Synthesis and antiproliferative potency of 9-beta-D-arabinofuranosyl-2-fluoroadenine phospholipid adducts

Three novel alkylphospholipid and four novel O-alkylglycerophospholipid der ivatives of fludarabine (F-ara-AMP), known as a drug for the clinical treat ment of chronic lymphocytic leukemia, were synthesized. The antiproliferati ve activity was determined in comparison to the parent nucleoside fludarabi ne in an immortalized but nontumorigenic human mammary epithelial cell line (H 154 A1N4), in two human breast tumor cell lines (MaTu and MCF7), and in two leukemic cell lines (HL 60 and Daudi). Fludarabine inhibited the growt h of the leucemic cell lines very effectively. The breast tumor cell lines responded with much less sensitivity. The antiproliferative potency of the new compounds strongly depended on the chemical structure of the lipid comp onent, and derivatives with a high effectiveness against one or both of the breast tumor cell lines were described. (C) 1999 Elsevier Science Ltd. All rights reserved.