Department of Organic Chemistry, Gdansk University of Technology, 11/12 G. Narutowicza Street, 80-233, Gdansk, Poland.
Department of Medical Chemistry, Medical University of Gdansk, Debinki 1 Street, 80-211 Gdansk, Poland.
Curr Neuropharmacol. 2019;17(5):472-490. doi: 10.2174/1570159X16666180412091908.
Tacrine is a potent inhibitor of cholinesterases (acetylcholinesterase and butyrylcholinesterase) that shows limiting clinical application by liver toxicity. In spite of this, analogues of tacrine are considered as a model inhibitor of cholinesterases in the therapy of Alzheimer's disease. The interest in these compounds is mainly related to a high variety of their structure and biological properties. In the present review, we have described the role of cholinergic transmission and treatment strategies in Alzheimer's disease as well as the synthesis and biological activity of several recently developed classes of multifunctional tacrine analogues and hybrids, which consist of a new paradigm to treat Alzheimer's disease. We have also reported potential of these analogues in the treatment of Alzheimer's diseases in various experimental systems.
他克林是一种强效的胆碱酯酶抑制剂（乙酰胆碱酯酶和丁酰胆碱酯酶），但由于其肝毒性而限制了其临床应用。尽管如此，他克林的类似物仍被认为是阿尔茨海默病治疗中胆碱酯酶的模型抑制剂。人们对这些化合物的兴趣主要与它们结构和生物学性质的多样性有关。在本综述中，我们描述了胆碱能传递在阿尔茨海默病中的作用以及治疗策略，以及最近开发的几类多功能他克林类似物和杂合物的合成和生物学活性，这些类似物为治疗阿尔茨海默病提供了一种新的模式。我们还报告了这些类似物在各种实验系统中治疗阿尔茨海默病的潜力。
