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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Future Science Ltd
2017
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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 |
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author | Vreese, Rob De de Kock, Carmen Smith, Peter J Chibale, Kelly D'hooghe, Matthias |
author_facet | Vreese, Rob De de Kock, Carmen Smith, Peter J Chibale, Kelly D'hooghe, Matthias |
author_sort | Vreese, Rob De |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7099625 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Future Science Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-70996252020-03-27 Exploration of thiaheterocyclic hHDAC6 inhibitors as potential antiplasmodial agents Vreese, Rob De de Kock, Carmen Smith, Peter J Chibale, Kelly D'hooghe, Matthias Future Med Chem Short Communication 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. Future Science Ltd 2017-03 2017-03-06 /pmc/articles/PMC7099625/ /pubmed/28263085 http://dx.doi.org/10.4155/fmc-2016-0215 Text en © 2017 Future Science Ltd This work is licensed under the Creative Commons Attribution 4.0 License (http://creativecommons.org/licenses/by/4.0/) |
spellingShingle | Short Communication Vreese, Rob De de Kock, Carmen Smith, Peter J Chibale, Kelly D'hooghe, Matthias Exploration of thiaheterocyclic hHDAC6 inhibitors as potential antiplasmodial agents |
title | Exploration of thiaheterocyclic hHDAC6 inhibitors as potential antiplasmodial agents |
title_full | Exploration of thiaheterocyclic hHDAC6 inhibitors as potential antiplasmodial agents |
title_fullStr | Exploration of thiaheterocyclic hHDAC6 inhibitors as potential antiplasmodial agents |
title_full_unstemmed | Exploration of thiaheterocyclic hHDAC6 inhibitors as potential antiplasmodial agents |
title_short | Exploration of thiaheterocyclic hHDAC6 inhibitors as potential antiplasmodial agents |
title_sort | exploration of thiaheterocyclic hhdac6 inhibitors as potential antiplasmodial agents |
topic | Short Communication |
url | 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 |
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