Discovery of new butyrylcholinesterase inhibitors via structure-based virtual screening

被引：34

作者：

Atatreh, Noor ^{[1
]}

Al Rawashdah, Sara ^{[1
]}

Al Neyadi, Shaikha S. ^{[2
]}

Abuhamdah, Sawsan M. ^{[1
,3
]}

Ghattas, Mohammad A. ^{[1
]}

机构：

[1] Al Ain Univ Sci & Technol, Coll Pharm, POB 112612, Abu Dhabi, U Arab Emirates

[2] UAE Univ, Coll Sci, Dept Chem, Al Ain, U Arab Emirates

[3] Univ Jordan, Fac Pharm, Dept Biopharmaceut & Clin Pharm, Amman, Jordan

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2019年 / 34卷 / 01期

关键词：

Butyrylcholinesterase inhibitors; Alzheimer's disease; Ellman's method; virtual screening; docking; pharmacophore; ALZHEIMERS-DISEASE; CARBONIC-ANHYDRASE; ACETYLCHOLINESTERASE; IDENTIFICATION; BIOLOGY; PROTEIN;

D O I：

10.1080/14756366.2019.1644329

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 mu M. Hits obtained from this work can act as a starting point for future SAR studies to discover new BChE inhibitors as anti-Alzheimer agents.

引用

页码：1373 / 1379

页数：7

共 42 条

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