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.

Chemically Diverse S. mansoni HDAC8 Inhibitors Reduced Viability in Worm Larval and Adult Stages

Noce, Beatrice;Di Bello, Elisabetta;Zwergel, Clemens;Fioravanti, Rossella;Valente, Sergio;Rotili, Dante;Ansari, Mohammad Salik Zeya;Trisciuoglio, Daniela;Mai, Antonello
2022

Abstract

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.
File allegati a questo prodotto
File Dimensione Formato  
Noce_ChemicallyAA_2022.pdf

solo gestori archivio

Tipologia: Documento in Post-print (versione successiva alla peer review e accettata per la pubblicazione)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 1.15 MB
Formato Adobe PDF
1.15 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Noce_Chemically_2022.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 1.37 MB
Formato Adobe PDF
1.37 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1658358
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact