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：36

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

页码：4526 / 4530

页数：5

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