New nucleoside-5′-alkylphosphonophosphates and related compounds containing 2′-deoxycytidine, thymidine and adenosine as nucleoside component. Syntheses and their effects on tumor cell growth in vitro

• Published in: Chemistry and physics of lipids 1997-05, Vol.87 (1), p.31-39
• Main Authors: Brachwitz, H, Thomas, Y, Bergmann, J, Langen, P, Berdel, W.E
• Format: Article
• Language: English
• Subjects: Adenosine - analysis; Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiproliferative activity; Breast Neoplasms; Cell Division - drug effects; Chromatography, Thin Layer; Deoxycytidine - analysis; Electrospray ionizations mass spectrometry (ESI-MS); Fast atom bombardement mass spectrometry (FAB-MS); Female; Humans; Mass Spectrometry; Molecular Structure; Nucleoside-5′-alkyldiphosphate; Nucleoside-5′-alkylphosphonophosphate; Nucleoside-phospholipid conjugates; Nucleotides - chemical synthesis; Nucleotides - chemistry; Nucleotides - pharmacology; Organophosphorus Compounds - chemical synthesis; Organophosphorus Compounds - chemistry; Organophosphorus Compounds - pharmacology; Phospholipids - chemical synthesis; Phospholipids - pharmacology; Thymidine - analysis; Tumor Cells, Cultured
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/S0009-3084(97)00021-2

Recent studies have shown that phosphono analogs of cytidine-5′-diphosphate diacylglycerol (CDP-DAG) possessing a structurally modified lipid moiety exhibit antiproliferative activity in vitro. As an extension of our previous work we tried to elucidate whether the presence of the cytidine component is necessary for cytostatic activity. In this context we have synthesized similarly structured nucleoside-phospholipid conjugates containing nucleoside components other than cytidine, which also do not exhibit cytostatic properties as such. The compounds include 5′-alkyldiphosphates and 5′-alkylphosphonophosphates of 2′-deoxycytidine, thymidine and adenosine with different alkyl chain length as well as selected 3-hexadecyl-2-chloro-2-deoxyglycero-(1)-diphosphates and -phosphonophosphates of these nucleosides. The chemical structures of the newly synthesized nucleoside-phospholipid conjugates were confirmed by fast atom bombardment (FAB) and electrospray ionization (ESI) mass spectrometry. It was found that these compounds also inhibit the cell growth of different human cell lines, i.e. the presence of the cytidine component is not a necessary prerequisite for the antiproliferative activity of these nucleoside-phospholipid conjugates.