Substituted N-aminothioglycolurils containing thiosemicarbazone moiety and their cytotoxic activity in vitro.

A library of hybrid molecules bearing thioglycoluril and (hetero)aromatic aldehyde thiosemicarbazone moieties was synthesized via a tandem hydrazone formation-ring contraction reaction of 5,7-dialkyl-3-thioxoperhydroimidazo[4,5-e]-1,2,4-triazin-6-ones with (hetero)aromatic aldehydes. All synthesized compounds were tested for their cytotoxic activity against rhabdomyosarcoma, A549, and MS human cancer cell lines by MTT-assay. Among the derivatives, (E)-4-benzylideneamino-1,3-dimethyl-5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one 1f was found to have the most marked antiproliferative activity toward the tested cell lines (1f: IC[Formula: see text] 23.7, and 6.4 [Formula: see text]M, respectively). The IC[Formula: see text] value of thioglycoluril 1f against normal human embryonic kidney cells HEK293 was 72.5 [Formula: see text]M, which appeared to be 3-11-fold higher than IC[Formula: see text] values of 1f against human cancer cells.