Synthesis and antiproliferative activity characterization of new imidazothiazolotriazine oxindolylidene derivatives containing various substituents in the oxindole ring

Condensation of 1,3-diethyltetrahydroimidazo[4,5-e]thiazolo[3,2-b][1,2,4]triazine-2,7-dione with isatins followed by framework rearrangement in the thiazolotriazine moiety was used to synthesize two new series of oxindolylidenetetrahydroimidazo[4,5-e]thiazolo- [3,2-b][1,2,4]triazine-2,7-diones and oxindolylidenetetrahydroimidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazine-2,8-diones containing various substituents in the oxindole moiety. The obtained compounds were tested for antiproliferative activity. The greatest activity was observed in the case of 1-alkyl-7-methyloxindolylidene derivatives of imidazo[4,5-e]thiazolo[2,3-c]triazine, which not only inhibited the growth of more than half of the studied cell lines, but also caused cell death in the SF-539 cell line (central nervous system cancer, mean growth percent -7.82%) and MDA-MB-435 (melanoma, -30.97 and -13.64%).