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

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 μM GI50 mediated by inhibition of translation initiation, which involves partial depletion of intracellular Ca2+ stores and strong phosphorylation of eIF2α.