Design, synthesis, and biological activity evaluation of BACE1 inhibitors with antioxidant activity

被引：8
作者：
Li, He-Min [1 ]
Yu, Shao-Peng [1 ]
Fan, Yuan [1 ]
Zhong, Yue [1 ]
Gu, Ting [1 ]
Wu, Wen-Yu [1 ]
Zhao, Chao [1 ]
Chen, Zhi [1 ]
Chen, Min [1 ]
Li, Nian-Guang [1 ]
Wang, Xiao-Long [1 ]
机构：
[1] Nanjing Univ Chinese Med, Dept Med Chem, Nanjing 210023, Jiangsu, Peoples R China
来源：
DRUG DEVELOPMENT RESEARCH | 2020年 / 81卷 / 02期
关键词：
Alzheimer's disease; antioxidant activity; BACE1; molecular docking; molecular hybridization; BETA-SECRETASE INHIBITORS; ALZHEIMERS-DISEASE; DERIVATIVES; ACIDS;
D O I：
10.1002/ddr.21585
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The proteolytic enzyme beta-secretase (BACE1) plays a central role in the synthesis of the pathogenic beta-amyloid peptides (A beta) in Alzheimer's disease (AD), antioxidants could attenuate the AD syndrome and prevent the disease progression. In this study, BACE1 inhibitors (D1-D18) with free radical-scavenging activities were synthesized by molecular hybridization of 2-aminopyridine with natural antioxidants. The biological activity evaluation showed that D1 had obvious inhibitory activity against BACE1, and strong antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2 '-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS(+center dot)) assay, which could be used as a lead compound for further study.
引用
收藏
页码：206 / 214
页数：9
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