Discovery of new acetylcholinesterase inhibitors with small core structures through shape-based virtual screening

Authors: Chen Y, Liu Z, Fu T, Li W, Xu X, Sun H
Publication: Bioorg Med Chem Lett.
Software: ADMET Predictor®


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.