A Phospholipid Derivative of Cytosine Arabinoside and Its Conversion to Phosphatidylinositol by Animal Tissue

Abstract
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-dipalmitin 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.

This publication has 25 references indexed in Scilit: