TY - JOUR
T1 - Synthesis and biological evaluation of thiazolidine-2,4-dione and 2,4-thione derivatives as inhibitors of translation initiation
AU - Chen, Han
AU - Fan, Yun Hua
AU - Natarajan, Amarnath
AU - Guo, Yuhong
AU - Iyasere, Julia
AU - Harbinski, Fred
AU - Luus, Lia
AU - Christ, William
AU - Aktas, Huseyin
AU - Halperin, Jose A.
N1 - Funding Information:
These studies were supported in part by NIH National Cooperative Drug Discovery Group (NCDDG) grant S U19 CA87427 and NIH CA78411. The authors wish to thank Drs. M. Tosteson and D. C. Tosteson for continuous support and Dr. Michael Chorev for comments and discussion.
PY - 2004/11/1
Y1 - 2004/11/1
N2 - A series of 2′-benzyloxy-5′-substituted-5-benzylidene- thiazolidine-2,4-thione and -dione derivatives was synthesized and evaluated 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 GI 50 mediated by inhibition of translation initiation, which involves partial depletion of intracellular Ca 2+ stores and strong phosphorylation of eIF2Iα.
AB - A series of 2′-benzyloxy-5′-substituted-5-benzylidene- thiazolidine-2,4-thione and -dione derivatives was synthesized and evaluated 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 GI 50 mediated by inhibition of translation initiation, which involves partial depletion of intracellular Ca 2+ stores and strong phosphorylation of eIF2Iα.
KW - Cancer therapy
KW - Thiazolidine-2,4-dione
KW - Thiazolidine-2,4-thione
KW - Translation initiation inhibitors
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U2 - 10.1016/j.bmcl.2004.08.017
DO - 10.1016/j.bmcl.2004.08.017
M3 - Article
C2 - 15454234
AN - SCOPUS:5344277530
SN - 0960-894X
VL - 14
SP - 5401
EP - 5405
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 21
ER -