Department of Neurology, Tangshan Workers Hospital, Tangshan, Hebei, 063000, China.
Innoscience Research Sdn Bhd, Jalan USJ 25/1, 47650 Subang Jaya, Selangor, Malaysia.
Curr Pharm Des. 2020;26(37):4808-4814. doi: 10.2174/1381612826666200407161842.
Alzheimer's disease (AD) is the most well-known reason for disability in persons aged greater than 65 years worldwide. AD influences the part of the brain that controls cognitive and non-cognitive functions.
The study focuses on the screening of natural compounds for the inhibition of AChE and BuChE using a computational methodology.
We performed a docking-based virtual screening utilizing the 3D structure of AChE and BuChE to search for potential inhibitors for AD. In this work, a screened inhibitor Ajmalicine similarity search was carried out against a natural products database (Super Natural II). Lipinski rule of five was carried out and docking studies were performed between ligands and enzyme using 'Autodock4.2'.
Two phytochemical compounds SN00288228 and SN00226692 were predicted for the inhibition of AChE and BuChE, respectively. The docking results revealed Ajmalicine, a prominent natural alkaloid, showing promising inhibitory potential against AChE and BuChE with the binding energy of -9.02 and -8.89 kcal/mole, respectively. However, SN00288228- AChE, and SN00226692-BuChE were found to have binding energy -9.88 and -9.54 kcal/mole, respectively. These selected phytochemical compounds showed better interactions in comparison to Ajmalicine with the target molecule.
The current study verifies that SN00288228 and SN00226692 are more capable inhibitors of human AChE and BuChE as compared to Ajmalicine with reference to ΔG values.
阿尔茨海默病（AD）是全球 65 岁以上人群残疾的最常见原因。AD 影响控制认知和非认知功能的大脑部分。
本研究采用计算方法，专注于筛选抑制乙酰胆碱酯酶和丁酰胆碱酯酶的天然化合物。
我们利用 AChE 和 BuChE 的 3D 结构进行基于对接的虚拟筛选，以寻找 AD 的潜在抑制剂。在这项工作中，对天然产物数据库（Super Natural II）进行了阿马碱相似性搜索筛选。进行了 Lipinski 五规则筛选，并使用“Autodock4.2”在配体和酶之间进行对接研究。
预测了两种植物化学化合物 SN00288228 和 SN00226692 分别抑制 AChE 和 BuChE。对接结果表明，阿马碱是一种重要的天然生物碱，对 AChE 和 BuChE 表现出有希望的抑制潜力，结合能分别为-9.02 和-8.89 kcal/mol。然而，SN00288228-AChE 和 SN00226692-BuChE 的结合能分别为-9.88 和-9.54 kcal/mol。与靶分子相比，这些选定的植物化学化合物表现出更好的相互作用。
与阿马碱相比，当前的研究通过ΔG 值验证了 SN00288228 和 SN00226692 是更有效的人乙酰胆碱酯酶和丁酰胆碱酯酶抑制剂。
