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Discovery of new butyrylcholinesterase inhibitors via structure-based virtual screening

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journal contribution
posted on 26.07.2019, 12:47 by Noor Atatreh, Sara Al Rawashdah, Shaikha S. Al Neyadi, Sawsan M. Abuhamdah, Mohammad A. Ghattas

Butyrylcholinesterase (BChE) plays an important role in the progression of the Alzheimer’s disease. In this study, we used a structure-based virtual screening (VS) approach to discover new BChE inhibitors. A ligand database was filtered and docked to the BChE protein using Glide program. The outcome from VS was filtered and the top ranked hits were thoroughly examined for their fitting into the protein active site. Consequently, the best 38 hits were selected for in vitro testing using Ellman’s method, and six of which showed inhibition activity for BChE. Interestingly, the most potent hit (Compound 4) exhibited inhibitory activity against the BChE enzyme in the low micromolar level with an IC50 value of 8.3 µM. Hits obtained from this work can act as a starting point for future SAR studies to discover new BChE inhibitors as anti-Alzheimer agents.


This work was funded by the Deanship of Scientific Research and Graduate Studies at Al Ain University of Science and Technology, Al Ain, UAE.