Drugging the schistosome zinc-dependent HDACs: current progress and future perspectives

Future Med Chem. 2015;7(6):783-800. doi: 10.4155/fmc.15.25.


Schistosomes, like many eukaryotic pathogens, typically display morphologically distinct stages during their life cycles. Epigenetic mechanisms underlie the pathogens' morphological transformations, and the targeting of epigenetics-driven cellular programs therefore represents an Achilles' heel of parasites. To speed up the search for new antiparasitic agents, drugs validated for other diseases can be rationally optimized into antiparasitic therapeutics. Specifically, zinc-dependent histone deacetylases (HDACs) are the most explored targets for epigenetic therapies, notably for anticancer treatments. This review focuses on the development of drug-leads inhibiting HDACs from schistosomes. More precisely, current progress on Schistosoma mansoni HDAC8 (smHDAC8) provided a proof of concept that targeting epigenetic enzymes is a valid approach to treat diseases caused by schistosomes, and possibly other eukaryotic pathogens.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anthelmintics / chemistry
  • Anthelmintics / pharmacology*
  • Drug Discovery / methods*
  • Helminth Proteins / antagonists & inhibitors
  • Helminth Proteins / chemistry
  • Helminth Proteins / metabolism*
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Targeted Therapy / methods
  • Schistosoma / chemistry
  • Schistosoma / drug effects*
  • Schistosoma / metabolism
  • Schistosoma mansoni / chemistry
  • Schistosoma mansoni / drug effects
  • Schistosoma mansoni / metabolism
  • Schistosomiasis / drug therapy*
  • Schistosomiasis / parasitology
  • Sequence Alignment
  • Zinc / metabolism


  • Anthelmintics
  • Helminth Proteins
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases
  • Zinc