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Discovery of new acetylcholinesterase inhibitors with small core structures through shape-based virtual screening
Yao Chen1, Zong-liang Liu2, Ting-ming Fu1
1School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210038, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, China.
Abstract:
Targeting acetylcholinesterase (AChE) using small molecule inhibitors is considered to be the most successful therapeutic strategy in the treatment of Alzheimer's disease (AD). Herein we present a shape-based virtual screening to identify new cores for the designing of AChE inhibitors. Ten active hits are identified and the most active hit, 5169-0032 and T5369186, showed comparable AChE inhibitory activity to tacrine. Prediction of physicochemical properties and ADME/T risk indicates their potential in druggability and safety. The two compounds provide new core and can serve as a promising fragment to design potent AChE inhibitors.
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