Design, synthesis and cytotoxicity of a new series of isoxazolidine based nucleoside analogues.

5-Arylisoxazolidin-3-yl-3-diethoxyphosphonates have been synthesized from N-methyl-C-diethoxyphosphorylnitrone and vinyl aryls in good yields and their transformation into the respective phosphonic acids has been accomplished via dealkylation procedure using trimethylsilyl bromide. Phosphonates having 1- and 2-naphthyl substituents at C5 in the isoxazolidine ring as well as the respective phosphonic acids have been found cytotoxic to HeLa and K562 cells with IC(50) in the 0.1-0.3 mM range. Preliminary studies on mechanism of action imply that intercalation to DNA is not responsible for their cytotoxic properties.