Synthesis, antiviral and antitumor activities investigations of a series of Ribavirin C-nucleoside analogue prodrugs

Bioorg Chem. 2022 May:122:105723. doi: 10.1016/j.bioorg.2022.105723. Epub 2022 Mar 5.

Abstract

Phosphoramidates obtained according to the ProTide strategy are known for their ability to increase the biological activity of various nucleosides. A series of such prodrugs of SRO-91, a non-natural ribofuranosyl-1,2,3-triazole C-nucleoside obtained by a synthetic sequence involving an indium mediated alkynylation and a Huisgen cycloaddition, was prepared and the antitumor activity on 3 strains of tumor cells was investigated. Two compounds 9a and 9c exhibited interesting cell proliferative inhibitions (IC50 = 2.5-12.1 µM) on two cell lines (pancreas and lung). Moreover, concerning the antiviral activity, another phosphoramidate 14 bearing a different aryl masking group exhibited an IC50 of 5 µM on Crimean-Congo Hemorrhagic Fever orthonairovirus. In both cases, free SRO-91 presented no activity on these cell lines.

Keywords: Antitumor; Antiviral; C-nucleoside; Phosphoramidates; Prodrugs; Ribavirin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Cell Line
  • Nucleosides*
  • Prodrugs* / pharmacology
  • Ribavirin / pharmacology

Substances

  • Antiviral Agents
  • Nucleosides
  • Prodrugs
  • Ribavirin