基于结构的虚拟筛选发现新型丁酰胆碱酯酶抑制剂。
Discovery of new butyrylcholinesterase inhibitors via structure-based virtual screening.
机构信息
a College of Pharmacy, Al Ain University of Science and Technology , Abu Dhabi , UAE.
b Department of Chemistry, College of Science, UAE University , Al-Ain , UAE.
出版信息
J Enzyme Inhib Med Chem. 2019 Dec;34(1):1373-1379. doi: 10.1080/14756366.2019.1644329.
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 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.
丁酰胆碱酯酶（BChE）在阿尔茨海默病的发展中起着重要作用。在这项研究中，我们使用基于结构的虚拟筛选（VS）方法来发现新的 BChE 抑制剂。使用 Glide 程序筛选配体数据库并对接 BChE 蛋白。从 VS 中筛选出的结果，并对排名最高的命中进行了深入检查，以了解它们是否适合蛋白质的活性部位。因此，选择了最好的 38 个命中进行 Ellman 法测试，其中 6 个显示出对 BChE 的抑制活性。有趣的是，最有效的命中（化合物 4）以低微摩尔水平显示出对 BChE 酶的抑制活性，IC50 值为 8.3µM。从这项工作中获得的命中可以作为未来 SAR 研究的起点，以发现新的 BChE 抑制剂作为抗阿尔茨海默病药物。
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