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Isophthalic Acid‐Based HDAC Inhibitors as Potent Inhibitors of HDAC8 from Schistosoma mansoni
Author(s) -
Stenzel Katharina,
Chakrabarti Alokta,
Melesina Jelena,
Hansen Finn K.,
Lancelot Julien,
Herkenhöhner Simon,
Lungerich Beate,
Marek Martin,
Romier Christophe,
Pierce Raymond. J.,
Sippl Wolfgang,
Jung Manfred,
Kurz Thomas
Publication year - 2017
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201700096
Subject(s) - schistosoma mansoni , hdac8 , chemistry , histone deacetylase , docking (animal) , biochemistry , hydrazide , stereochemistry , histone , biology , schistosomiasis , medicine , immunology , organic chemistry , nursing , gene , helminths
Schistosoma mansoni histone deacetylase 8 ( Sm HDAC8) 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 Sm HDAC8 and human HDACs 1, 6, and 8. The front runner compounds showed submicromolar activity against Sm HDAC8 and modest preference for Sm HDAC8 over its human orthologue hHDAC8. Docking studies provided insights into the putative binding mode in Sm HDAC8 and allowed rationalization of the observed selectivity profile.