5-SUBSTITUTED-2-THIOHYDANTOIN ANALOGS AS A NOVEL CLASS OF ANTITUMOR AGENTS

Certain series of 2-thiohydantoin derivatives, carrying various substi tuents at position 5 such as 5 bromo-2-thienylmethylene, 5-(2-carboxyp henylthio)-2-thienylmethyle and 2-methylene-4H-thieno[2,3-b][1]benzoth io were evaluated for their antitumor activity. Compound 5-(5-bromo-2- thienylmethylene)-3-morpholinome tetra-O-acetyl-beta-D-glucopyranosylt hio)hydantoin proved to possess a broad spectrum antitumor activity ag ainst a wide range of different human cell lines of nine tumor subpane ls causing both cytostatic and cytotoxic effects, resulting in full pa nel 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-thienylme thylene)-2-thiohydantoin and compound ra-O-acetyl-beta-D-galactopyrano syl-thio)hydantoin showed potential selectivity against leukemia cell lines. Further derivatization of these compounds, deduced from the obt ained tentative structure-activity relationships, may lead to more pot ent agents.