Apicidin: A novel antiprotozoal agent that inhibits parasite histone deacetylase Academic Article uri icon

Overview

MeSH Major

  • Antiprotozoal Agents
  • Enzyme Inhibitors
  • Eukaryota
  • Histone Deacetylase Inhibitors
  • Malaria
  • Peptides, Cyclic
  • Plasmodium berghei

abstract

  • A novel fungal metabolite, apicidin [cyclo(N-O-methyl-L-tryptophanyl-L -isoleucinyl-D-pipecolinyl-L-2-amino-8-oxodecanoyl)], that exhibits potent, broad spectrum antiprotozoal activity in vitro against Apicomplexan parasites has been identified. It is also orally and parenterally active in vivo against Plasmodium berghei malaria in mice. Many Apicomplexan parasites cause serious, life-threatening human and animal diseases, such as malaria, cryptosporidiosis, toxoplasmosis, and coccidiosis, and new therapeutic agents are urgently needed. Apicidin's antiparasitic activity appears to be due to low nanomolar inhibition of Apicomplexan histone deacetylase (HDA), which induces hyperacetylation of histones in treated parasites. The acetylation-deacetylation of histones is a thought to play a central role in transcriptional control in eukaryotic cells. Other known HDA inhibitors were also evaluated and found to possess antiparasitic activity, suggesting that HDA is an attractive target for the development of novel antiparasitic agents.

publication date

  • November 12, 1996

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC24060

Digital Object Identifier (DOI)

  • 10.1073/pnas.93.23.13143

PubMed ID

  • 8917558

Additional Document Info

start page

  • 13143

end page

  • 7

volume

  • 93

number

  • 23