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.
D000332:Aerobiosis; D000693:Anaerobiosis; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000201:enzymology / Q000378:metabolism*; D002952:Citric Acid Cycle / Q000187:drug effects; D003499:Cyclic S-Oxides / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006019:Glycolysis / Q000187:drug effects; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000037:antagonists & inhibitors; D010085:Oxidative Phosphorylation / Q000187:drug effects; D012334:RNA, Neoplasm / Q000096:biosynthesis
D000970:Antineoplastic Agents; D003499:Cyclic S-Oxides; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C031794:3-(chloromethyl)thiochromone 1,1-dioxide; D009964:Orotidine-5'-Phosphate Decarboxylase