PDF(Pubmed)
Abstract：
Alzheimer\'s disease (AD) is the most prevalent neurodegenerative disease that affects people aged 60 years and above. Yet, the discovery of potent therapeutic agents against this disease has no utmost progress and a number of drug candidates could not make it out of the clinical trials at varied stages. At the same time, the currently available anti-cholinesterase (AChE) and monoamine oxidase-B (MAO-B) for the treatment of AD can only improve the clinical symptoms while the recently approved immunotherapy agent \"remains questionable. Thus, the need for novel therapeutic agents with the potential to treat the aetiology of the disease. Herein, this study sought to examine the potential of a number of bioactive compounds derived from Vitis vinifera as a promising agent against AChE and MAO-B. Using a computational approach via molecular docking 23 bioactive agents were screened against AChE and MAO-B, and the compounds with a binding score below that of the standard ligand were further subjected to drug-likeness and pharmacokinetic screening. Eight and thirteen of the studied agents optimally saturated the active pocket of the AChE and MAO-B respectively, forming principal interactions with a number of amino acids at the active pocket of the targets and among these compounds only rutin failed the drug-likeness test by violating four parameters while all showed moderate pharmacokinetics features. A number of Vitis vinifera-derived bioactive compounds show excellent inhibitory potential against AChE and MAO-B, and moderate pharmacokinetic features when compared to the reference ligand (tacrine). These compounds are therefore proposed as novel AChE and MAO-B inhibitors for the treatment of AD and wet-lab analysis is necessary to affirm their potency.
摘要：
阿尔茨海默病(Alzheimer’sdisease,AD)是影响60岁及以上人群的最常见的神经退行性疾病。然而，针对这种疾病的有效治疗药物的发现并没有取得最大进展，许多候选药物无法在不同阶段退出临床试验。同时,目前可用的抗胆碱酯酶(AChE)和单胺氧化酶-B(MAO-B)治疗AD只能改善临床症状,而最近批准的免疫治疗药物仍有疑问.因此，需要具有治疗该病病因潜力的新型治疗剂。在这里，这项研究试图研究许多来自葡萄的生物活性化合物作为抗AChE和MAO-B的有前途的药物的潜力。使用通过分子对接的计算方法，针对AChE和MAO-B筛选了23种生物活性剂，和结合评分低于标准配体的化合物进一步进行药物相似度和药代动力学筛选。所研究的试剂中的八种和十三种分别最佳地饱和了AChE和MAO-B的活性口袋，在目标的活性口袋中与许多氨基酸形成主要相互作用，在这些化合物中，只有芦丁通过违反四个参数而未能通过药物相似度测试，而全部显示出中等的药代动力学特征。许多葡萄衍生的生物活性化合物对AChE和MAO-B显示出优异的抑制潜力，与参考配体（他克林）相比，具有中等的药代动力学特征。因此,这些化合物被提出作为用于治疗AD的新型AChE和MAO-B抑制剂,并且湿实验室分析对于确认它们的效力是必要的。
