Schistosomiasis is a major neglected parasitic disease that affects more than 240 million people worldwide and for which the control strategy consists of mass treatment with the only available drug, praziquantel. Schistosomes display morphologically distinct stages during their life cycle and the transformations between stages are controlled by epigenetic mechanisms. The targeting of epigenetic actors might therefore represent the parasites' Achilles' heel. Specifically, histone deacetylases have been recently characterized as drug targets for the treatment of schistosomiasis. This review focuses on the recent development of inhibitors for schistosome histone deacetylases. In particular, advances in the development of inhibitors of histone deacetylase 8 have indicated that targeting this enzyme is a promising approach for the treatment of this infection.
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http://dx.doi.org/10.3390/ph15010080 | DOI Listing |
J Med Chem
January 2025
Department of Pharmaceutical and Cell Biological Chemistry, Pharmaceutical Institute, University of Bonn institution, An der Immenburg 4, Bonn 53121, Germany.
Targeted protein degradation (TPD) represents a promising alternative to conventional occupancy-driven protein inhibition. Despite the existence of more than 600 E3 ligases in the human proteome, so far only a few have been utilized for TPD of histone deacetylases (HDACs), which represent important epigenetic anticancer drug targets. In this study, we disclose the first-in-class Fem-1 homologue B (FEM1B)-recruiting HDAC degraders.
View Article and Find Full Text PDFOrganoselenocyanates have attracted considerable attention in recent years due to their therapeutic potential and versatility in medicinal chemistry. Here, we report on the mechanism of inhibition by 5-phenylcarbamoylpentyl selenocyanide (SelSA-2), an analogue of the well-characterized histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA, a.k.
View Article and Find Full Text PDFThe cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction.
View Article and Find Full Text PDFJAAD Case Rep
January 2025
Department of Dermatology, Columbia University Irving Medical Center, New York, New York.
FEMS Microbes
December 2024
FG16: Mycotic and Parasitic Agents and Mycobacteria, Robert Koch Institute, 13353 Berlin, Germany.
The apicomplexan parasite has a complex life cycle. Access to sexual stages and sporozoite-containing oocysts, essential for studying the parasite's environmental transmission, is limited and requires animal experiments with cats. Thus, alternatives and resource-efficient methods are needed.
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