Dong-Qing Wei
Shanghai Jiaotong University, China
Posters & Accepted Abstracts: Med chem
Based on structure of membrane protein targets acquired by bioinformatics tools and database of molecules extracted from the Traditional Chinese medicines, various cheminformatics procedures were performed to screen for potential active compounds. Many promising molecules were obtained, for example, agaritine and wgx-50 was singled out through similarity search, molecular docking and molecular dynamics simulations. In vivo, the pharmacological kinetics profiles of wgx-50 were obtained to evaluate the effect of wgx-50 on cognition ability of scopolamine induced acute memory damage mice and Amyloid Precursor Protein transgenic (APP-Tg) mice by Morris water maze testing (MWM) and the �²-amyloid (A�²) oligomerics in the brain of APP-Tg mice by immunohistochemisty. In vitro, the direct effect of wgx-50 on A�² oligomerics was observed by the atomic force microscope; the neurocyte protection by Western blot and cell apoptosis assay; and measured intracellular calcium current ([Ca2+]i) by Laser confcal microscopy. Experiments in vivo showed that wgx-50 could penetrate the blood brain barrier and improve the cognition ability and decrease the A�² oligomeric accumulation on cerebral cortex. Results in vitro displayed that wgx-50 could disassemble the A�² oligomerics, inhibit A�²-induced neurocyte apoptosis as well as apoptotic gene expression, and relieve neuron calcium intoxication. These results strongly suggest that wgx-50 possess biologic functions against AD. Discoveries were also made in its potential role in anti-aging.
Email: dqwei@sjtu.edu.cn
Medicinal Chemistry received 5231 citations as per Google Scholar report
