Isophthalic Acid-Based HDAC Inhibitors as Potent Inhibitors of HDAC8 from Schistosoma mansoni.
Fiche publication
Date publication
juin 2017
Journal
Archiv der Pharmazie
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ROMIER Christophe
Tous les auteurs :
Stenzel K, Chakrabarti A, Melesina J, Hansen FK, Lancelot J, Herkenhöhner S, Lungerich B, Marek M, Romier C, Pierce RJ, Sippl W, Jung M, Kurz T
Lien Pubmed
Résumé
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.
Mots clés
Docking studies, HDAC8, Histone deacetylase inhibitors, Schistosoma mansoni, Schistosomiasis
Référence
Arch. Pharm. (Weinheim). 2017 Jun;: