Fiche publication
Date publication
octobre 2025
Journal
ACS infectious diseases
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ROMIER Christophe
Tous les auteurs :
Gimmelli R, Papoff G, Fabbrizi E, Guida M, Lalli C, Saccoccia F, Häberli C, Keiser J, Monaldi D, Jung M, Romier C, Rotili D, Mai A, Ruberti G
Lien Pubmed
Résumé
Schistosomiasis, a neglected tropical disease caused by trematodes of genus, urgently requires new treatments due to praziquantel's limited efficacy against juvenile worms as well as the threat of drug resistance. In this study, we evaluated a series of benzodeazaoxaflavin (BDF4)-based compounds as inhibitors of the parasite's epigenetic enzyme Sirt2. Three compounds, - (MC2346, MC2141, and MC2345), showed activity against both Liberian and Puerto Rican strains of . The compounds reduced schistosomula and adult worm pair viability, pairing, and egg production, with low cytotoxicity in mammalian cells. These effects were linked to histone H3 hyperacetylation and cytochrome c-mediated apoptosis, confirming Sirt2 as a functional target. These findings support the development of Sirt2 inhibitors as novel antischistosomal agents with therapeutic potential for both curative and preventive applications. Further studies are warranted to assess their pharmacokinetic and safety profiles.
Mots clés
Schistosoma mansoni, SmSirt2 inhibitors, phenotypic and biochemical characterization, sirtuins
Référence
ACS Infect Dis. 2025 10 7;:
