5-substituted-2-thiohydantoin analogs as a novel class of antitumor agents

被引:112
作者
AlObaid, AM
ElSubbagh, HI
Khodair, AI
Elmazar, MMA
机构
[1] KING SAUD UNIV,COLL PHARM,DEPT PHARMACEUT CHEM,RIYADH 11451,SAUDI ARABIA
[2] KING SAUD UNIV,COLL PHARM,DEPT PHARMACOL,RIYADH 11451,SAUDI ARABIA
[3] TANTA UNIV,FAC EDUC,DEPT CHEM,KAFR EL SHEIKH BRANCH,TANTA,EGYPT
关键词
antitumor screening; nucleosides; 2-thiohydantoins;
D O I
10.1097/00001813-199611000-00009
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Certain series of 2-thiohydantoin derivatives, carrying various substituents at position 5 such as 5 bromo-2-thienylmethylene, 5-(2-carboxyphenylthio)-2-thienylmethyle and 2-methylene-4H-thieno[2,3-b][1]benzothio were evaluated for their antitumor activity. Compound 5-(5-bromo-2-thienylmethylene)-3-morpholinome tetra-O-acetyl-beta-D-glucopyranosylthio)hydantoin proved to possess a broad spectrum antitumor activity against a wide range of different human cell lines of nine tumor subpanels causing both cytostatic and cytotoxic effects, resulting in full panel median growth inhibition (GI(50)) and total growth inhibition (TGI), with a median lethal concentration (LC(50)) at 15.1, 41.7 and 83.2 mu M, respectively. On the other hand, compound 5-(5-bromo-2-thienylmethylene)-2-thiohydantoin and compound 5-(5-bromo-2-thienylmethylene)-3-phenyl-2-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl-thio)hydantoin showed potential selectivity against leukemia cell lines. Further derivatization of these compounds, deduced from the obtained tentative structure-activity relationships, may lead to more potent agents.
引用
收藏
页码:873 / 880
页数:8
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