Design, synthesis and biological evaluation of tyrosine-based hydroxamic acid analogs as novel histone deacetylases (HDACs) inhibitors

Bioorg Med Chem. 2011 Aug 1;19(15):4437-44. doi: 10.1016/j.bmc.2011.06.046. Epub 2011 Jun 21.

Abstract

Histone deacetylases (HDACs) are a promising target for treating cancer and some other disorders. Herein, based on the structure of our previously reported tetrahydroisoquinoline-based hydroxamic acids, a novel series of tyrosine-based hydroxamic acid derivatives was designed and synthesized as HDACs inhibitors. Compared with tetrahydroisoquinoline-based hydroxamic acids, tyrosine-based hydroxamic acid derivatives exhibited more potent HDAC8 inhibitory activity. However, the antiproliferative activities and HeLa cell nuclear extract inhibition of several selected tyrosine-based hydroxamic acids were moderate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Survival / drug effects
  • Drug Design*
  • HeLa Cells
  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / metabolism
  • Humans
  • Hydroxamic Acids / chemical synthesis
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / pharmacology
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Repressor Proteins / antagonists & inhibitors*
  • Repressor Proteins / metabolism
  • Structure-Activity Relationship
  • Tyrosine / chemical synthesis
  • Tyrosine / chemistry
  • Tyrosine / pharmacology

Substances

  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Repressor Proteins
  • Tyrosine
  • HDAC8 protein, human
  • Histone Deacetylases