Design, synthesis and evaluation of novel 4-dimethylamine flavonoid derivatives as potential multi-functional anti-Alzheimer agents

被引：63

作者：

Luo, Wen ^{[1
]}

Su, Ya-Bin ^{[1
,2
]}

Hong, Chen ^{[1
]}

Tian, Run-Guo ^{[1
]}

Su, Lei-Peng ^{[1
]}

Wang, Yue-Qiao ^{[1
]}

Li, Yang ^{[1
]}

Yue, Jun-Jie ^{[2
]}

Wang, Chao-Jie ^{[1
]}

机构：

[1] Henan Univ, Key Lab Nat Med & Immuno Engn, Kaifeng 475004, Peoples R China

[2] Acad Mil Med Sci, Inst Biotechnol, Beijing 100071, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 23期

关键词：

Flavonoid derivatives; Anti-Alzheimer agent; Cholinesterase; Self-induced A beta aggregation; Antioxidation; DISEASE-MODIFYING THERAPIES; ACETYLCHOLINESTERASE INHIBITORS; OXIDATIVE STRESS; AGGREGATION; PEPTIDE; PLAQUES; HYBRIDS; TARGET; PROBES;

D O I：

10.1016/j.bmc.2013.09.061

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

A series of 4-dimethylamine flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential multi-functional anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity at the micromolar range (IC50, 1.83-33.20 mu M for AChE and 0.82-11.45 mu M for BChE). A Lineweaver-Burk plot indicated a mixed-type inhibition for compound 5j with AChE, and molecular modeling study showed that 5j targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, the derivatives showed potent self-induced A beta aggregation inhibitory activity at 20 mu M with percentage from 25% to 48%. In addition, some compounds (5j-5q) showed potent oxygen radical absorbance capacity (ORAC) ranging from 1.5- to 2.6-fold of the Trolox value. These compounds should be further investigated as multi-potent agents for the treatment of Alzheimer's disease. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：7275 / 7282

页数：8

共 32 条

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