High Throughput Screening Identifies Novel Lead Compounds with Activity against Larval, Juvenile and Adult Schistosoma mansoni.

An estimated 600 million people are affected by the helminth disease schistosomiasis caused by parasites of the genus Schistosoma. There is currently only one drug recommended for treating schistosomiasis, praziquantel (PZQ), which is effective against adult worms but not against the juvenile stage....

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Bibliographic Details
Published in:PLOS Neglected Tropical Diseases
Main Authors: Nuha R Mansour, Ross Paveley, J Mark F Gardner, Andrew S Bell, Tanya Parkinson, Quentin Bickle
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2016
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Online Access:https://doi.org/10.1371/journal.pntd.0004659
https://doaj.org/article/d3931aef593f48d39c5e473c5df191f8
Description
Summary:An estimated 600 million people are affected by the helminth disease schistosomiasis caused by parasites of the genus Schistosoma. There is currently only one drug recommended for treating schistosomiasis, praziquantel (PZQ), which is effective against adult worms but not against the juvenile stage. In an attempt to identify improved drugs for treating the disease, we have carried out high throughput screening of a number of small molecule libraries with the aim of identifying lead compounds with balanced activity against all life stages of Schistosoma. A total of almost 300,000 compounds were screened using a high throughput assay based on motility of worm larvae and image analysis of assay plates. Hits were screened against juvenile and adult worms to identify broadly active compounds and against a mammalian cell line to assess cytotoxicity. A number of compounds were identified as promising leads for further chemical optimization.