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

  • Bioorg Med Chem Lett. 2004 Nov 1;14(21):5401-5. doi: 10.1016/j.bmcl.2004.08.017.
Han Chen  1 ,  Yun-Hua Fan ,  Amarnath Natarajan ,  Yuhong Guo ,  Julia Iyasere ,  Fred Harbinski ,  Lia Luus ,  William Christ ,  Huseyin Aktas ,  Jose A Halperin
Affiliations
  • 1. Laboratory for Translational Research, Harvard Medical School, Cambridge, MA 02139, USA.
PMID: 15454234 DOI: 10.1016/j.bmcl.2004.08.017
Abstract

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 microM GI(50) mediated by inhibition of translation initiation, which involves partial depletion of intracellular CA(2+) stores and strong phosphorylation of eIF2alpha.