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...

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Main Authors: Frederick A Partridge (Author), Ruth Forman (Author), Nicky J Willis (Author), Carole J R Bataille (Author), Emma A Murphy (Author), Anwen E Brown (Author), Narinder Heyer-Chauhan (Author), Bruno Marinič (Author), Daniel J C Sowood (Author), Graham M Wynne (Author), Kathryn J Else (Author), Angela J Russell (Author), David B Sattelle (Author)
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Published: Public Library of Science (PLoS), 2018-07-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Frederick A Partridge  |e author 
700 1 0 |a Ruth Forman  |e author 
700 1 0 |a Nicky J Willis  |e author 
700 1 0 |a Carole J R Bataille  |e author 
700 1 0 |a Emma A Murphy  |e author 
700 1 0 |a Anwen E Brown  |e author 
700 1 0 |a Narinder Heyer-Chauhan  |e author 
700 1 0 |a Bruno Marinič  |e author 
700 1 0 |a Daniel J C Sowood  |e author 
700 1 0 |a Graham M Wynne  |e author 
700 1 0 |a Kathryn J Else  |e author 
700 1 0 |a Angela J Russell  |e author 
700 1 0 |a David B Sattelle  |e author 
245 0 0 |a 2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm. 
260 |b Public Library of Science (PLoS),   |c 2018-07-01T00:00:00Z. 
500 |a 1935-2727 
500 |a 1935-2735 
500 |a 10.1371/journal.pntd.0006487 
520 |a 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. 
546 |a EN 
690 |a Arctic medicine. Tropical medicine 
690 |a RC955-962 
690 |a Public aspects of medicine 
690 |a RA1-1270 
655 7 |a article  |2 local 
786 0 |n PLoS Neglected Tropical Diseases, Vol 12, Iss 7, p e0006487 (2018) 
787 0 |n https://doi.org/10.1371/journal.pntd.0006487 
787 0 |n https://doaj.org/toc/1935-2727 
787 0 |n https://doaj.org/toc/1935-2735 
856 4 1 |u https://doaj.org/article/dbfa1530a47d45d9ab4a45f4e2a752df  |z Connect to this object online.