Anticancer Ruthenium Complexes with HDAC Isoform Selectivity

Molecules. 2020 May 21;25(10):2383. doi: 10.3390/molecules25102383.

Abstract

The histone deacetylase (HDAC) enzymes have emerged as an important class of molecular targets in cancer therapy, with five inhibitors in clinical use. Recently, it has been shown that a lack of selectivity between the 11 Zn-dependent HDAC isoforms may lead to unwanted side-effects. In this paper, we show that piano stool Ru complexes can act as HDAC inhibitors, and variation in the capping arene leads to differences in HDAC isoform selectivity.

Keywords: histone deacetylase inhibitors; ruthenium in medicine; selective enzyme inhibition.

MeSH terms

  • Cell Proliferation / drug effects*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • HeLa Cells
  • Histone Deacetylase 1 / antagonists & inhibitors
  • Histone Deacetylase 1 / genetics
  • Histone Deacetylase 1 / ultrastructure
  • Histone Deacetylase 6 / antagonists & inhibitors
  • Histone Deacetylase 6 / genetics
  • Histone Deacetylase 6 / ultrastructure
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Protein Conformation / drug effects
  • Protein Isoforms / genetics
  • Ruthenium / chemistry
  • Ruthenium / pharmacology
  • Ruthenium Compounds / chemistry
  • Ruthenium Compounds / pharmacology*

Substances

  • Coordination Complexes
  • Histone Deacetylase Inhibitors
  • Protein Isoforms
  • Ruthenium Compounds
  • Ruthenium
  • HDAC1 protein, human
  • HDAC6 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylase 6