A screen against Leishmania intracellular amastigotes: comparison to a promastigote screen and identification of a host cell-specific hit.
The ability to screen compounds in a high-throughput manner is essential in the process of small molecule drug discovery. Critical to the success of screening strategies is the proper design of the assay, often implying a compromise between ease/speed and a biologically relevant setting. Leishmanias...
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ftdoajarticles:oai:doaj.org/article:6613cfa0133b45b99845a0f1b17c6da1 2023-05-15T15:08:09+02:00 A screen against Leishmania intracellular amastigotes: comparison to a promastigote screen and identification of a host cell-specific hit. Geraldine De Muylder Kenny K H Ang Steven Chen Michelle R Arkin Juan C Engel James H McKerrow 2011-07-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001253 https://doaj.org/article/6613cfa0133b45b99845a0f1b17c6da1 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3139667?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001253 https://doaj.org/article/6613cfa0133b45b99845a0f1b17c6da1 PLoS Neglected Tropical Diseases, Vol 5, Iss 7, p e1253 (2011) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2011 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001253 2022-12-31T01:32:59Z The ability to screen compounds in a high-throughput manner is essential in the process of small molecule drug discovery. Critical to the success of screening strategies is the proper design of the assay, often implying a compromise between ease/speed and a biologically relevant setting. Leishmaniasis is a major neglected disease with limited therapeutic options. In order to streamline efforts for the design of productive drug screens against Leishmania, we compared the efficiency of two screening methods, one targeting the free living and easily cultured promastigote (insect-infective) stage, the other targeting the clinically relevant but more difficult to culture intra-macrophage amastigote (mammal-infective) stage. Screening of a 909-member library of bioactive compounds against Leishmania donovani revealed 59 hits in the promastigote primary screen and 27 in the intracellular amastigote screen, with 26 hits shared by both screens. This suggested that screening against the promastigote stage, although more suitable for automation, fails to identify all active compounds and leads to numerous false positive hits. Of particular interest was the identification of one compound specific to the infective amastigote stage of the parasite. This compound affects intracellular but not axenic parasites, suggesting a host cell-dependent mechanism of action, opening new avenues for anti-leishmanial chemotherapy. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 5 7 e1253 |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Geraldine De Muylder Kenny K H Ang Steven Chen Michelle R Arkin Juan C Engel James H McKerrow A screen against Leishmania intracellular amastigotes: comparison to a promastigote screen and identification of a host cell-specific hit. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
The ability to screen compounds in a high-throughput manner is essential in the process of small molecule drug discovery. Critical to the success of screening strategies is the proper design of the assay, often implying a compromise between ease/speed and a biologically relevant setting. Leishmaniasis is a major neglected disease with limited therapeutic options. In order to streamline efforts for the design of productive drug screens against Leishmania, we compared the efficiency of two screening methods, one targeting the free living and easily cultured promastigote (insect-infective) stage, the other targeting the clinically relevant but more difficult to culture intra-macrophage amastigote (mammal-infective) stage. Screening of a 909-member library of bioactive compounds against Leishmania donovani revealed 59 hits in the promastigote primary screen and 27 in the intracellular amastigote screen, with 26 hits shared by both screens. This suggested that screening against the promastigote stage, although more suitable for automation, fails to identify all active compounds and leads to numerous false positive hits. Of particular interest was the identification of one compound specific to the infective amastigote stage of the parasite. This compound affects intracellular but not axenic parasites, suggesting a host cell-dependent mechanism of action, opening new avenues for anti-leishmanial chemotherapy. |
format |
Article in Journal/Newspaper |
author |
Geraldine De Muylder Kenny K H Ang Steven Chen Michelle R Arkin Juan C Engel James H McKerrow |
author_facet |
Geraldine De Muylder Kenny K H Ang Steven Chen Michelle R Arkin Juan C Engel James H McKerrow |
author_sort |
Geraldine De Muylder |
title |
A screen against Leishmania intracellular amastigotes: comparison to a promastigote screen and identification of a host cell-specific hit. |
title_short |
A screen against Leishmania intracellular amastigotes: comparison to a promastigote screen and identification of a host cell-specific hit. |
title_full |
A screen against Leishmania intracellular amastigotes: comparison to a promastigote screen and identification of a host cell-specific hit. |
title_fullStr |
A screen against Leishmania intracellular amastigotes: comparison to a promastigote screen and identification of a host cell-specific hit. |
title_full_unstemmed |
A screen against Leishmania intracellular amastigotes: comparison to a promastigote screen and identification of a host cell-specific hit. |
title_sort |
screen against leishmania intracellular amastigotes: comparison to a promastigote screen and identification of a host cell-specific hit. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doi.org/10.1371/journal.pntd.0001253 https://doaj.org/article/6613cfa0133b45b99845a0f1b17c6da1 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 5, Iss 7, p e1253 (2011) |
op_relation |
http://europepmc.org/articles/PMC3139667?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001253 https://doaj.org/article/6613cfa0133b45b99845a0f1b17c6da1 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001253 |
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PLoS Neglected Tropical Diseases |
container_volume |
5 |
container_issue |
7 |
container_start_page |
e1253 |
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1766339566811217920 |