Benzo[e]isoindole-1,3-diones as Potential Inhibitors of Glycogen Synthase Kinase-3 (GSK-3). Synthesis, Kinase Inhibitory Activity, Zebrafish Phenotype, and Modeling of Binding Mode

被引：46

作者：

Zou, Haixia ^{[1
,2
,3
]}

Zhou, Liyan ^{[1
]}

Li, Yuanzhen ^{[1
]}

Cui, Yi ^{[1
]}

Zhong, Hanbing ^{[1
]}

Pan, Zhengying ^{[1
]}

Yang, Zhen ^{[1
,2
,3
]}

Quan, Junmin ^{[1
]}

机构：

[1] Peking Univ, Shenzhen Grad Sch, Lab Chem Genom, Shenzhen, Peoples R China

[2] Peking Univ, Coll Chem, BNLMS, Beijing 100871, Peoples R China

[3] Peking Univ, Minist Educ, Key Lab Bioorgan Chem & Mol Engn, Beijing 100871, Peoples R China

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 53卷 / 03期

基金：

美国国家科学基金会;

关键词：

SELECTIVE INHIBITORS; GSK-3; TARGET; ROLES;

D O I：

10.1021/jm9013373

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Benzo[e]isoindole-1,3-dione derivatives were synthesized, and the effects on GSK-3 beta activity and zebrafish embryo growth were evaluated. A series of derivatives show obvious inhibitory activity against GSK-3 beta. The most potent inhibitor, 7,8-dimethoxy-5-methylbenzo[e]isoindole-1,3-dione (8a), shows nanomolar IC50 and obvious phenotype on zebrafish embryo growth associated with the inhibition of GSK-3 beta at low micromolar concentration. The interaction mode between 8a and GSK-3 beta was characterized by computational modeling.

引用

页码：994 / 1003

页数：10

共 32 条

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