设计、合成及评估喹啉-氨基甲酸酯衍生物作为治疗阿尔茨海默病的多功能药物。

Design, synthesis and evaluation of quinoline--carbamate derivatives as multifunctional agents for the treatment of Alzheimer's disease.

机构信息

Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology, College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, Inner Mongolia, China.

College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang, Henan, China.

出版信息

J Enzyme Inhib Med Chem. 2023 Dec;38(1):2169682. doi: 10.1080/14756366.2023.2169682.

A series of novel quinoline--carbamate derivatives was rationally designed for treating Alzheimer's disease (AD) by multi-target-directed ligands (MTDLs) strategy. The target compounds were synthesised and evaluated by AChE/BuChE inhibition and anti-inflammatory property. The in vitro activities showed that compound was a reversible dual AChE/eqBuChE inhibitor with IC values of 1.3 µM and 0.81 µM, respectively. Moreover, compound displayed good anti-inflammatory property by decreasing the production of IL-6, IL-1β and NO. In addition, compound presented significant neuroprotective effect on A-induced PC12 cell injury. Furthermore, compound presented good stabilities in artificial gastrointestinal fluids, liver microsomes and plasma. Furthermore, compound could improve AlCl-induced zebrafish AD model by increasing the level of ACh. Therefore, compound was a promising multifunctional agent for the treatment of AD.

我们设计了一系列新型的喹啉-氨基甲酸酯衍生物，通过多靶点导向配体（MTDLs）策略来治疗阿尔茨海默病（AD）。目标化合物通过 AChE/BuChE 抑制和抗炎活性进行了合成和评估。体外活性结果表明，化合物是一种可逆的双重 AChE/eqBuChE 抑制剂，IC 值分别为 1.3µM 和 0.81µM。此外，化合物通过降低 IL-6、IL-1β 和 NO 的产生表现出良好的抗炎活性。此外，化合物对 A 诱导的 PC12 细胞损伤表现出显著的神经保护作用。此外，化合物在人工胃肠液、肝微粒体和血浆中具有良好的稳定性。此外，化合物可以通过增加 ACh 的水平来改善 AlCl 诱导的斑马鱼 AD 模型。因此，化合物是一种有前途的多功能 AD 治疗药物。