drugs currently used to treat AD have certain drawbacks such as single targeting, there is a need to develop novel multi-target compounds, among which oxoisoaporphine alkaloid derivatives are promising candidates. In this study, the possible anti-AD activities of 14 novel oxoisoaporphine alkaloid derivatives that we synthesized were screened and evaluated. We found that, in the 14 novel derivatives, compound 8-1 significantly reduced Aβ1-42 secretion in SH-SY5Y cells overexpressing the Swedish mutant form of human β-amyloid precursor protein (APPsw). Next, we found that compound 8-1 could down-regulate the expression level of β-amyloid precursor protein (APP) in APPsw cells. Moreover, compound 8-1 significantly delayed paralysis in the Aβ1-42-transgenic Caenorhabditis elegans strain GMC101, which could be explained by the fact that compound 8-1 down-regulated acetylcholinesterase activity, protected against H2O2-induced acute oxidative stress and paraquat-induced chronic oxidative stress, and enhanced autophagy activity. Taken together, our data suggest that compound 8-1 could attenuate the onset and development of AD.Copyright © 2017. Published by Elsevier Ltd.

43 keywords...

hide…