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Article Dans Une Revue Antimicrobial Agents and Chemotherapy Année : 2023

Hydroxamate-based compounds are potent inhibitors of Toxoplasma gondii HDAC biological activity

Tom Boissavy
  • Fonction : Auteur
Dante Rotili
  • Fonction : Auteur
Thomas Mouveaux
  • Fonction : Auteur
Emmanuel Roger
  • Fonction : Auteur
El Moukthar Aliouat
  • Fonction : Auteur
Christine Pierrot
  • Fonction : Auteur
Sergio Valente
  • Fonction : Auteur
Antonello Mai
  • Fonction : Auteur

Résumé

ABSTRACT Toxoplasmosis is a critical health issue for immune-deficient individuals and the offspring of newly infected mothers. It is caused by a unicellular intracellular parasite called Toxoplasma gondii that is found worldwide. Although efficient drugs are commonly used to treat toxoplasmosis, serious adverse events are common. Therefore, new compounds with potent anti- T . gondii activity are needed to provide better suited treatments. We have tested compounds designed to target specifically histone deacetylase enzymes. Among the 55 compounds tested, we identified three compounds showing a concentration of drug required for 50% inhibition (IC 50 ) in the low 100 nM range with a selectivity index of more than 100. These compounds are not only active at inhibiting the growth of the parasite in vitro but also at preventing some of the consequences of the acute disease in vivo . Two of these hydroxamate based compound also induce a hyper-acetylation of the parasite histones while the parasitic acetylated tubulin level remains unchanged. These findings suggest that the enzymes regulating histone acetylation are potent therapeutic targets for the treatment of acute toxoplasmosis.
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Dates et versions

hal-04252830 , version 1 (21-10-2023)

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Tom Boissavy, Dante Rotili, Thomas Mouveaux, Emmanuel Roger, El Moukthar Aliouat, et al.. Hydroxamate-based compounds are potent inhibitors of Toxoplasma gondii HDAC biological activity. Antimicrobial Agents and Chemotherapy, inPress, ⟨10.1128/aac.00661-23⟩. ⟨hal-04252830⟩
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