Crystal structure, antitumour and antimetastatic activities of disubstituted fused 1,2,4-triazinones

Molecular structure of 3,8-disubstituted 7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-ones (8–14) was confirmed by X-ray crystallography of 14. All the compounds were evaluated for their antitumour and antimetastatic activities in vitro. Furthermore, their cytotoxicities towards human normal cell line—HSF cells were established, allowing us to point out some structure–activity relationships. Among them, imidazotriazinone 12, revealing remarkable dose-dependent viability decreases in human myeloma RPMI 8226 cells, was found to be completely non-toxic towards normal HSF cells. In addition, heterobicycles 8–12 were proved to exhibit significant antimetastatic potentials in the motility assay.

Graphical abstractMolecular structure, antitumoural and antimetastatic activities in vitro of 3,8-disubstituted 7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-ones (8–14) are presented. Among them, first of all heterobicycle 12 was found to reveal remarkable dose-dependent viability decreases in human peripheral blood myeloma RPMI 8226 cells, without affecting human normal cell line—HSF cells. Furthermore, heterobicycles 8–12 were proved to exhibit significant antimetastatic potentials in the motility assay.Figure optionsDownload full-size imageDownload as PowerPoint slide