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Discovery and evaluation of novel butyrylcholinesterase inhibitors for the treatment of Alzheimer's disease (BChI for AD therapy)
Start date: 27 Sep 2008, End date: 26 Sep 2010 PROJECT  FINISHED 

Alzheimer's disease (AD) is the most common neurodegenerative disorder and is incurable. A drug candidate specifically inhibiting butyrylcholinesterase (BChE) activity will lead to improved clinical outcome in the treatment of AD. The fellow Qiong Shen (QS) has extensive experience, knowledge and technical skills in research into AD. Previously she developed chemistry and successfully synthesised a series of novel coumarine derivatives. She carried out biological assessment and demonstrated potent anti-chlolineric activity of the compounds. She developed structure-activity relationships and generated several inhibitor drug candidates. In this project, QS will bring her expertise of natural product chemistry and an understanding of the disease to the UoN, where the research in neurodegenerative diseases has been hampered by lack of the expertise and appropriate project. She will start this project by adapting the pharmacophore model she developed previously to generate a class of novel BChE inhibitors. She will prepare a library of heterocyclic compounds possessing novel and diverse structures inspired by natural medicinal molecules. The inhibitory activity against AChE and BChE will be assayed. The drug-likeness of the lead compounds will be further assessed in in vitro ADME/Tox assays. The success of this project will place the UoN at the forefront of research into CNS diseases. In addition, the involvement of QS will allow the UoN/EU to access to wealth of natural medicinal chemistry and compound collections held by her research associates at Sun Yat-Sen University and Guangdong Pharmaceutical University in China. The extensive proprietary and historical compound collections will form a major resource for future collaboration and new drug discovery project starting points. The proposed project is an ideal seeding programme providing stimulation and impetus for more extensive collaboration between the EU and China.
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