Department of Medicinal Chemistry, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, PR China.
Bioorg Med Chem. 2019 Mar 15;27(6):991-1001. doi: 10.1016/j.bmc.2019.01.040. Epub 2019 Feb 1.
A series of 4'-OH flurbiprofen Mannich base derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. The biological screening results indicated that most of these derivatives exhibited good multifunctional activities. Among them, compound 8n demonstrated the best inhibitory effects on self-induced Aβ aggregation (65.03% at 25.0 μM). Moreover, this representative compound also exhibited good antioxidant activity, biometal chelating ability and anti-neuroinflammatory activity in vitro. Furthermore, compound 8n displayed appropriate blood-brain barrier permeability. These multifunctional properties highlight compound 8n as promising candidate for further development of multi-functional drugs against AD.
设计、合成并评价了一系列 4'-OH 氟比洛芬 Mannich 碱衍生物，作为治疗阿尔茨海默病的潜在多功能药物。生物筛选结果表明，这些衍生物大多数表现出良好的多功能活性。其中，化合物 8n 对自诱导 Aβ 聚集表现出最好的抑制作用（在 25.0µM 时为 65.03%）。此外，该代表性化合物还表现出良好的体外抗氧化活性、生物金属螯合能力和抗神经炎症活性。此外，化合物 8n 显示出适当的血脑屏障通透性。这些多功能特性突出了化合物 8n 作为进一步开发针对 AD 的多功能药物的有前途的候选物。
