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

• Published in: PLoS neglected tropical diseases Vol. 10; no. 4; p. e0004659
• Main Authors: Mansour, Nuha R, Paveley, Ross, Gardner, J Mark F, Bell, Andrew S, Parkinson, Tanya, Bickle, Quentin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29-04-2016; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Anthelmintics - isolation & purification; Anthelmintics - pharmacology; Anthelmintics - toxicity; Biological Assay; Biology and Life Sciences; Care and treatment; Cell Line; Cell Survival - drug effects; Cytotoxicity; Dosage and administration; Drug Evaluation, Preclinical; Health screening; High-Throughput Screening Assays; Humans; Infections; Larva - drug effects; Library collections; Medicine and Health Sciences; Motility; Pharmaceutical industry; Pharmaceutical sciences; Physical Sciences; Praziquantel; R&D; Research & development; Research and Analysis Methods; Researchers; Risk factors; Schistosoma mansoni - drug effects; Schistosomiasis; Survival Analysis; Tropical diseases; Worms
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0004659

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.