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.
Highlights
Schistosomiasis is a potentially severe helminthic disease causing widespread morbidity and affecting an estimated 600 million people [1]
We have identified quality chemical leads with balanced activity against all life stages of the parasite and with a good window over cytotoxicity, which could form the basis of an exciting new drug discovery project
There is a need for new schistosomicides with activity against all life stages and this has led to renewed interest in research into drug discovery using both phenotypic and target-based approaches
Summary
Schistosomiasis is a potentially severe helminthic disease causing widespread morbidity and affecting an estimated 600 million people [1]. There is a need for new schistosomicides with activity against all life stages and this has led to renewed interest in research into drug discovery using both phenotypic and target-based approaches. These include development and application of whole organism screens for compound testing [8], target-based drug discovery [9] and identification of putative molecular targets by analysis of the annotated schistosome sequences [10]. We here report the screening of almost 300,000 small molecule compounds provided from pharmaceutical companies, charitable organizations and commercial sources and describe a number of promising new leads for further chemical optimization
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
