Isoxazole-containing 5' mRNA cap analogues as inhibitors of the translation initiation process

Bioorg Chem. 2020 Mar:96:103583. doi: 10.1016/j.bioorg.2020.103583. Epub 2020 Jan 13.

Abstract

Herein we describe a synthesis of new isoxazole-containing 5' mRNA cap analogues via a cycloaddition reaction. The obtained analogues show a capability to inhibit cap-dependent translation in vitro and are characterized by a new binding mode in which an isoxazolic ring, instead of guanine, is involved in the stacking effect. Our study provides valuable information toward designing new compounds that can be potentially used as anticancer therapeutics.

Keywords: Cap analogue; Cycloaddition reaction; Isoxazol; Translation initiation; mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Design
  • Eukaryotic Initiation Factor-4E / metabolism
  • Isoxazoles / chemical synthesis
  • Isoxazoles / chemistry*
  • Isoxazoles / pharmacology*
  • Mice
  • Molecular Docking Simulation
  • Peptide Chain Initiation, Translational / drug effects*
  • RNA Cap Analogs / chemical synthesis
  • RNA Cap Analogs / chemistry*
  • RNA Cap Analogs / pharmacology*
  • Rabbits

Substances

  • Eukaryotic Initiation Factor-4E
  • Isoxazoles
  • RNA Cap Analogs