Minor structural modifications to Pracinostat produce big changes in its biological responses

Chem Biol Drug Des. 2019 Aug;94(2):1488-1493. doi: 10.1111/cbdd.13527. Epub 2019 Apr 29.

Abstract

A series of compounds similar to Pracinostat that contained benzimidazole ring and N-hydroxyacrylamide attached at 5- or 6-position were designed, synthesized, and evaluated as HDAC inhibitors. It was interesting to find that the corresponding derivative 1 with N-hydroxyacrylamide attached at 5-position was a potent HDAC inhibitor while the others at 6-position were not. This is the first time to demonstrate the position difference plays important role in the HDAC inhibitory activities of the cinnamic hydroxamates.

Keywords: HDAC inhibitors; Pracinostat; histone deacetylases; hydroxamic acids; synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzimidazoles* / chemistry
  • Benzimidazoles* / pharmacology
  • HeLa Cells
  • Histone Deacetylase 6 / antagonists & inhibitors
  • Histone Deacetylase 6 / metabolism
  • Histone Deacetylase Inhibitors* / chemistry
  • Histone Deacetylase Inhibitors* / pharmacology
  • Humans

Substances

  • Benzimidazoles
  • Histone Deacetylase Inhibitors
  • SB939 compound
  • HDAC6 protein, human
  • Histone Deacetylase 6