The antileishmanial activity of isoforms 6- and 8-selective histone deacetylase inhibitors

Bioorg Med Chem Lett. 2014 Oct 15;24(20):4826-30. doi: 10.1016/j.bmcl.2014.08.060. Epub 2014 Sep 4.

Abstract

Histone deacetylase inhibitors (HDACi) pleiotropy is largely due to their nonselective inhibition of various cellular HDAC isoforms. Connecting inhibition of a specific isoform to biological responses and/or phenotypes is essential toward deconvoluting HDACi pleiotropy. The contribution of classes I and II HDACs to the antileishmanial activity of HDACi was investigated using the amastigote and promastigote forms of Leishmania donovani. We observed that the antileishmanial activities of HDACi are largely due to the inhibition of HDAC6-like activity. This observation could facilitate the development of HDACi as antileishmanial agents.

Keywords: 3-Hydroxypyridin-2-thione; Histone deacetylase inhibitors; Leishmania donovani; Trichostatin A; Tubastatin A.

Publication types

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

MeSH terms

  • Antiprotozoal Agents / chemical synthesis
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / metabolism*
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Leishmania donovani / drug effects*
  • Leishmania donovani / enzymology
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Structure-Activity Relationship

Substances

  • Antiprotozoal Agents
  • Histone Deacetylase Inhibitors
  • Isoenzymes
  • Histone Deacetylases