基于他克林和多奈哌齐的多靶向药物设计及其抗阿尔茨海默病活性研究进展

Progress of Multi-Target Directed Drugs Based on Tacrine and Donepezil in Alzheimer's Disease

阿尔茨海默病(Alzheimer's disease,AD)是一种起病隐匿的进行性发展的神经系统退行性疾病。AD病因复杂,目前尚无有效的治疗方法。鉴于AD复杂的网络病理特征,能够同时作用于多个靶点的单一小分子化合物,即多靶向配体设计(multitarget-directed ligands,MTDLs)被认为是目前有效的治疗策略,其能与多个生物靶点上同时发挥作用,将大大有助于改善AD症状。笔者就近年来基于胆碱酯酶药效团、抗氧化、金属离子络合与神经保护剂等药效团的MTDLs新型候选药物进行了综述。

Alzheimer′s disease (AD) is a progressive multifactorial neurodegenerative disorder in elder people. Currently, the pathogenesis of AD is unclear, and it is presently incurable. In view of the complex network pathological features of AD, a single small molecule compound that can act simultaneously with multiple targets, called multi-target directed ligands (MTDLs), is considered to be an effective therapeutic strategy at present. Here, we review highlights recent MTDLs approach based cholinesterase inhibitors, antioxidant, metal chelator and neuroprotectant in the novel drug candidate prototypes for the treatment of AD.