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Arch Pharm (Weinheim). 2017 Aug;350(8). doi: 10.1002/ardp.201700096. Epub 2017 Jun 22.

Isophthalic Acid-Based HDAC Inhibitors as Potent Inhibitors of HDAC8 from Schistosoma mansoni.

Author information

1
Institute of Pharmaceutical and Medicinal Chemistry, Heinrich-Heine-University, Düsseldorf, Germany.
2
Institute of Pharmaceutical Sciences, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
3
Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
4
Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Leipzig University, Leipzig, Germany.
5
Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 UMR 8204CIIL - Centre d'Infection et d'Immunité de Lille, Lille, France.
6
IGBMC, Université de Strasbourg, Illkirch, France.

Abstract

Schistosoma mansoni histone deacetylase 8 (SmHDAC8) has been recently identified as a new potential target for the treatment of schistosomiasis. A series of newly designed and synthesized alkoxyamide-based and hydrazide-based HDAC inhibitors were tested for inhibitory activity against SmHDAC8 and human HDACs 1, 6, and 8. The front runner compounds showed submicromolar activity against SmHDAC8 and modest preference for SmHDAC8 over its human orthologue hHDAC8. Docking studies provided insights into the putative binding mode in SmHDAC8 and allowed rationalization of the observed selectivity profile.

KEYWORDS:

Docking studies; HDAC8; Histone deacetylase inhibitors; Schistosoma mansoni; Schistosomiasis

PMID:
28639720
DOI:
10.1002/ardp.201700096
[Indexed for MEDLINE]

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