Synthesis and In Vitro Antitumor Activity of 2′‐Deoxy‐5‐fluorouridylyl‐(3′→5′)‐2′‐deoxy‐5‐fluoro‐N⁴‐octadecylcytidine: A New Amphiphilic Dinucleoside Phosphate

The new amphiphilic dinucleoside phosphate, 2′‐deoxy‐5‐fluorouridylyl‐(3′→5′)‐2′‐deoxy‐5‐fluoro‐ N 4 ‐octadecylcytidine ( 4 ) was synthesized on a gram scale, using the 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 adenocarcinoma cell line MIA PaCa 2, the amphiphilic dimer was significantly more effective than the parent monomeric 5FdU. The IC 50 of the dimer was 10 μg/ml when applied as an aqueous solution and 12 μg/ml when given as a liposome dispersion, whereas with 5FdU the IC 50 concentration was not reached within the concentration range used.