Discovery of 3-(2-aminoethyl)-5-(3-phenyl-propylidene)-thiazolidine-2,4-dione as a dual inhibitor of the Raf/MEK/ERK and the PI3K/Akt signaling pathways

被引：35
|
作者：
Li, Qianbin [1 ]
Wu, Jingde [1 ]
Zheng, Hui [2 ]
Liu, Kai [1 ]
Guo, Tai L. [3 ]
Liu, Yuying [2 ]
Eblen, Scott T. [2 ]
Grant, Steven [4 ]
Zhang, Shijun [1 ]
机构：
[1] Virginia Commonwealth Univ, Dept Med Chem, Sch Pharm, Richmond, VA 23298 USA
[2] Med Univ S Carolina, Dept Cell & Mol Pharmacol, Charleston, SC 29425 USA
[3] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA
[4] Virginia Commonwealth Univ, Dept Internal Med & Biochem, Richmond, VA 23298 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 15期
关键词：
Dual pathway inhibitor; Raf/MEK/ERK; PI3K/Akt; Thiazolidine-2,4-dione; PROTEIN-KINASE PATHWAY; HUMAN LEUKEMIA-CELLS; PROSTATE-CANCER; MOUSE MODEL; INVOLVEMENT; APOPTOSIS; 3-KINASE; GROWTH; RAS;
D O I：
10.1016/j.bmcl.2010.06.030
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A thiazolidine-2,4-dione derivative, 3-(2-aminoethyl)-5-(3-phenyl-propylidene)-thiazolidine-2,4-dione (2), was identified as a dual inhibitor of the Raf/MEK/ extracellular signal-regulated kinase (ERK) and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascades. The discovered compound inhibited cell proliferation, induced early apoptosis, and arrested cells in G(0)/G(1) phase in human leukemia U937 cells. These results indicate its potential as a new lead compound to develop novel dual signaling pathway inhibitors and anticancer agents. Published by Elsevier Ltd.
引用
收藏
页码：4526 / 4530
页数：5
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