Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan academy of Chinese Medicine Sciences, Chengdu 610041, China.
Bioorg Med Chem. 2018 Mar 1;26(5):1102-1115. doi: 10.1016/j.bmc.2018.01.030. Epub 2018 Feb 2.
A series of 4'-OH-flurbiprofen-chalcone hybrids 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 hybrids exhibited good multifunctional activities. Among them, compounds 7k and 7m demonstrated the best inhibitory effects on self-induced Aβ aggregation (60.0% and 78.2%, respectively) and Cu-induced Aβ aggregation (52.4% and 95.0%, respectively). Moreover, these two representative compounds also exhibited good antioxidant activities, MAO inhibitions, biometal chelating abilities and anti-neuroinflammatory activities in vitro. Furthermore, compound 7m displayed appropriate blood-brain barrier permeability. These multifunctional properties highlight compound 7k and 7m as promising candidates for further development of multi-functional drugs against AD.
一系列 4'-OH-氟比洛芬查耳酮杂合体被设计、合成并评估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，这些杂合体中的大多数表现出良好的多功能活性。其中，化合物 7k 和 7m 对自诱导的 Aβ 聚集显示出最好的抑制作用（分别为 60.0%和 78.2%）和 Cu 诱导的 Aβ 聚集（分别为 52.4%和 95.0%）。此外，这两个代表性化合物还表现出良好的抗氧化活性、MAO 抑制活性、生物金属螯合能力和体外抗神经炎症活性。此外，化合物 7m 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 7k 和 7m 作为进一步开发多功能抗 AD 药物的有前途的候选药物。
