Discovery of a novel multifunctional carbazole-aminoquinoline dimer for Alzheimer's disease: copper selective chelation, anti-amyloid aggregation, and neuroprotection

被引：18
作者：
Zhang, Xiao [1 ,2 ]
Wang, Ying [3 ]
Wang, Sheng-nan [2 ,4 ,5 ,6 ]
Chen, Qiu-he [2 ,4 ,5 ]
Tu, Ya-lin [2 ,4 ,5 ]
Yang, Xiao-hong [2 ,4 ,5 ,7 ]
Chen, Jing-kao [2 ,4 ,5 ]
Yan, Jin-wu [8 ]
Pi, Rong-biao [2 ,4 ,5 ,9 ]
Wang, Yan [1 ]
机构：
[1] Guangdong Pharmaceut Univ, Sch Tradit Chinese Med, Guangzhou 510006, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China
[3] Guangdong Pharmaceut Univ, Sch Chem & Chem Engn, Guangzhou 510006, Guangdong, Peoples R China
[4] Int Joint Lab SYSU PolyU HK Novel Antidementia Dr, Guangzhou 510006, Guangdong, Peoples R China
[5] Sun Yat Sen Univ, Natl & Local United Engn Lab Druggabil & New Drug, Guangzhou 510006, Guangdong, Peoples R China
[6] Cent S Univ, Dept Pharm, Xiangya Hosp, Changsha 410008, Hunan, Peoples R China
[7] Chongqing Hlth Ctr Women & Children, Dept Pharm, Chongqing 400013, Peoples R China
[8] South China Univ Technol, Sch Biosci & Bioengn, Guangzhou 510006, Guangdong, Peoples R China
[9] Sun Yat Sen Univ, Zhongshan Sch Med, Guangdong Prov Key Lab Brain Funct & Dis, Guangzhou 510080, Guangdong, Peoples R China
来源：
MEDICINAL CHEMISTRY RESEARCH | 2018年 / 27卷 / 03期
基金：
中国国家自然科学基金;
关键词：
Multifunctional dimer; Copper selective chelation; Anti-amyloid aggregation; Neuroprotection; Alzheimer's disease; AMINOPROPYL CARBAZOLES; OXIDATIVE STRESS; NATURAL-PRODUCTS; MOUSE MODEL; DERIVATIVES; AGENTS; BETA; INVOLVEMENT; MECHANISMS; INHIBITORS;
D O I：
10.1007/s00044-017-2101-9
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A novel multifunctional carbazole-aminoquinoline dimer PZ001 was designed, synthesized, and evaluated. The results indicated that PZ001 possessed selective copper chelation, and inhibited copper-induced A beta(1-42) aggregation. Furthermore, PZ001 exerted powerful neuroprotection against glutamate-induced HT22 cell death. These results suggest that PZ001 may be a promising multifunctional anti-AD compound.
引用
收藏
页码：777 / 784
页数：8
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