Open source drug research for schistosomiasis

Improving praziquantel

TDR news item
27 September 2011

Improvement of praziquantel, the drug of choice against schistosomiasis, is the expected outcome of a new collaboration based on open source drug development principles. Matthew Todd from the University of Sydney and TDR's Piero Olliaro have published two articles on this work – a commentary on the process in Nature Chemistry and a technical article in PLoS Neglected Tropical Diseases. The project is hosted online at the Synaptic Leap website and was funded through a unique collaboration between TDR and the Australian Research Council. The site contains data on chemical reactions aimed at producing a new version of praziquantel (PZQ), as a single enantiomer, thus eliminating the bitter taste and side effects of the treatment.

As an open source project, the research was open to anyone to take part. The authors write about the unexpected enthusiasm shown by industry, and the free input received from chemical companies who carried out experimental work. The project proceeded very quickly because of the inputs received from around the world, with a preliminary solution after less than a year of effort.

The work led to the identification of two approaches towards the production of praziquantel as a single enantiomer. One approach starts with commercially available praziquantel and involves a hydrolysis to an intermediate amine which is resolved with a derivative of tartaric acid. This method was discovered through an open collaboration on the internet. The second method, identified by a contract research organisation, employs a different intermediate that may be resolved with tartaric acid itself.

For more information, contact Dr Piero Olliaro.