Laboratory of Applied Biochemistry, Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, University Mentouri Brothers Constantine 1, Algeria.
Chemistry, Modeling and Imaging for Biology (CMIB), Institut Curie, PSL Research University, CNRS UMR 9187 - INSERM U1196, Paris-Saclay University, F-91405, Orsay, France.
Mol Inform. 2019 May;38(5):e1800118. doi: 10.1002/minf.201800118. Epub 2019 Feb 6.
Acetylcholinesterase (AChE) is currently the most favorable target for the symptomatic treatment and reduction of Alzheimer's disease (AD). In order to identify new potent inhibitors of this enzyme, we describe herein a new structure-based virtual screening (SBVS) using the Institut Curie-CNRS chemical library (ICCL), which contained at the screening date 14307 compounds. The strategy undertaken in this work consisted of the use of several docking programs in SBVS calculations followed by the application of a consensus method (vSDC) and a scrupulous visual analysis. It allowed us to obtain a high degree of success, with a yield of almost 86 %, since 12 hits were identified among only 14 molecules tested in vitro. Still more remarkably, 6 of these hits were more active than galantamine, the reference inhibitor. These hits were predicted to have good ADMET properties. The two most promising compounds can serve as leads for AD treatment.
乙酰胆碱酯酶（AChE）是目前用于治疗症状和减轻阿尔茨海默病（AD）的最理想靶点。为了鉴定这种酶的新型有效抑制剂，我们在此描述了一种新的基于结构的虚拟筛选（SBVS）方法，使用了居里研究所-法国国家科学研究中心化学库（ICCL），该库在筛选时包含了 14307 种化合物。这项工作中采用的策略包括在 SBVS 计算中使用多个对接程序，然后应用共识方法（vSDC）和严格的视觉分析。该方法使我们获得了很高的成功率，几乎达到了 86%，因为在体外仅测试了 14 种分子，就鉴定出了 12 个命中物。更值得注意的是，其中 6 个命中物比加兰他敏（参考抑制剂）更有效。这些命中物被预测具有良好的 ADMET 特性。这两种最有前途的化合物可以作为治疗 AD 的先导化合物。
