Antitumor Agents LIII: The Effects of Daphnoretin on Nucleic Acid and Protein Synthesis of Ehrlich Ascites Tumor Cells

Daphnoretin, a dicoumaryl ether, has been shown to inhibit growth of Ehrlich ascites carcinoma cells. Dosing for three days at 6 mg/kg/day reduced the cell number per milliliter by 60%. In vitroDNA and protein synthesis studies demonstrated an ID50≅ 0.194 mMand ID50≅ 0.340 mM, respectively, for daphnoretin. Subsequently it has been shown that in vivonucleic acid and protein synthesis were inhibited. Major sites in the DNA synthetic pathway inhibited significantly by daphnoretin were dihydrofolate reductase, orotidine monophosphate decarboxylase, thymidylate monophosphate kinase, and ribonucleotide reductase. Reduction of in vitrooxidative phosphorylation processes and acid hydrolytic enzymes were also inhibited in the presence of daphnoretin.