title: High Throughput Screening Identifies Novel Lead Compounds with Activity against Larval, Juvenile and Adult Schistosoma mansoni.
abstract: 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.
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Nuha R
authors.initials: NR
authors.lastname: Mansour
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Ross
authors.initials: R
authors.lastname: Paveley
authors.affiliation: Salvensis, Discovery Park House, Discovery Park, Sandwich, Kent, United Kingdom.
authors.forename: J Mark F
authors.initials: JM
authors.lastname: Gardner
authors.affiliation: Salvensis, Discovery Park House, Discovery Park, Sandwich, Kent, United Kingdom.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Bell
authors.affiliation: Salvensis, Discovery Park House, Discovery Park, Sandwich, Kent, United Kingdom.
authors.forename: Tanya
authors.initials: T
authors.lastname: Parkinson
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Bickle
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000302:isolation & purification* / Q000494:pharmacology* / Q000633:toxicity; D001681:Biological Assay; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D057166:High-Throughput Screening Assays; D006801:Humans; D007814:Larva / Q000187:drug effects; D012550:Schistosoma mansoni / Q000187:drug effects*; D016019:Survival Analysis
chemical_list: D000871:Anthelmintics