Synthesis and antiproliferative activity of alkylphosphocholines.
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 omega-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.
Agresta
Mandy
M
Dipartimento di Chimica, Materiali, Ingegneria Chimica Giulio Natta, Politecnico di Milano and CNR, Istituto di Chimica del Riconoscimento Molecolare Adolfo Quilico, Via Mancinelli 7, 20131 Milano, Italy.
D'Arrigo
Paola
P
Fasoli
Ezio
E
Losi
Daniele
D
Pedrocchi-Fantoni
Giuseppe
G
Riva
Simona
S
Servi
Stefano
S
Tessaro
Davide
D
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D019169:Jurkat Cells; D020014:K562 Cells; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D010739:Phospholipase D / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts / Q000032:analysis; D013936:Thymidine / Q000378:metabolism
D000970:Antineoplastic Agents; D013778:Tetrazolium Salts; D010767:Phosphorylcholine; C105905:perifosine; C039128:miltefosine; D010739:Phospholipase D; D013936:Thymidine