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Volume 24
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10.3390/molecules24234217
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Article

Discovery of Selective Butyrylcholinesterase (BChE) Inhibitors through a Combination of Computational Studies and Biological Evaluations

by
You Zhou
1,*,
Xin Lu
2,
Hongyu Yang
2,
Yao Chen
3,
Feng Wang
1,
Jifu Li
1,
Zhiran Tang
4,
Xifei Cheng
1,
Yingbin Yang
4,
Li Xu
1 and
Qingyou Xia
1,*
1
State Key Laboratory of Silkworm Genome Biology, College of Biotechnology, Southwest University, Chongqing 400715, China
2
School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
3
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
4
School of Life Science, Southwest University, Chongqing 400715, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Ludovic Jean
Molecules 2019, 24(23), 4217; https://doi.org/10.3390/molecules24234217
Received: 7 November 2019 / Revised: 14 November 2019 / Accepted: 17 November 2019 / Published: 20 November 2019
(This article belongs to the Special Issue Cholinesterase Inhibitors)
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Abstract

As there are increased levels and activity of butyrylcholiesterase (BChE) in the late stage of Alzheimer’s disease (AD), development of selective BChE inhibitors is of vital importance. In this study, a workflow combining computational technologies and biological assays were implemented to identify selective BChE inhibitors with new chemical scaffolds. In particular, a pharmacophore model served as a 3D search query to screen three compound collections containing 3.0 million compounds. Molecular docking and cluster analysis were performed to increase the efficiency and accuracy of virtual screening. Finally, 15 compounds were retained for biological investigation. Results revealed that compounds 8 and 18 could potently and highly selectively inhibit BChE activities (IC50 values < 10 μM on human BChE, selectivity index BChE > 30). These active compounds with novel scaffolds provided us with a good starting point to further design potent and selective BChE inhibitors, which may be beneficial for the treatment of AD. View Full-Text
Keywords: Alzheimer’s disease; selective butyrylcholiesterase inhibitors; virtual screening; pharmacophore model; acetylcholinesterase; in vitro enzyme assays Alzheimer’s disease; selective butyrylcholiesterase inhibitors; virtual screening; pharmacophore model; acetylcholinesterase; in vitro enzyme assays
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

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MDPI and ACS Style

Zhou, Y.; Lu, X.; Yang, H.; Chen, Y.; Wang, F.; Li, J.; Tang, Z.; Cheng, X.; Yang, Y.; Xu, L.; Xia, Q. Discovery of Selective Butyrylcholinesterase (BChE) Inhibitors through a Combination of Computational Studies and Biological Evaluations. Molecules 2019, 24, 4217. https://doi.org/10.3390/molecules24234217

AMA Style

Zhou Y, Lu X, Yang H, Chen Y, Wang F, Li J, Tang Z, Cheng X, Yang Y, Xu L, Xia Q. Discovery of Selective Butyrylcholinesterase (BChE) Inhibitors through a Combination of Computational Studies and Biological Evaluations. Molecules. 2019; 24(23):4217. https://doi.org/10.3390/molecules24234217

Chicago/Turabian Style

Zhou, You, Xin Lu, Hongyu Yang, Yao Chen, Feng Wang, Jifu Li, Zhiran Tang, Xifei Cheng, Yingbin Yang, Li Xu, and Qingyou Xia. 2019. "Discovery of Selective Butyrylcholinesterase (BChE) Inhibitors through a Combination of Computational Studies and Biological Evaluations" Molecules 24, no. 23: 4217. https://doi.org/10.3390/molecules24234217

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