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Screening a Natural Product-Based Library against Kinetoplastid Parasites

Kinetoplastid parasites cause vector-borne parasitic diseases including leishmaniasis, human African trypanosomiasis (HAT) and Chagas disease. These Neglected Tropical Diseases (NTDs) impact on some of the world’s lowest socioeconomic communities. Current treatments for these diseases cause severe t...

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Autores principales: Zulfiqar, Bilal, Jones, Amy J., Sykes, Melissa L., Shelper, Todd B., Davis, Rohan A., Avery, Vicky M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151456/
https://www.ncbi.nlm.nih.gov/pubmed/29023425
http://dx.doi.org/10.3390/molecules22101715
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author Zulfiqar, Bilal
Jones, Amy J.
Sykes, Melissa L.
Shelper, Todd B.
Davis, Rohan A.
Avery, Vicky M.
author_facet Zulfiqar, Bilal
Jones, Amy J.
Sykes, Melissa L.
Shelper, Todd B.
Davis, Rohan A.
Avery, Vicky M.
author_sort Zulfiqar, Bilal
collection PubMed
description Kinetoplastid parasites cause vector-borne parasitic diseases including leishmaniasis, human African trypanosomiasis (HAT) and Chagas disease. These Neglected Tropical Diseases (NTDs) impact on some of the world’s lowest socioeconomic communities. Current treatments for these diseases cause severe toxicity and have limited efficacy, highlighting the need to identify new treatments. In this study, the Davis open access natural product-based library was screened against kinetoplastids (Leishmania donovani DD8, Trypanosoma brucei brucei and Trypanosoma cruzi) using phenotypic assays. The aim of this study was to identify hit compounds, with a focus on improved efficacy, selectivity and potential to target several kinetoplastid parasites. The IC(50) values of the natural products were obtained for L. donovani DD8, T. b. brucei and T. cruzi in addition to cytotoxicity against the mammalian cell lines, HEK-293, 3T3 and THP-1 cell lines were determined to ascertain parasite selectivity. Thirty-one compounds were identified with IC(50) values of ≤10 µM against the kinetoplastid parasites tested. Lissoclinotoxin E (1) was the only compound identified with activity across all three investigated parasites, exhibiting IC(50) values <5 µM. In this study, natural products with the potential to be new chemical starting points for drug discovery efforts for kinetoplastid diseases were identified.
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spelling pubmed-61514562018-11-13 Screening a Natural Product-Based Library against Kinetoplastid Parasites Zulfiqar, Bilal Jones, Amy J. Sykes, Melissa L. Shelper, Todd B. Davis, Rohan A. Avery, Vicky M. Molecules Article Kinetoplastid parasites cause vector-borne parasitic diseases including leishmaniasis, human African trypanosomiasis (HAT) and Chagas disease. These Neglected Tropical Diseases (NTDs) impact on some of the world’s lowest socioeconomic communities. Current treatments for these diseases cause severe toxicity and have limited efficacy, highlighting the need to identify new treatments. In this study, the Davis open access natural product-based library was screened against kinetoplastids (Leishmania donovani DD8, Trypanosoma brucei brucei and Trypanosoma cruzi) using phenotypic assays. The aim of this study was to identify hit compounds, with a focus on improved efficacy, selectivity and potential to target several kinetoplastid parasites. The IC(50) values of the natural products were obtained for L. donovani DD8, T. b. brucei and T. cruzi in addition to cytotoxicity against the mammalian cell lines, HEK-293, 3T3 and THP-1 cell lines were determined to ascertain parasite selectivity. Thirty-one compounds were identified with IC(50) values of ≤10 µM against the kinetoplastid parasites tested. Lissoclinotoxin E (1) was the only compound identified with activity across all three investigated parasites, exhibiting IC(50) values <5 µM. In this study, natural products with the potential to be new chemical starting points for drug discovery efforts for kinetoplastid diseases were identified. MDPI 2017-10-12 /pmc/articles/PMC6151456/ /pubmed/29023425 http://dx.doi.org/10.3390/molecules22101715 Text en © 2017 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 Article
Zulfiqar, Bilal
Jones, Amy J.
Sykes, Melissa L.
Shelper, Todd B.
Davis, Rohan A.
Avery, Vicky M.
Screening a Natural Product-Based Library against Kinetoplastid Parasites
title Screening a Natural Product-Based Library against Kinetoplastid Parasites
title_full Screening a Natural Product-Based Library against Kinetoplastid Parasites
title_fullStr Screening a Natural Product-Based Library against Kinetoplastid Parasites
title_full_unstemmed Screening a Natural Product-Based Library against Kinetoplastid Parasites
title_short Screening a Natural Product-Based Library against Kinetoplastid Parasites
title_sort screening a natural product-based library against kinetoplastid parasites
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151456/
https://www.ncbi.nlm.nih.gov/pubmed/29023425
http://dx.doi.org/10.3390/molecules22101715
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