Effects of 3-chloromethylthiochromone-1,1-dioxide on nucleic acid, protein, and aerobic and anaerobic metabolism of Ehrlich ascites tumor cells.

3-Chloromethylthiochromone-1,1-dioxide was observed to be a potent inhibitor of Ehrlich ascites carcinoma growth and a moderate inhibitor of P-388 lymphocytic leukemia growth at 10 mg/kg/day. Preliminary in vitro studies showed that the agents significantly inhibited RNA and DNA synthesis in Ehrlich ascites cells. In vivo studies after dosing on Days 6, 7, and 8 demonstrated the same reductions in nucleic acid synthesis and a moderate reduction in protein synthesis. The primary site of nucleic acid synthesis, which was blocked by 3-chloromethylthiochromone, was at orotidine monophosphate decarboxylase in the primidine pathway. Other enzymes, in anaerobic and aerobic glycolysis, which were blocked include hexokinase, phosphofructokinase, succinic and alpha-ketoglutarate dehydrogenases, as well as States 3 and 4 of oxidative phosphorylation.