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Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites †
Kinetoplastids are the causative agents of leishmaniasis, human African trypanosomiasis, and American trypanosomiasis. They are responsible for high mortality and morbidity in (sub)tropical regions. Adequate treatment options are limited and have several drawbacks, such as toxicity, need for parente...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356981/ https://www.ncbi.nlm.nih.gov/pubmed/32599761 http://dx.doi.org/10.3390/microorganisms8060950 |
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author | Van den Kerkhof, Magali Sterckx, Yann G.-J. Leprohon, Philippe Maes, Louis Caljon, Guy |
author_facet | Van den Kerkhof, Magali Sterckx, Yann G.-J. Leprohon, Philippe Maes, Louis Caljon, Guy |
author_sort | Van den Kerkhof, Magali |
collection | PubMed |
description | Kinetoplastids are the causative agents of leishmaniasis, human African trypanosomiasis, and American trypanosomiasis. They are responsible for high mortality and morbidity in (sub)tropical regions. Adequate treatment options are limited and have several drawbacks, such as toxicity, need for parenteral administration, and occurrence of treatment failure and drug resistance. Therefore, there is an urgency for the development of new drugs. Phenotypic screening already allowed the identification of promising new chemical entities with anti-kinetoplastid activity potential, but knowledge on their mode-of-action (MoA) is lacking due to the generally applied whole-cell based approach. However, identification of the drug target is essential to steer further drug discovery and development. Multiple complementary techniques have indeed been used for MoA elucidation. In this review, the different ‘omics’ approaches employed to define the MoA or mode-of-resistance of current reference drugs and some new anti-kinetoplastid compounds are discussed. |
format | Online Article Text |
id | pubmed-7356981 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73569812020-07-23 Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites † Van den Kerkhof, Magali Sterckx, Yann G.-J. Leprohon, Philippe Maes, Louis Caljon, Guy Microorganisms Review Kinetoplastids are the causative agents of leishmaniasis, human African trypanosomiasis, and American trypanosomiasis. They are responsible for high mortality and morbidity in (sub)tropical regions. Adequate treatment options are limited and have several drawbacks, such as toxicity, need for parenteral administration, and occurrence of treatment failure and drug resistance. Therefore, there is an urgency for the development of new drugs. Phenotypic screening already allowed the identification of promising new chemical entities with anti-kinetoplastid activity potential, but knowledge on their mode-of-action (MoA) is lacking due to the generally applied whole-cell based approach. However, identification of the drug target is essential to steer further drug discovery and development. Multiple complementary techniques have indeed been used for MoA elucidation. In this review, the different ‘omics’ approaches employed to define the MoA or mode-of-resistance of current reference drugs and some new anti-kinetoplastid compounds are discussed. MDPI 2020-06-24 /pmc/articles/PMC7356981/ /pubmed/32599761 http://dx.doi.org/10.3390/microorganisms8060950 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Van den Kerkhof, Magali Sterckx, Yann G.-J. Leprohon, Philippe Maes, Louis Caljon, Guy Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites † |
title | Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites † |
title_full | Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites † |
title_fullStr | Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites † |
title_full_unstemmed | Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites † |
title_short | Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites † |
title_sort | experimental strategies to explore drug action and resistance in kinetoplastid parasites † |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356981/ https://www.ncbi.nlm.nih.gov/pubmed/32599761 http://dx.doi.org/10.3390/microorganisms8060950 |
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