Synthesis and cytostatical evaluation of cytidine- and adenosine-5′-hexadecylphosphate and their phosphonate analogs

Four phospholipid conjugates containing the non-cytotoxic nucleosides cytidine and adenosine were prepared by condensation reactions, and their cytotoxic activity was tested in vitro against the human immortalized mammary epithelial cell H184 A(1)N(4), the human mammary tumor cells MaTu and MCF7 and the B lymphoblast cell line Daudi. The synthesized compounds showed considerable activity towards H184 A(1)N(4), MaTu and Daudi cells, but they were not effective against MCF7 cells. The phosphorus moiety-either monophosphate or monophosphonate-does not influence the effectiveness of the phospholipid derivatives in the case of the solid tumor cell lines and H184 A(1)N(4). The leukemic Daudi cell line is strongly sensitive towards the different types of ester as well as to the type of the nucleoside component. Adenosine-5'-hexadecylphosphate proved to be the most potent compound among the substances prepared (IC50: 9.0 mu mol). (C) 1997 Elsevier Science Ireland Ltd.