Ih. Hall et al., THE CYTOTOXIC ACTIVITY OF 1-ACYL-4,4-DIETHYL-3,5-PYRAZOLIDINEDIONE AND 1,2-DIACYL-4,4-DIETHYL-3,5-PYRAZOLIDINEDIONE, Anticancer research, 15(1), 1995, pp. 199-204
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.