Synthesis and biological activity of certain 4'-thio-D-arabinofuranosylpurine nucleosides.

Academic Article

Abstract

  • A series of 4'-thio-D-arabinofuranosylpurine nucleosides was prepared and evaluated as potential anticancer agents. The details of a convenient and high-yielding synthesis of the carbohydrate precursor 1-O-acetyl-2,3,5-tri-O-benzyl-4-thio-D-arabinofuranose (6) are presented. Proof of structure and configuration at all chiral centers of the nucleosides was obtained through an X-ray crystal structure of 9alpha as well as through NOE experiments on 9beta and 9alpha. All six target compounds were evaluated in a series of human cancer cell lines in culture. Two target compounds, beta anomers with diaminopurine (12) and guanine (16) as the bases, had significant cytotoxicity. One of these compounds (12) was selected for animal studies but was found to have no selectivity at the maximum tolerated dose in the murine colon 36 tumor model.
  • Published In

    Keywords

  • Adenosine, Antineoplastic Agents, Cell Division, Crystallography, X-Ray, Drug Screening Assays, Antitumor, Humans, Magnetic Resonance Spectroscopy, Molecular Conformation, Purine Nucleosides, Structure-Activity Relationship, Tumor Cells, Cultured
  • Digital Object Identifier (doi)

    Pubmed Id

  • 10440268
  • Author List

  • Secrist JA; Tiwari KN; Shortnacy-Fowler AT; Messini L; Riordan JM; Montgomery JA; Meyers SC; Ealick SE
  • Start Page

  • 3865
  • End Page

  • 3871
  • Volume

  • 41
  • Issue

  • 20