利用有机化合物抑制 BACE1有望成为阿尔茨海默氏症和帕金森氏症的潜在治疗方法

2区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Razieh Amini, Shadi Moradi, Rezvan Najafi, Mehrdokht Mazdeh, Amir Taherkhani
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引用次数: 0

摘要

背景。阿尔茨海默病(AD)和帕金森病(PD)等神经系统疾病表现为认知功能逐渐恶化。解决这些疾病的一个令人鼓舞的策略是抑制前体分解酶 1 (BACE1)。研究目的在目前的研究中,我们采用了虚拟筛选技术,从选定的草药分离物中找出潜在的 BACE1 抑制剂。方法。本研究评估了 79 种黄酮类化合物、蒽醌类化合物 (AQ) 和肉桂酸衍生物的潜在血脑屏障 (BBB) 渗透性。使用 AutoDock 4.0 工具进行了分子对接分析,以确定 BBB 可渗透化合物与 BACE1 活性位点的结合亲和力。还进行了分子动力学(MD)模拟,以评估最有效抑制剂对接姿势的稳定性。在进行 MD 模拟之前和之后,研究了最有效的植物抑制剂与 BACE1 催化位点内残基之间的相互作用。结果显示椪柑素、丹参酮、菊花酚和 N-对香豆酰酪胺是排名最靠前的 BACE1 抑制剂,其抑制常数的计算值在纳摩尔范围内。此外,在 10 ns 模拟期间,还观察到这些配体的对接位置是稳定的。结论研究结果表明,芒柄蜡素、丹参酮、金丝桃醇和N-对香豆酰酪胺可能成为治疗AD和PD的潜在选择,为创造创新的BACE1抑制剂奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
BACE1 Inhibition Utilizing Organic Compounds Holds Promise as a Potential Treatment for Alzheimer’s and Parkinson’s Diseases
Background. Neurological disorders like Alzheimer’s disease (AD) and Parkinson’s disease (PD) manifest through gradually deteriorating cognitive functions. An encouraging strategy for addressing these disorders involves the inhibition of precursor-cleaving enzyme 1 (BACE1). Objectives. In the current research, a virtual screening technique was employed to identify potential BACE1 inhibitors among selected herbal isolates. Methods. This study evaluated 79 flavonoids, anthraquinones (AQs), and cinnamic acid derivatives for their potential blood–brain barrier (BBB) permeability. Using the AutoDock 4.0 tool, molecular docking analysis was conducted to determine the binding affinity of BBB permeable compounds to the BACE1 active site. Molecular dynamics (MD) simulations were performed to assess the stability of the docked poses of the most potent inhibitors. The interactions between the most effective plant-based inhibitors and the residues within the BACE1 catalytic site were examined before and after MD simulations. Results. Ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine were among the highest-ranking BACE1 inhibitors, with inhibition constant values calculated in the nanomolar range. Furthermore, during 10 ns simulations, the docked poses of these ligands were observed to be stable. Conclusion. The findings propose that ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine might serve as potential choices for the treatment of AD and PD, laying the groundwork for the creation of innovative BACE1 inhibitors.
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来源期刊
CiteScore
13.20
自引率
0.00%
发文量
1274
审稿时长
3-8 weeks
期刊介绍: Oxidative Medicine and Cellular Longevity is a unique peer-reviewed, Open Access journal that publishes original research and review articles dealing with the cellular and molecular mechanisms of oxidative stress in the nervous system and related organ systems in relation to aging, immune function, vascular biology, metabolism, cellular survival and cellular longevity. Oxidative stress impacts almost all acute and chronic progressive disorders and on a cellular basis is intimately linked to aging, cardiovascular disease, cancer, immune function, metabolism and neurodegeneration. The journal fills a significant void in today’s scientific literature and serves as an international forum for the scientific community worldwide to translate pioneering “bench to bedside” research into clinical strategies.
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