Bioorg Med Chem Lett. 2015 Feb 1;25(3):459-61. doi: 10.1016/j.bmcl.2014.12.051.

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

Giannini G1, Battistuzzi G2, Vignola D2.
  • 1R&D Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., Via Pontina Km 30,400, I-00040 Pomezia, Roma, Italy. Electronic address: giuseppe.giannini@sigma-tau.it.
  • 2R&D Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., Via Pontina Km 30,400, I-00040 Pomezia, Roma, Italy.

 

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.

KEYWORDS: Antimalarial activity; Antiprotozoan drug; HDAC inhibitors; Hydroxamic acid; Plasmodium falciparum

PMID: 25563890

 

 

2015. AACR - Giuseppe Giannini

Contact:

Dr. Giuseppe Giannini

Head of Medicinal Chemistry; Project Leader

Tel. +39 06 9139.3640. Fax. +39 06 9139.4267.

Email: giuseppe.giannini@sigma-tau.it

 

 

 

 

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