化学
神经保护
体外
IC50型
阿切
SH-SY5Y型
抑制性突触后电位
药理学
生物化学
铅化合物
淀粉样蛋白(真菌学)
乙酰胆碱酯酶
类黄酮
酶
神经母细胞瘤
抗氧化剂
神经科学
细胞培养
生物
无机化学
遗传学
作者
Shao-Chun Shi,Huibin Wang,Jian Wang,Yvxi Wang,Xiao-Bian Xue,Zi-Lin Hou,Guo-Dong Yao,Xiao‐Xiao Huang,Hongwei Zhao,Qingbo Liu,Shao‐Jiang Song
标识
DOI:10.1016/j.bioorg.2020.103917
摘要
7-O-galloyltricetiflavan (GTF), a natural flavonoid, is known to exert anti-oxidation and neuroprotective activity, which are related to the prevention of Alzheimer’s disease (AD). In this study, three series of GTF hybrids have been designed, synthesized and evaluated as multifunctional agents for treatment AD. The biological assays indicated that most of them showed strong inhibitory effect on self-induced β-amyloid (Aβ) aggregation, and a significant ability to inhibit ChEs. Among them, compound A15 exhibited best inhibition of Aβ aggregation (78.81% at 20 μM), potent AChE inhibitory potencies (IC50, 0.56 μM), and compound C4 presented the highest ability to inhibit BuChE (IC50, 5.77 μM). Furthermore, kinetic, molecular modeling and molecular dynamics studies revealed that A15 and C4 could interact with the catalytic active site of AChE and BuChE, respectively. In addition, compounds A15 and C4 could cross the blood–brain barrier in vitro. More importantly, A15 and C4 also showed excellent neuroprotective activities against H2O2-induced human neuroblastoma SH-SY5Y cells damage and nearly no toxicity on SH-SY5Y cells. All of these outstanding in vitro results indicated A15 and C4 as the leading structure worthy of further investigation.
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