多靶点阿尔茨海默症治疗药物的研究进展

Development of multiple-target anti-Alzheimer′s agents

临床上用于治疗阿尔茨海默症(AD)的药物多属于针对单靶标的化合物,这类化合物可缓解AD症状,但未能从根本上改善疾病状态或终止疾病的进程。基于AD的发生和发展涉及到多个复杂的调控网络和调控因子的共同作用,寻求针对多个靶点的化合物成了AD治疗药物研发的热点和趋势。本文对近几年报道的各类多靶点抗AD药物或化合物进行综述,从其发现、设计思路、生物活性及应用前景等方面进行系统阐述。

Alzheimer＇s disease （AD）, the most common form of dementia, is ascribed to a considerably complex neurodegenerative disorder. Currently, drugs approved for AD treatment are mainly AChE inhibitors and NMDA antagonists, as single-target anti-AD drugs, both of which can only be employed to alleviate the symptoms of AD. Thus, more effective AD treatment is more attractive and becoming one of the hotspots. Because of the complexity and multiple etiologies of AD, multi-target-directed ligand raises as a potentially more effective strategy for AD treatment. This review mainly focused on the discovery, structural optimization, biological activity and potential prospect of a variety of reported multi-target-directed compounds.