Design, Synthesis and Cytotoxicity of a New Series of Isoxazolidine Based Nucleoside Analogues

作者：Piotrowska Dorota G^*; Cieslak Marcin; Krolewska Karolina; Wroblewski Andrzej E

来源：Archiv der Pharmazie, 2011, 344(5): 301-310.

DOI：10.1002/ardp.201000282

• Cytotoxic activity
• Isoxazolidines
• Nitrones
• Phosphonates
• Structure elucidation

5-Arylisoxazolidin-3-yl-3-diethoxyphosphonates have been synthesized from N-methyl-C-diethoxy-phosphorylnitrone 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.

• 出版日期2011-5