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

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.

A series of newly designed and synthesized alkoxyamide‐based and hydrazide‐based histone deacetylase (HDAC) inhibitors were tested for inhibitory activity against Schistosoma mansoni HDAC8 and human HDACs 1, 6, and 8. Docking studies provide insights into the putative binding mode in SmHDAC8 and allow rationalization of the observed selectivity profile.

Source: Archiv der Pharmazie - June 1, 2017 Category: Drugs & Pharmacology Authors: Katharina Stenzel, Alokta Chakrabarti, Jelena Melesina, Finn K. Hansen, Julien Lancelot, Simon Herkenh öhner, Beate Lungerich, Martin Marek, Christophe Romier, Raymond. J. Pierce, Wolfgang Sippl, Manfred Jung, Thomas Kurz Tags: Full Paper Source Type: research