Synthesis and antiproliferative activity of alkylphosphocholines

• Published in: Chemistry and physics of lipids 2003-12, Vol.126 (2), p.201-210
• Main Authors: Agresta, Mandy, D’Arrigo, Paola, Fasoli, Ezio, Losi, Daniele, Pedrocchi-Fantoni, Giuseppe, Riva, Simona, Servi, Stefano, Tessaro, Davide
• Format: Article
• Language: English
• Subjects: Alkylphosphocholines; Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Antitumor activity; Cell Division - drug effects; Cell Line; HeLa Cells; Hemolysis - drug effects; Humans; Inhibitory Concentration 50; Jurkat Cells; K562 Cells; Macrophages - cytology; Macrophages - drug effects; Macrophages - metabolism; Mice; Miltefosine; Molecular Structure; Phospholipase D - metabolism; Phosphorylcholine - analogs & derivatives; Phosphorylcholine - chemical synthesis; Phosphorylcholine - chemistry; Phosphorylcholine - metabolism; Phosphorylcholine - pharmacology; Phosphorylcholine - toxicity; Structure-Activity Relationship; Tetrazolium Salts - analysis; Thymidine - metabolism
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/j.chemphyslip.2003.08.002

Alkylphosphocholines (APC) with one or more methylene groups in the alkyl chain replaced by oxygen atoms or carbonyl groups, or both have been assembled modularly using ω-diols as central building blocks. Out of 25 new compounds of this kind, 11 were evaluated for their antiproliferative activity on four cell lines and compared with miltefosine to evaluate their hemolytic activity (HA) and cytotoxicity on non-tumoral cells (MT2), used as markers of adverse effects. Compound 13 was more active on cancer cell lines than on non-tumoral cells and the data were similar for MTT and thymidine incorporation assays. It had less HA than miltefosine. Compound 13 could therefore be a candidate for the preparation of compounds with higher cytotoxicity on cancer cells and lower general toxicity.