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Synthesis and In Vitro Antitumor Activity of 2′‐Deoxy‐5‐fluorouridylyl‐(3′→5′)‐2′‐deoxy‐5‐fluoro‐ N 4 ‐octadecylcytidine: A New Amphiphilic Dinucleoside Phosphate
Author(s) -
Schott Herbert,
Ludwig Peter S.,
Gansauge Frank,
Gansauge Susanne,
Schwendener Reto A.
Publication year - 1997
Publication title -
liebigs annalen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0947-3440
DOI - 10.1002/jlac.199719970220
Subject(s) - chemistry , amphiphile , in vitro , dimer , phosphate , aqueous solution , stereochemistry , combinatorial chemistry , biochemistry , copolymer , organic chemistry , polymer
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.