Synthesis and antiproliferative activity of cytidine-5'-alkylphosphonophosphates and structurally related compounds.
The chemical synthesis of cytidine-5'-alkyl- and cytidine-5'-alkyl (acyl)deoxyglycerophosphonophosphates is reported. The compounds obtained represent a novel class of cytostatically active agents based on phospholipids, which inhibit the growth of various tumor cell lines in vitro. They are phosphono analogs of the cytidine-5'-diphosphate-diacylglycerol (CDP-DAG) possessing a structurally modified lipid moiety and a phospholipase C-resistant P-C bond. The antiproliferative efficacy of the cytidine-5'-alkylphosphonophosphates strongly depends on the alkyl chain length. The cytidine-5'-hexadecylphosphonophosphate was found to be the most effective compound tested in this study. Its cytostatic effect was distinctly higher than that of the alkyl(acyl) deoxyglycero derivatives and of the corresponding diphosphates. The structure of the new compounds were confirmed by fast atom bombardment mass spectrometry (FAB). The FAB fragmentation pattern is discussed.
Brachwitz
H
H
Freie Universität Berlin, Universitätsklinikum Benjamin Franklin, Abt. Hämatologie and Onkologie, Germany.
Lachmann
U
U
Thomas
Y
Y
Bergmann
J
J
Berdel
W E
WE
Langen
P
P
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003565:Cytidine Diphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D010743:Phospholipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010743:Phospholipids; D003565:Cytidine Diphosphate