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(1 H )-one 1f was found to have the most marked antiproliferative activity toward the tested cell lines ( 1f : IC 50 = 20.6 , 23.7, and 6.4 μ M, respectively). The IC 50 value of thioglycoluril 1f against normal human embryonic kidney cells HEK293 was 72.5 μ M, which appeared to be 3–11-fold higher than IC 50 values of 1f against human cancer cells.