期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 21, 期 23, 页码 7275-7282出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2013.09.061
关键词
Flavonoid derivatives; Anti-Alzheimer agent; Cholinesterase; Self-induced A beta aggregation; Antioxidation
资金
- Natural Science Foundation of China [21172053, 21302041]
- Postdoctoral Science Foundation of China [2012M521391]
- Postdoctoral Science Foundation of Henan Province [BH2011043]
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.
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