Cytostatic activity of pyridazine derivatives. Part II. In vitro studies on halogen derivatives of 6-pyridazinone and 3,6-pyridazinedione.
Cytotoxicity f 22 halogen derivatives of 6-pyridazinone (6-PD-ones) and 2-methyl-3,6-pyridazinedione (3,6-PD-diones) was studied on KB and HeLa human tumor tissue cultures. 15 compounds with ED50 activity values ranging between 0.043-2.8 micrograms/ml (9.7 x 10(-8)-9.9 x 19(-6)M) on the base of DR and D, NCI, NIH Bethesda criterium were qualified for further in vivo investigation. The presence of halogen at C-5 position determines the cytotoxic activity of 6-PD-ones and 3,6-PD-diones. Additional halogen introduction into heterocyclic ring C-4 increases the activity both meta and para bromophenyl derivatives of 6-PD-ones and, proportionally to the number of bromines, of 3,6-PD-diones. The acceptable activity demonstrated also the halogen unsubstituted 3,6-PD-diones. The 3,6-PD-dione activity seems to depend in small degree on the kind of substituent in benzene ring.
D000970:Antineoplastic Agents; D002478:Cells, Cultured; D046508:Culture Techniques; D006367:HeLa Cells; D006801:Humans; D011724:Pyridazines / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D011724:Pyridazines