Xanthone derivatives as potential inhibitors of miRNA processing by human Dicer: targeting secondary structures of pre-miRNA by small molecules

Bioorg Med Chem Lett. 2013 Jan 1;23(1):252-5. doi: 10.1016/j.bmcl.2012.10.108. Epub 2012 Nov 2.

Abstract

In recent years, various biological processes have been found to be regulated by miRNA-mediated gene silencing. A small molecule that modulate the miRNA pathway will provide the biological tool for elucidating mechanisms of miRNA-mediated gene regulation, and can be the drug lead for miRNA related diseases. In this study, we demonstrated that an aminoalkoxy-substituted thioxanthone derivative interferes Dicer-mediated processing of pre-miRNA. Information about the interaction between these xanthone derivatives and pre-miRNAs will enable us to design and develop new small molecule-based inhibitors for miRNA pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DEAD-box RNA Helicases / antagonists & inhibitors
  • DEAD-box RNA Helicases / metabolism*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism*
  • Humans
  • MicroRNAs / metabolism*
  • Nucleic Acid Conformation
  • Protein Binding
  • RNA Interference
  • Ribonuclease III / antagonists & inhibitors
  • Ribonuclease III / metabolism*
  • Thioxanthenes / chemistry
  • Thioxanthenes / metabolism
  • Xanthones / chemistry
  • Xanthones / metabolism*

Substances

  • Enzyme Inhibitors
  • MicroRNAs
  • Thioxanthenes
  • Xanthones
  • xanthone
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases
  • thioxanthone