Cytostatic activity of pyridazine derivatives. I. In vitro studies on 1-methoxyphenylpyridazine-6-ones.
Cytotoxicity of 15 pyridazine derivatives was studied by tissue method on human KB and HeLA cell lines. Six compounds with ED50 activity values between 0.025 and 1.1 micrograms/ml/5.7 X 10(8) - 3.2 X 10(-6) M/were classified for further in vivo investigations. It seems that the halogen in C-5 position plays the main role in the cytotoxic activity of pyridazine-6-ones. The para position of methoxy C-4 group in the lateral benzene ring may be assumed as the next determinant of activity. On the basis of theoretical possibilities a hypothetical model of the role of C-5 halogen substituent in complementary hydrogen bonds with the purines of DNA has been proposed.
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006219:Halogens / Q000494:pharmacology; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009303:Nasopharyngeal Neoplasms / Q000473:pathology; D009305:Nasopharynx / Q000473:pathology; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D006219:Halogens; D011724:Pyridazines