Activity in vivo of anti-Trypanosoma cruzi compounds selected from a high throughput screening.
Novel technologies that include recombinant pathogens and rapid detection methods are contributing to the development of drugs for neglected diseases. Recently, the results from the first high throughput screening (HTS) to test compounds for activity against Trypanosoma cruzi trypomastigote infectio...
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ftdoajarticles:oai:doaj.org/article:8ed15afd6eb547c095829922c616d959 2023-05-15T15:11:14+02:00 Activity in vivo of anti-Trypanosoma cruzi compounds selected from a high throughput screening. Grasiella Andriani Anne-Danielle C Chessler Gilles Courtemanche Barbara A Burleigh Ana Rodriguez 2011-08-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001298 https://doaj.org/article/8ed15afd6eb547c095829922c616d959 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3166044?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001298 https://doaj.org/article/8ed15afd6eb547c095829922c616d959 PLoS Neglected Tropical Diseases, Vol 5, Iss 8, p e1298 (2011) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2011 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001298 2022-12-30T21:04:27Z Novel technologies that include recombinant pathogens and rapid detection methods are contributing to the development of drugs for neglected diseases. Recently, the results from the first high throughput screening (HTS) to test compounds for activity against Trypanosoma cruzi trypomastigote infection of host cells were reported. We have selected 23 compounds from the hits of this HTS, which were reported to have high anti-trypanosomal activity and low toxicity to host cells. These compounds were highly purified and their structures confirmed by HPLC/mass spectrometry. The compounds were tested in vitro, where about half of them confirmed the anti-T. cruzi activity reported in the HTS, with IC50 values lower than 5 µM. We have also adapted a rapid assay to test anti-T. cruzi compounds in vivo using mice infected with transgenic T. cruzi expressing luciferase as a model for acute infection. The compounds that were active in vitro were also tested in vivo using this assay, where we found two related compounds with a similar structure and low in vitro IC50 values (0.11 and 0.07 µM) that reduce T. cruzi infection in the mouse model more than 90% after five days of treatment. Our findings evidence the benefits of novel technologies, such as HTS, for the drug discovery pathway of neglected diseases, but also caution about the need to confirm the results in vitro. We also show how rapid methods of in vivo screening based in luciferase-expressing parasites can be very useful to prioritize compounds early in the chain of development. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 5 8 e1298 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Grasiella Andriani Anne-Danielle C Chessler Gilles Courtemanche Barbara A Burleigh Ana Rodriguez Activity in vivo of anti-Trypanosoma cruzi compounds selected from a high throughput screening. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Novel technologies that include recombinant pathogens and rapid detection methods are contributing to the development of drugs for neglected diseases. Recently, the results from the first high throughput screening (HTS) to test compounds for activity against Trypanosoma cruzi trypomastigote infection of host cells were reported. We have selected 23 compounds from the hits of this HTS, which were reported to have high anti-trypanosomal activity and low toxicity to host cells. These compounds were highly purified and their structures confirmed by HPLC/mass spectrometry. The compounds were tested in vitro, where about half of them confirmed the anti-T. cruzi activity reported in the HTS, with IC50 values lower than 5 µM. We have also adapted a rapid assay to test anti-T. cruzi compounds in vivo using mice infected with transgenic T. cruzi expressing luciferase as a model for acute infection. The compounds that were active in vitro were also tested in vivo using this assay, where we found two related compounds with a similar structure and low in vitro IC50 values (0.11 and 0.07 µM) that reduce T. cruzi infection in the mouse model more than 90% after five days of treatment. Our findings evidence the benefits of novel technologies, such as HTS, for the drug discovery pathway of neglected diseases, but also caution about the need to confirm the results in vitro. We also show how rapid methods of in vivo screening based in luciferase-expressing parasites can be very useful to prioritize compounds early in the chain of development. |
format |
Article in Journal/Newspaper |
author |
Grasiella Andriani Anne-Danielle C Chessler Gilles Courtemanche Barbara A Burleigh Ana Rodriguez |
author_facet |
Grasiella Andriani Anne-Danielle C Chessler Gilles Courtemanche Barbara A Burleigh Ana Rodriguez |
author_sort |
Grasiella Andriani |
title |
Activity in vivo of anti-Trypanosoma cruzi compounds selected from a high throughput screening. |
title_short |
Activity in vivo of anti-Trypanosoma cruzi compounds selected from a high throughput screening. |
title_full |
Activity in vivo of anti-Trypanosoma cruzi compounds selected from a high throughput screening. |
title_fullStr |
Activity in vivo of anti-Trypanosoma cruzi compounds selected from a high throughput screening. |
title_full_unstemmed |
Activity in vivo of anti-Trypanosoma cruzi compounds selected from a high throughput screening. |
title_sort |
activity in vivo of anti-trypanosoma cruzi compounds selected from a high throughput screening. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doi.org/10.1371/journal.pntd.0001298 https://doaj.org/article/8ed15afd6eb547c095829922c616d959 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 5, Iss 8, p e1298 (2011) |
op_relation |
http://europepmc.org/articles/PMC3166044?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001298 https://doaj.org/article/8ed15afd6eb547c095829922c616d959 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001298 |
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PLoS Neglected Tropical Diseases |
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5 |
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8 |
container_start_page |
e1298 |
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