Hydroxamic acid based histone deacetylase inhibitors with confirmed activity against the malaria parasite.

Abstract:

:Recent studies have highlighted a key role in regulating gene transcription, in both eukaryotes and prokaryotes, by enzymes that control the acetylation and deacetylation of histones. In particular, inhibitors of histone deacetylases (HDAC-Is) have been shown effective in controlling the development of many parasites, such as the plasmodium of malaria. Here we report the results of a study aimed at evaluating antiparasitic effect of two classes of HDAC-Is bearing different zinc binding group (hydroxamic acid vs thiol). The study showed that only the hydroxamic acid based HDAC inhibitors were active, with Plasmodium falciparum being the most sensitive parasite, having from low double-digit to single-digit nanomolar range in vitro activities. Among three derivatives evaluated also in vivo, ST8086AA1 (8) effectively inhibited 88% of the development of Plasmodium falciparum.

journal_name

Bioorg Med Chem Lett

authors

Giannini G,Battistuzzi G,Vignola D

doi

10.1016/j.bmcl.2014.12.051

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

459-61

issue

3

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(14)01359-6

journal_volume

25

pub_type

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