Mercaptoamide-based non-hydroxamic acid type histone deacetylase inhibitors

Bioorg Med Chem Lett. 2005 Apr 15;15(8):1969-72. doi: 10.1016/j.bmcl.2005.02.075.

Abstract

Inhibitors of histone deacetylases (HDAC) are emerging as a promising class of anti-cancer agents. A mercaptoamide functionality was designed as a bidentate zinc chelator and incorporated into the hydroxamic acid based SAHA (1) scaffold in order to identify non-hydroxamate compounds as potential inhibitors of histone deacetylases. Two sets of mercaptoamides 2 and 3 with varying spacer length were synthesized and their HDAC inhibitory activity was evaluated. Low micromolar inhibition was observed for mercaptoamides 2e, 3b, and 3d.

MeSH terms

  • Amides / chemistry*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / classification*
  • Enzyme Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors*
  • Hydroxamic Acids / chemistry
  • Sulfhydryl Compounds / chemistry*

Substances

  • Amides
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Sulfhydryl Compounds