Department of Biochemistry, Institute of Chemical Sciences, Faculty of Science, P. J. Šafárik University in Košice, Moyzesova 11, 040 01, Kosice, Slovak Republic.
Department of Organic Chemistry, Institute of Chemical Sciences, Faculty of Science, P. J. Šafárik University in Košice, Moyzesova 11, 040 01, Kosice, Slovak Republic.
CNS Drugs. 2024 Jul;38(7):507-532. doi: 10.1007/s40263-024-01093-0. Epub 2024 Jun 3.
Numerous physiological processes happening in the human body, including cerebral development and function, require the participation of biometal ions such as iron, copper, and zinc. Their dyshomeostasis may, however, contribute to the onset of Alzheimer's disease (AD) and potentially other neurodegenerative diseases. Chelation of biometal ions is therefore a therapeutic strategy against AD. This review provides a survey of natural and synthetic chelating agents that are or could potentially be used to target the metal hypothesis of AD. Since metal dyshomeostasis is not the only pathological aspect of AD, and the nature of this disorder is very complex and multifactiorial, the most efficient therapeutics should target as many neurotoxic factors as possible. Various coumarin derivatives match this description and apart from being able to chelate metal ions, they exhibit the capacity to inhibit cholinesterases (ChEs) and monoamine oxidase B (MAO-B) while also possessing antioxidant, anti-inflammatory, and numerous other beneficial effects. Compounds based on the coumarin scaffold therefore represent a desirable class of anti-AD therapeutics.
人体中有许多生理过程，包括大脑发育和功能，都需要生物金属离子（如铁、铜和锌）的参与。然而，它们的动态平衡失调可能导致阿尔茨海默病（AD）的发生，并可能导致其他神经退行性疾病。因此，螯合生物金属离子是一种针对 AD 的治疗策略。本综述提供了对天然和合成螯合剂的调查，这些螯合剂或有可能被用于针对 AD 的金属假说。由于金属动态平衡失调不是 AD 的唯一病理方面，而且这种疾病的性质非常复杂和多因素，因此最有效的治疗方法应该针对尽可能多的神经毒性因素。各种香豆素衍生物符合这一描述，除了能够螯合金属离子外，它们还具有抑制胆碱酯酶（ChE）和单胺氧化酶 B（MAO-B）的能力，同时还具有抗氧化、抗炎和许多其他有益作用。因此，基于香豆素支架的化合物代表了一类有前途的抗 AD 治疗药物。
