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.
Sztanke
Krzysztof
K
Chair and Department of Medical Chemistry, Medical University, 4 Staszica Street, Lublin, Poland. krzysztof.sztanke@am.lublin.pl
Pasternak
Kazimierz
K
Sztanke
Małgorzata
M
Kandefer-Szerszeń
Martyna
M
Kozioł
Anna E
AE
Dybała
Izabela
I
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008968:Molecular Conformation; D009362:Neoplasm Metastasis; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
D000970:Antineoplastic Agents; D014227:Triazines; C093444:1,2,4-triazine