Design and synthesis of thiazole-5-hydroxamic acids as novel histone deacetylase inhibitors

Bioorg Med Chem Lett. 2007 Nov 1;17(21):5995-9. doi: 10.1016/j.bmcl.2007.07.050. Epub 2007 Aug 19.

Abstract

We have designed and synthesized a series of structurally novel hydroxamic acid-based histone deacetylase (HDAC) inhibitors characterized by a zinc chelating head group attached directly to a thiazole ring. The thiazole ring connects to a piperazine spacer, which is capped with a sulfonamide group. These novel molecules potently inhibit an HDAC enzyme mixture derived from HeLa cervical carcinoma cells and show potent antiproliferative activity against the breast cancer cell line MCF7.

MeSH terms

  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • HeLa Cells
  • Histone Deacetylase Inhibitors*
  • Humans
  • Hydroxamic Acids / chemical synthesis
  • Hydroxamic Acids / chemistry*
  • Hydroxamic Acids / pharmacology*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids