Synthesis and HDAC inhibitory activity of isosteric thiazoline-oxazole largazole analogs

Bioorg Med Chem Lett. 2013 Nov 1;23(21):6025-8. doi: 10.1016/j.bmcl.2013.06.012. Epub 2013 Jun 18.

Abstract

The synthesis of an isosteric analog of the natural product and HDAC inhibitor largazole is described. The sulfur atom in the thizaole ring of the natural product has been replaced with an oxygen atom, constituting an oxazole ring. The biochemical activity and cytotoxicity of this species is described.

Keywords: Conformation; HDAC; Isostere; Largazole; Oxazole.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Depsipeptides / chemical synthesis
  • Depsipeptides / chemistry*
  • Depsipeptides / pharmacology*
  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Molecular Docking Simulation
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Oxazoles / chemical synthesis
  • Oxazoles / chemistry*
  • Oxazoles / pharmacology*
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry*
  • Thiazoles / pharmacology*

Substances

  • Antineoplastic Agents
  • Depsipeptides
  • Histone Deacetylase Inhibitors
  • Oxazoles
  • Thiazoles
  • largazole