THE CYTOTOXIC ACTIVITY OF 1-ACYL-4,4-DIETHYL-3,5-PYRAZOLIDINEDIONE AND 1,2-DIACYL-4,4-DIETHYL-3,5-PYRAZOLIDINEDIONE

The 1-acyl- and 1,2-diacyl-4,4-diethyl-3,5-pyrazolinediones proved to be cytotoxic against the growth of a number of cell lines, including m urine and human leukemias, HeLa suspended carcinoma, colon adencarcino ma SW480, KB nasopharynx and glioma tumors. Selected compounds were al so active in the human lung bronchogenic MB-9812, and osteosarcoma TE4 18 screens. These derivatives were active in vivo in the Ehrlich ascit es carcinoma screen in CF-1 mice at 8 mg/kg/day I.P. The mode of actio n in Tmolt3 leukemia cells showed that the compounds reduced de novo s ynthesis of purines and pyrimidines and inhibited dihydrofolate reduct ase and ribonucleoside reductase activities. The DNA molecule was not a target although limited DNA strand scission may be possible.