Fiche publication
Date publication
octobre 2022
Journal
ChemMedChem
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ROMIER Christophe
Tous les auteurs :
Noce B, Di Bello E, Zwergel C, Fioravanti R, Valente S, Rotili D, Masotti A, Ansari MSZ, Trisciuoglio D, Chakrabarti A, Romier C, Robaa D, Sippl W, Jung M, Häberli C, Keiser J, Mai A
Lien Pubmed
Résumé
Schistosoma mansoni HDAC8 is a reliable target to fight schistosomiasis, and several inhibitors have been reported in the literature up to now. Nevertheless, only a few displayed selectivity over the human deacetylases and some exhibited very low or no activity against parasite larvae and/or adult worms. We report here the in vitro enzyme and biological activity of a small library of HDAC inhibitors from our lab, in many cases exhibiting submicromolar/nanomolar potency against smHDAC8 and diverse degrees of selectivity over hHDAC1 and/or hHDAC6. Such compounds were tested against schistosomula, and a selection of them against the adult forms of S. mansoni, to detect their effect on viability. Some of them showed the highest viability reduction for the larval stage with IC50 values around 1 µM and/or displayed ~ 40-50% activity in adult worms at 10 µM, joined to moderate to no toxicity in human fibroblast MRC-5 cells.
Mots clés
S. mansoni, epigenetic drugs, histone deacetylase inhibitors, neglected parasitic diseases, newly transformed schistosomula
Référence
ChemMedChem. 2022 10 17;:
