In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 93, No. 23 ( 1996-11-12), p. 13143-13147
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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.93.23.13143
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1996
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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