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.