A phospholipid derivative of cytosine arabinoside and its conversion to phosphatidylinositol by animal tissue.
We have synthesized an analog (ara-CDP-DL-dipalmitin) of cytidine diphosphate diglyceride (CDP-diglyceride) in which the antitumor drug, cytosine arabinoside, is substituted for the cytidine moiety. Enzymes in rat and human liver convert this analog to phosphatidylinositol, thereby releasing cytosine arabinoside-5'-monophosphate, an obligatory intermediate in the activation of cytosine arabinoside. Unlike cytidine diphosphate diglyceride, however, ara-CDP-DL-diapalmitin is not an efficient substrate for phosphatidylglycerophosphate synthesis in liver or phosphatidylserine in Escherichia coli. The antitumor activity of ara-CDP-DL-dipalmitin in mice bearing L5178Y leukemia is described.
D000818:Animals; D001711:Biotransformation; D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase / Q000378:metabolism; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D004075:Diglycerides / Q000378:metabolism*; D005989:Glycerides / Q000378:metabolism*; D006801:Humans; D007942:Leukemia, Experimental / Q000188:drug therapy; D008099:Liver / Q000378:metabolism; D051379:Mice; D010715:Phosphatidylglycerols; D010716:Phosphatidylinositols / Q000096:biosynthesis; D010770:Phosphotransferases / Q000378:metabolism; D051381:Rats
D004075:Diglycerides; D005989:Glycerides; D010715:Phosphatidylglycerols; D010716:Phosphatidylinositols; D003561:Cytarabine; D010770:Phosphotransferases; D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase