TY - JOUR
T1 - Discovery of new butyrylcholinesterase inhibitors via structure-based virtual screening
AU - Atatreh, Noor
AU - Al Rawashdah, Sara
AU - Al Neyadi, Shaikha S.
AU - Abuhamdah, Sawsan M.
AU - Ghattas, Mohammad A.
N1 - Funding Information:
This work was funded by the Deanship of Scientific Research and Graduate Studies at Al Ain University of Science and Technology, Al Ain, UAE.
Funding Information:
This work was funded by the Deanship of Scientific Research and Graduate Studies at Al Ain University of Science and Technology, Al Ain, UAE. We are thankful for National Cancer Institute (NCI), USA for freely providing hit compounds for experimental validation. We also thank United Arab Emirate University for conducting the NMR analysis for our compounds.
Publisher Copyright:
© 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Butyrylcholinesterase inhibitors
KW - Ellman’s method
KW - docking
KW - pharmacophore
KW - virtual screening
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U2 - 10.1080/14756366.2019.1644329
DO - 10.1080/14756366.2019.1644329
M3 - Article
C2 - 31347933
AN - SCOPUS:85069629151
SN - 1475-6366
VL - 34
SP - 1373
EP - 1379
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
JF - Journal of Enzyme Inhibition and Medicinal Chemistry
IS - 1
ER -