Activity Profile of an FDA-Approved Compound Library against Schistosoma mansoni.
BACKGROUND:As plans to expand mass drug treatment campaigns to fight schistosomiasis form, worries about reliance on praziquantel as the sole available treatment motivate the investigation for novel antischistosomal compounds. Drug repurposing might be an inexpensive and effective source of novel an...
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ftdoajarticles:oai:doaj.org/article:3a066e2b87f54b9ebd0cd2afbaabecab 2023-05-15T15:08:30+02:00 Activity Profile of an FDA-Approved Compound Library against Schistosoma mansoni. Gordana Panic Mireille Vargas Ivan Scandale Jennifer Keiser 2015-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003962 https://doaj.org/article/3a066e2b87f54b9ebd0cd2afbaabecab EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4521867?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003962 https://doaj.org/article/3a066e2b87f54b9ebd0cd2afbaabecab PLoS Neglected Tropical Diseases, Vol 9, Iss 7, p e0003962 (2015) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2015 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003962 2022-12-31T05:29:48Z BACKGROUND:As plans to expand mass drug treatment campaigns to fight schistosomiasis form, worries about reliance on praziquantel as the sole available treatment motivate the investigation for novel antischistosomal compounds. Drug repurposing might be an inexpensive and effective source of novel antischistosomal leads. METHODOLOGY:1600 FDA approved compounds were first assayed against Schistosoma mansoni schistosomula at a concentration of 10 µM. Active compounds identified from this screen were advanced to the adult worm screen at 33.33 µM, followed by hit characterization. Leads with complementary pharmacokinetic and toxicity profiles were then selected for in vivo studies. PRINCIPAL FINDINGS:The in vitro screen identified 121 and 36 compounds active against the schistosomula and adult stage, respectively. Further, in vitro characterization and comparison with already available pharmacokinetic and toxicity data identified 11 in vivo candidates. Doramectin (10 mg/kg) and clofazimine (400 mg/kg) were found to be active in vivo with worm burden reductions of 60.1% and 82.7%, respectively. CONCLUSIONS/SIGNIFICANCE:The work presented here expands the knowledge of antischistosomal properties of already approved compounds and underscores variations observed between target-based and phenotypic approaches and among laboratories. The two in vivo-active drugs identified in this study, doramectin and clofazimine are widely available and present as novel drug classes as starting points for further investigation. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 9 7 e0003962 |
institution |
Open Polar |
collection |
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 Gordana Panic Mireille Vargas Ivan Scandale Jennifer Keiser Activity Profile of an FDA-Approved Compound Library against Schistosoma mansoni. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:As plans to expand mass drug treatment campaigns to fight schistosomiasis form, worries about reliance on praziquantel as the sole available treatment motivate the investigation for novel antischistosomal compounds. Drug repurposing might be an inexpensive and effective source of novel antischistosomal leads. METHODOLOGY:1600 FDA approved compounds were first assayed against Schistosoma mansoni schistosomula at a concentration of 10 µM. Active compounds identified from this screen were advanced to the adult worm screen at 33.33 µM, followed by hit characterization. Leads with complementary pharmacokinetic and toxicity profiles were then selected for in vivo studies. PRINCIPAL FINDINGS:The in vitro screen identified 121 and 36 compounds active against the schistosomula and adult stage, respectively. Further, in vitro characterization and comparison with already available pharmacokinetic and toxicity data identified 11 in vivo candidates. Doramectin (10 mg/kg) and clofazimine (400 mg/kg) were found to be active in vivo with worm burden reductions of 60.1% and 82.7%, respectively. CONCLUSIONS/SIGNIFICANCE:The work presented here expands the knowledge of antischistosomal properties of already approved compounds and underscores variations observed between target-based and phenotypic approaches and among laboratories. The two in vivo-active drugs identified in this study, doramectin and clofazimine are widely available and present as novel drug classes as starting points for further investigation. |
format |
Article in Journal/Newspaper |
author |
Gordana Panic Mireille Vargas Ivan Scandale Jennifer Keiser |
author_facet |
Gordana Panic Mireille Vargas Ivan Scandale Jennifer Keiser |
author_sort |
Gordana Panic |
title |
Activity Profile of an FDA-Approved Compound Library against Schistosoma mansoni. |
title_short |
Activity Profile of an FDA-Approved Compound Library against Schistosoma mansoni. |
title_full |
Activity Profile of an FDA-Approved Compound Library against Schistosoma mansoni. |
title_fullStr |
Activity Profile of an FDA-Approved Compound Library against Schistosoma mansoni. |
title_full_unstemmed |
Activity Profile of an FDA-Approved Compound Library against Schistosoma mansoni. |
title_sort |
activity profile of an fda-approved compound library against schistosoma mansoni. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2015 |
url |
https://doi.org/10.1371/journal.pntd.0003962 https://doaj.org/article/3a066e2b87f54b9ebd0cd2afbaabecab |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 9, Iss 7, p e0003962 (2015) |
op_relation |
http://europepmc.org/articles/PMC4521867?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003962 https://doaj.org/article/3a066e2b87f54b9ebd0cd2afbaabecab |
op_doi |
https://doi.org/10.1371/journal.pntd.0003962 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
9 |
container_issue |
7 |
container_start_page |
e0003962 |
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1766339858763087872 |