title: Design, synthesis, antiviral, and cytostatic evaluation of novel isoxazolidine analogs of homonucleotides.
abstract: Moderate diastereoselectivities (d.e. 2-62%) of isoxazolidine homonucleotides were observed for cycloadditions between N-methyl-C-(diethoxyphosphoryl)nitrone and N-allyl nucleobases, with trans-isoxazolidines predominating. The stereochemistry of the substituted isoxazolidines was established based on 2D NOE experiments performed for uracil-containing cycloadducts. The cis- and trans-isoxazolidine phosphonates obtained herein were evaluated in vitro for activity against a broad range of DNA and RNA viruses. None of the compounds were endowed with antiviral activity at subtoxic concentrations, but some of them were found to inhibit the proliferation of L1210 cells with IC50 values in the range of 33-100 µM.
authors.affiliation: Faculty of Pharmacy, Bioorganic Chemistry Laboratory, Medical University of Łódź, Łódź, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Łysakowska
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Dorota G
authors.initials: DG
authors.lastname: Piotrowska
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D061565:Cycloaddition Reaction; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004285:Dogs; D015195:Drug Design; D005347:Fibroblasts / Q000187:drug effects / Q000821:virology; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007555:Isoxazoles / Q000737:chemistry*; D061985:Madin Darby Canine Kidney Cells; D015394:Molecular Structure; D009711:Nucleotides / Q000737:chemistry*; D013237:Stereoisomerism; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology; D014709:Vero Cells; D010948:Viral Plaque Assay
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D007555:Isoxazoles; D009711:Nucleotides
keywords: Antiproliferative agents; Cycloaddition; Isoxazolidines