Chemically Diverse S. mansoni HDAC8 Inhibitors Reduce Viability in Worm Larval and Adult Stages - Archive ouverte HAL Access content directly
Journal Articles ChemMedChem Year : 2023

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

Beatrice Noce
  • Function : Author
Elisabetta Di Bello
  • Function : Author
Clemens Zwergel
  • Function : Author
Rossella Fioravanti
  • Function : Author
Sergio Valente
  • Function : Author
Dante Rotili
  • Function : Author
Andrea Masotti
  • Function : Author
Mohammad Salik Zeya Ansari
  • Function : Author
Daniela Trisciuoglio
  • Function : Author
Alokta Chakrabarti
  • Function : Author
Dina Robaa
  • Function : Author
Wolfgang Sippl
  • Function : Author
Manfred Jung
  • Function : Author
Cécile Häberli
  • Function : Author
Jennifer Keiser
  • Function : Author
Antonello Mai
  • Function : Author

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.
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Dates and versions

hal-04219183 , version 1 (26-09-2023)

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Beatrice Noce, Elisabetta Di Bello, Clemens Zwergel, Rossella Fioravanti, Sergio Valente, et al.. Chemically Diverse S. mansoni HDAC8 Inhibitors Reduce Viability in Worm Larval and Adult Stages. ChemMedChem, 2023, 18 (3), ⟨10.1002/cmdc.202200510⟩. ⟨hal-04219183⟩
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