Synthesis and biological evaluation of thiazolidine-2,4-dione and 2,4-thione derivatives as inhibitors of translation initiation

被引:48
|
作者
Chen, H
Fan, YH
Natarajan, A
Guo, YH
Iyasere, J
Harbinski, F
Luus, L
Christ, W
Aktas, H
Halperin, JA [1 ]
机构
[1] Harvard Univ, Sch Med, Lab Translat Res, Cambridge, MA 02139 USA
[2] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
关键词
translation initiation inhibitors; cancer therapy; thiazolidine-2,4-thione; thiazolidine-2,4-dione;
D O I
10.1016/j.bmcl.2004.08.017
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
In an effort to generate novel translation initiation inhibitors for cancer therapy, a series of 2'-benzyloxy-5'-substituted-5-benzylidene-thiazolidine-2,4-thione and dione derivatives was synthesized and evaluated for activity in translation initiation specific assays. Several candidates of the 5-benzylidene-thiazolidine-2,4-diones (3c, 3d, and 3f) and -thiones (2b, 2e, and 2j), inhibit cell growth with low muM GI(50) mediated by inhibition of translation initiation, which involves partial depletion of intracellular Ca2+ stores and strong phosphorylation of eIF2alpha. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5401 / 5405
页数:5
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