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Exploration of thiaheterocyclic hHDAC6 inhibitors as potential antiplasmodial agents

AIM: The recurring resistance of the malaria parasite to many drugs compels the design of innovative chemical entities in antimalarial research. Pan-histone deacetylase inhibitors (pan-HDACis) have recently been presented in the literature as powerful novel antimalarials, although their application...

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Detalles Bibliográficos
Autores principales: Vreese, Rob De, de Kock, Carmen, Smith, Peter J, Chibale, Kelly, D'hooghe, Matthias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Future Science Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099625/
https://www.ncbi.nlm.nih.gov/pubmed/28263085
http://dx.doi.org/10.4155/fmc-2016-0215
Descripción
Sumario:AIM: The recurring resistance of the malaria parasite to many drugs compels the design of innovative chemical entities in antimalarial research. Pan-histone deacetylase inhibitors (pan-HDACis) have recently been presented in the literature as powerful novel antimalarials, although their application is hampered due to toxic side effects. This drawback might be neutralized by the deployment of isoform-selective HDACis. RESULTS: In this study, 42 thiaheterocyclic benzohydroxamic acids, 17 of them being potent and selective hHDAC6 inhibitors, were tested to investigate a possible correlation between hHDAC6 inhibition and antiplasmodial activity. CONCLUSION: Four hHDAC6 inhibitors showed submicromolar potency against both a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodium falciparum with high selectivity indices, pointing to the relevance of exploring hHDAC6 inhibitors as potential new antiplasmodial agents.