Synthesis and biological evaluation of some 4′-C-(hydroxymethyl)- α- and -β-D-arabinofuranosyl pyrimidine and adenine nucleosides

Jean François Griffon, Sue C. Shaddix, William B. Parker, Ashraf Al Madhoun, Staffan Eriksson, John A. Montgomery, John A. Secrist

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

A series of 4′-C-(hydroxymethyl) analogs of pyrimidine and purine nucleosides have been prepared utilizing standard methodologies, and the α and β anomers were separated. These analogs are part of our continuing efforts to identify new anticancer drugs as well as to explore the substrate specificities of these analogs with the initial activating enzymes in the metabolic pathway leading to nucleoside triphosphates. Although not cytotoxic to CCRF-CEM cells (an acute lymphoblastic leukemia of T-cell origin), many of these compounds were utilized as substrates for the various human nucleoside kinases, including deoxycytidine kinase, thymidine kinase 1, and thymidine kinase 2. Because the 4′-C-(hydroxymethyl) analog of arabinofuranosyl cytosine was identified as a good substrate with deoxycytidine kinase, its metabolism in CEM cells was evaluated. These results indicated that nucleosides with this modification could be activated in human cells without cytotoxicity, which suggested that they should be examined for antiviral activity.

Original languageEnglish
Pages (from-to)1063-1087
Number of pages25
JournalCollection of Czechoslovak Chemical Communications
Volume71
Issue number7
DOIs
Publication statusPublished - 1 Jul 2006

Keywords

  • 4′-C-(Hydroxymethyl)nucleosides
  • 4′-C-Branched nucleosides
  • Cytotoxicity
  • Deoxycytidine kinase
  • Glycosidation
  • Phosphorylation
  • Purines
  • Pyrimidines

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