摘要
背景:阿尔茨海默病 (AD) 涉及不可逆和进行性神经变性,具有多因素病理生理学,包括胆碱能缺陷、淀粉样斑块、神经原纤维缠结、氧化应激和神经变性。尽管疾病严重,但治疗手段有限,这引起了研究人员寻找可以作用于这些标志物的物质的兴趣。 目的:在这篇综述中,我们强调了一些相关的观点,例如查耳酮作用于与阿尔茨海默病病理生理学相关的不同靶点的能力;胆碱酯酶、淀粉样肽、β-分泌酶和其他生物标志物。 方法:这篇小型综述涵盖了 2010 年至今有关查耳酮生物活性的文献。除了理论回顾之外,我们还包括使用 SwissADME 软件对物理化学性质的预测。 结果:我们发现大多数查耳酮都经过了胆碱酯酶测试,具有中等至良好的效力,但近年来,与淀粉样蛋白假说目标相关的出版物数量一直在增长。关于理化性质,查耳酮具有良好的特性,但水溶性较差。 结论:这些分子最重要的特征是这里提到的许多例子都作用于多个目标,将它们表征为多目标化合物。关于预测的特性,溶解度是最成问题的一个;然而,这些结构可以结合官能团,从而在不干扰生物活性的情况下规避这个溶解性问题。
关键词: 查耳酮、阿尔茨海默病、胆碱酯酶、淀粉样蛋白、BACE-1、理化特性。
Current Medicinal Chemistry
Title:Chalcones Acting as Inhibitors of Cholinesterases, β-Secretase and β- Amyloid Aggregation and other Targets for Alzheimer’s Disease: A Critical Review
Volume: 28 Issue: 21
关键词: 查耳酮、阿尔茨海默病、胆碱酯酶、淀粉样蛋白、BACE-1、理化特性。
摘要:
Background: Alzheimer's disease (AD) involves an irreversible and progressive neurodegeneration, with multifactorial pathophysiology, including the cholinergic deficit, amyloid plaques, neurofibrillary tangles, oxidative stress, and neurodegeneration. Despite the severity of the disease, the therapeutic arsenal is limited, arousing the interest of researchers to search for substances that can act on these markers.
Objective: In this review, we highlight some relevant points, such as the ability of chalcones to act on different targets related to the pathophysiology of Alzheimer's disease; cholinesterases, amyloid peptide, beta-secretase and other biomarkers.
Method: This mini-review covered the literature concerning chalcones bioactivity from 2010 until now. In addition to the theoretical review, we included the prediction of physicochemical properties using SwissADME software.
Results: We found that the majority of the chalcones have been tested against cholinesterases, with moderate to good potencies, but in recent years, the number of publications related to targets of the amyloid hypothesis has been growing. Regarding the physicochemical properties, chalcones have a good profile, except for the water solubility, which is not favorable.
Conclusion: The most important characteristic of these molecules is that many of the examples mentioned here act on more than one target, characterizing them as multi-target compounds. Regarding predicted properties, solubility stands out as the most problematic one; however, these structures can incorporate functional groups that circumvent this problem of solubility without interfering in the biological activity.
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Chalcones Acting as Inhibitors of Cholinesterases, β-Secretase and β- Amyloid Aggregation and other Targets for Alzheimer’s Disease: A Critical Review, Current Medicinal Chemistry 2021; 28 (21) . https://dx.doi.org/10.2174/0929867327666201020151804
DOI https://dx.doi.org/10.2174/0929867327666201020151804 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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