新型阿魏酸-美金刚喹啉杂合物作为治疗阿尔茨海默病潜在多功能药物的设计、合成与评价
Design, synthesis and evaluation of novel ferulic acid-memoquin hybrids as potential multifunctional agents for the treatment of Alzheimer's disease.
作者信息
Pan Wanli, Hu Ke, Bai Ping, Yu Lintao, Ma Qinge, Li Tao, Zhang Xu, Chen Changzhong, Peng Kelin, Liu Wenmin, Sang Zhipei
机构信息
College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061, China.
Nanyang City Center Hospital, Nanyang 473061, China.
出版信息
Bioorg Med Chem Lett. 2016 May 15;26(10):2539-2543. doi: 10.1016/j.bmcl.2016.03.086. Epub 2016 Mar 25.
A novel series of ferulic acid-memoquin hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The in vitro studies showed that most of the compounds exhibited a significant ability to inhibit acetylcholinesterase (AChE) (IC50 of 3.2-34.7μM) and self-induced β-amyloid (Aβ1-42) aggregation (30.8-39.1%, 25μM), to act as potential antioxidants (ORAC-FL value of 0.9-1.3). In particular, compound 17d had the greatest ability to inhibit AChE (IC50=3.2μM), and Aβ1-42 aggregation (30.8%) was also an excellent antioxidant and neuroprotectant. Moreover, it is capable of disaggregating self-induced Aβ aggregation. Furthermore, 17d could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 17d is a potential multifunctional agent for the treatment of AD.
设计、合成了一系列新型阿魏酸-美金刚喹啉杂合物，并将其作为治疗阿尔茨海默病（AD）的多功能药物进行评估。体外研究表明，大多数化合物表现出显著的抑制乙酰胆碱酯酶（AChE）的能力（IC50为3.2 - 34.7μM）以及抑制自身诱导的β-淀粉样蛋白（Aβ1-42）聚集的能力（在25μM时为30.8 - 39.1%），还具有潜在的抗氧化能力（ORAC-FL值为0.9 - 1.3）。特别地，化合物17d具有最强的抑制AChE的能力（IC50 = 3.2μM），对Aβ1-42聚集的抑制率为30.8%，它还是一种出色的抗氧化剂和神经保护剂。此外，它能够使自身诱导的Aβ聚集解聚。而且，17d在体外能够穿过血脑屏障（BBB）。结果表明化合物17d是一种治疗AD的潜在多功能药物。
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