title: Design, synthesis and cytotoxicity of a new series of isoxazolidine based nucleoside analogues.
abstract: 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.
authors.affiliation: Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Poland. dorota.piotrowska@umed.lodz.pl
authors.forename: Dorota G
authors.initials: DG
authors.lastname: Piotrowska
authors.forename: Marcin
authors.initials: M
authors.lastname: Cieślak
authors.forename: Karolina
authors.initials: K
authors.lastname: Królewska
authors.forename: Andrzej E
authors.initials: AE
authors.lastname: Wróblewski
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020014:K562 Cells; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D063065:Organophosphonates / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007555:Isoxazoles; D009705:Nucleosides; D063065:Organophosphonates