Synthesis of benzothiophene-based hydroxamic acids as potent and selective HDAC6 inhibitors

Chem Commun (Camb). 2015 Jun 18;51(48):9868-71. doi: 10.1039/c5cc03295d.

Abstract

A small library of 3-[(4-hydroxycarbamoylphenyl)aminomethyl]benzothiophenes was prepared and assessed as a novel class of HDAC6 inhibitors, leading to the identification of three representatives as potent and selective HDAC6 inhibitors. Further tests with regard to inflammatory responses indicated that HDAC6 inhibition can be uncoupled from transcriptional inhibition at the level of activated NF-κB, AP-1, and GR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Histone Deacetylase 6
  • Histone Deacetylase Inhibitors / chemical synthesis*
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism
  • Humans
  • Hydroxamic Acids / chemical synthesis*
  • Hydroxamic Acids / chemistry
  • Models, Molecular
  • NF-kappa B / metabolism
  • Thiophenes / chemical synthesis*
  • Thiophenes / chemistry
  • Transcription Factor AP-1 / metabolism
  • Tubulin / metabolism

Substances

  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • NF-kappa B
  • Thiophenes
  • Transcription Factor AP-1
  • Tubulin
  • benzothiophene
  • HDAC6 protein, human
  • Histone Deacetylase 6
  • Histone Deacetylases