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

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'-deo...

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Bibliographic Details
Published inLiebigs Annalen no. 2; pp. 413 - 417
Main Authors Schott, H, Ludwig, PS, Gansauge, F, Gansauge, S, Schwendener, RA
Format Journal Article
LanguageEnglish
Published DEERFIELD BEACH Wiley 01.02.1997
Subjects
Chemistry
Chemistry, Multidisciplinary
Physical Sciences
Science & Technology
5-FLUORO-2'-DEOXYURIDINE
liposomes
phosphotriester method
2'-deoxy-5-fluorouridine derivatives
DERIVATIVES
antitumor agents
MIA PaCa 2 pancreas tumor cell
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Summary: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 IC50 of the dimer was 10 mu g/ml when applied as an aqueous solution and 12 mu g/ml when given as a liposome dispersion, whereas with 5TdU the IC50 concentration was not reached within the concentration range used.
ISSN:0947-3440
DOI:10.1002/jlac.199719970220