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2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm
The human whipworm Trichuris trichiura is a parasite that infects around 500 million people globally, with consequences including damage to physical growth and educational performance. Current drugs such as mebendazole have a notable lack of efficacy against whipworm, compared to other soil-transmit...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062138/ https://www.ncbi.nlm.nih.gov/pubmed/29995893 http://dx.doi.org/10.1371/journal.pntd.0006487 |
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author | Partridge, Frederick A. Forman, Ruth Willis, Nicky J. Bataille, Carole J. R. Murphy, Emma A. Brown, Anwen E. Heyer-Chauhan, Narinder Marinič, Bruno Sowood, Daniel J. C. Wynne, Graham M. Else, Kathryn J. Russell, Angela J. Sattelle, David B. |
author_facet | Partridge, Frederick A. Forman, Ruth Willis, Nicky J. Bataille, Carole J. R. Murphy, Emma A. Brown, Anwen E. Heyer-Chauhan, Narinder Marinič, Bruno Sowood, Daniel J. C. Wynne, Graham M. Else, Kathryn J. Russell, Angela J. Sattelle, David B. |
author_sort | Partridge, Frederick A. |
collection | PubMed |
description | The human whipworm Trichuris trichiura is a parasite that infects around 500 million people globally, with consequences including damage to physical growth and educational performance. Current drugs such as mebendazole have a notable lack of efficacy against whipworm, compared to other soil-transmitted helminths. Mass drug administration programs are therefore unlikely to achieve eradication and new treatments for trichuriasis are desperately needed. All current drug control strategies focus on post-infection eradication, targeting the parasite in vivo. Here we propose developing novel anthelmintics which target the egg stage of the parasite in the soil as an adjunct environmental strategy. As evidence in support of such an approach we describe the actions of a new class of anthelmintic compounds, the 2,4-diaminothieno[3,2-d]pyrimidines (DATPs). This compound class has found broad utility in medicinal chemistry, but has not previously been described as having anthelmintic activity. Importantly, these compounds show efficacy against not only the adult parasite, but also both the embryonated and unembryonated egg stages and thereby may enable a break in the parasite lifecycle. |
format | Online Article Text |
id | pubmed-6062138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-60621382018-08-03 2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm Partridge, Frederick A. Forman, Ruth Willis, Nicky J. Bataille, Carole J. R. Murphy, Emma A. Brown, Anwen E. Heyer-Chauhan, Narinder Marinič, Bruno Sowood, Daniel J. C. Wynne, Graham M. Else, Kathryn J. Russell, Angela J. Sattelle, David B. PLoS Negl Trop Dis Research Article The human whipworm Trichuris trichiura is a parasite that infects around 500 million people globally, with consequences including damage to physical growth and educational performance. Current drugs such as mebendazole have a notable lack of efficacy against whipworm, compared to other soil-transmitted helminths. Mass drug administration programs are therefore unlikely to achieve eradication and new treatments for trichuriasis are desperately needed. All current drug control strategies focus on post-infection eradication, targeting the parasite in vivo. Here we propose developing novel anthelmintics which target the egg stage of the parasite in the soil as an adjunct environmental strategy. As evidence in support of such an approach we describe the actions of a new class of anthelmintic compounds, the 2,4-diaminothieno[3,2-d]pyrimidines (DATPs). This compound class has found broad utility in medicinal chemistry, but has not previously been described as having anthelmintic activity. Importantly, these compounds show efficacy against not only the adult parasite, but also both the embryonated and unembryonated egg stages and thereby may enable a break in the parasite lifecycle. Public Library of Science 2018-07-11 /pmc/articles/PMC6062138/ /pubmed/29995893 http://dx.doi.org/10.1371/journal.pntd.0006487 Text en © 2018 Partridge et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Partridge, Frederick A. Forman, Ruth Willis, Nicky J. Bataille, Carole J. R. Murphy, Emma A. Brown, Anwen E. Heyer-Chauhan, Narinder Marinič, Bruno Sowood, Daniel J. C. Wynne, Graham M. Else, Kathryn J. Russell, Angela J. Sattelle, David B. 2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm |
title | 2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm |
title_full | 2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm |
title_fullStr | 2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm |
title_full_unstemmed | 2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm |
title_short | 2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm |
title_sort | 2,4-diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062138/ https://www.ncbi.nlm.nih.gov/pubmed/29995893 http://dx.doi.org/10.1371/journal.pntd.0006487 |
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