Li Yan, Qiang Xiaoming, Luo Li, Li Yuxing, Xiao Ganyuan, Tan Zhenghuai, Deng Yong
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. 2016 May 15;24(10):2342-51. doi: 10.1016/j.bmc.2016.04.012. Epub 2016 Apr 5.
A series of 4-hydroxyl aurone derivatives were designed synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. The results demonstrated that most of the derivatives exhibited good multifunctional properties. Among them, compound 14e displayed good inhibitory activities of self- and Cu(2+)-induced Aβ1-42 aggregation with 99.2% and 84.0% at 25μM, respectively, and high antioxidant activity with a value 1.90-fold of Trolox. In addition, 14e also showed remarkable inhibitory activities of both monoamine oxidase A and B with IC50 values of 0.271μM and 0.393μM, respectively. However the 6-methoxyl aurones 15a-c revealed excellent selectivity toward MAO-B. Furthermore, the representative compounds 14e and 15b displayed good metal-chelating abilities and blood-brain barrier (BBB) permeabilities in vitro.
设计、合成并评估了一系列4-羟基奥洛酮衍生物作为治疗阿尔茨海默病的潜在多功能药物。结果表明，大多数衍生物表现出良好的多功能特性。其中，化合物14e在25μM时对自身诱导和铜（2+）诱导的Aβ1-42聚集分别表现出99.2%和84.0%的良好抑制活性，以及抗氧化活性，其值是Trolox的1.90倍。此外，14e对单胺氧化酶A和B也表现出显著的抑制活性，IC50值分别为0.271μM和0.393μM。然而，6-甲氧基奥洛酮15a-c对MAO-B表现出优异的选择性。此外，代表性化合物14e和15b在体外表现出良好的金属螯合能力和血脑屏障（BBB）通透性。
