SYNTHESIS AND IN-VITRO ANTITUMOR-ACTIVITY OF -(3'-]-5')-2'-DEOXY-5-FLUORO-N-4-OCTADECYLCYTIDINE - A NEW AMPHIPHILIC DINUCLEOSIDE PHOSPHATE

The new amphiphilic dinucleoside phosphate, -(3'-->5')-2'-deoxy-5-fluo ro-N-4-octadecylcytidine (4) was synthesized on a gram scale, using th e phosphotriester method, starting from the cytostatic drug 2'-deoxy-5 -fluorouridine (5FdU) and 2'-deoxy-5-fluoro-N-4-octadecylcytidine (1d) . In in vitro clonogenic growth assays using the human pancreatic aden ocarcinoma cell line MIA PaCa 2, the amphiphilic dimer was significant ly more effective than the parent monomeric 5FdU. The IC50 of the dime r was 10 mu g/ml when applied as an aqueous solution and 12 mu g/ml wh en given as a liposome dispersion, whereas with 5TdU the IC50 concentr ation was not reached within the concentration range used.