Discovery of 4′-OH-flurbiprofen Mannich base derivatives as potential Alzheimer's disease treatment with multiple inhibitory activities

作者：Liu, Hongyan; Qiang, Xiaoming; Song, Qing; Li, Wei; He, Yuxi; Ye, Chanyuan; Tan, Zhenghuai; Deng, Yong^*

来源：Bioorganic & Medicinal Chemistry, 2019, 27(6): 991-1001.

DOI：10.1016/j.bmc.2019.01.040

• Alzheimer's disease
• Flurbiprofen Mannich bases
• Multifunctional agents
• Antioxidant activity
• A beta aggregation inhibitor
• Anti-neuroinflammatory agents

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 A beta(1-42) aggregation (65.03% at 25.0 mu M). 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.

• 出版日期2019-3-15
• 单位四川大学; 四川省中医药科学院