Synthesis and Biological Evaluation of Novel Pyrimido[4,5-b]quinoline-2,4-dione Derivatives as MDM2 Ubiquitin Ligase Inhibitors

被引：4

作者：

Dou, Xiaoxue ^{[1
]}

Li, Xin ^{[1
]}

Tao, Liu ^{[1
]}

Hu, Chunqi ^{[1
]}

Zhang, Lei ^{[2
]}

He, Qiaojun ^{[2
]}

Yang, Bo ^{[2
]}

Hu, Yongzhou ^{[1
]}

机构：

[1] Zhejiang Univ, Coll Pharmaceut Sci, ZJU ENS Joint Lab Med Chem, Hangzhou 310058, Zhejiang, Peoples R China

[2] Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmacol & Toxicol, Hangzhou 310058, Zhejiang, Peoples R China

来源：

MEDICINAL CHEMISTRY | 2013年 / 9卷 / 04期

基金：

中国国家自然科学基金;

关键词：

Cytotoxic activity; MDM2 E3 ligase inhibitory activity; p53-MDM2 binding inhibitor; pyrimido[4,5-b]quinoline-2,4-dione;

D O I：

10.2174/1573406411309040012

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of pyrimido[4,5-b]quinoline-2,4-dione derivatives was synthesized and evaluated for their cytotoxic activities in vitro against five human cancer cell lines. Selected compounds were tested for their MDM2 E3 ligase inhibitory activities and p53-MDM2 binding inhibitory activities. Among tested compounds, four sulfur-containing compounds (4-7) displayed enhanced cytotoxic activities and better MDM2 E3 ligase inhibitoty activities in comparison with that of HLI98c. Three compounds (4-6) showed better p53-MDM2 binding inhibitory potency with IC50 values ranging from 1.3 mu M to 9.0 mu M.

引用

页码：581 / 587

页数：7