2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm.

• Published in: PLOS Neglected Tropical Diseases
• Main Authors: Frederick A Partridge, Ruth Forman, Nicky J Willis, Carole J R Bataille, Emma A Murphy, Anwen E Brown, Narinder Heyer-Chauhan, Bruno Marinič, Daniel J C Sowood, Graham M Wynne, Kathryn J Else, Angela J Russell, David B Sattelle
• Format: Article in Journal/Newspaper
• Language: English
• Published: Public Library of Science (PLoS) 2018
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Public aspects of medicine; RA1-1270; Arctic
• Online Access: https://doi.org/10.1371/journal.pntd.0006487; https://doaj.org/article/dbfa1530a47d45d9ab4a45f4e2a752df

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.