Screening of a plant derived natural produt library for anthelmintic properties (Presentation)

Student: Jennifer Edwards
Company: Phytoquest Ltd
Academic Supervisor: Prof Karl Hoffman & Prof Peter Brophy

Schistosomiasis is a debilitating, reoccurring parasitic disease, caused by blood flukes contained within the genus Schistosoma. The magnitude of the disease is demonstrated by the parasite’s broad worldwide distribution, which is currently reported in 78 countries with an estimate of 200 million people being infected and a further 779 million people being at risk of infection. Over reliance on a singular chemotherapy, praziquantel (PZQ), for mass drug administration (MDA) programmes, as well as reports of possible emerging resistance to the only drug in use, put future schistosomiasis control methods into question.

In response to this, the development of new anthelmintics (drugs active against the parasite) is a necessary step for the long-term control of the disease. Based on the anti-parasitic successes of artemisinin (a plant-derived compound active against the malaria parasite), plant-derived natural products offer a potential rich resource for the discovery of new anthelmintics.

To this end, in vitro anti-schistosomal screening of 47 structurally-related plant-derived compounds was performed on the blood fluke Schistosoma mansoni within the Hoffmann Parasitology research group at Aberystwyth University.

The MPhil project was supported financially by the KESS scholarship which allowed the collaboration of a Welsh SME PhytoQuest and the previously mentioned academic laboratory. This collaboration has allowed for a screen of extremely pure plant-derived compounds, provided by the Welsh industrial collaborator, to be performed assessing the selective activity of the library against a species of parasitic worms of veterinary and biomedical importance.

Further to this, the activity of this compound library towards a parasitic disease of tremendous veterinary importance in Wales, liver fluke (Fasciola hepatica), was also assessed in this MPhil in vitro screen. From these experiments, one compound of significant interest has proven to show activity against both parasites whilst showing no/ low toxicity to a mammalian cell line.

The compound has been shown to kill the juvenile life stages of both parasites at biologically relevant concentrations. After further analysis, the compounds activity against the adult life stage of S. mansoni also demonstrated phenotypic and biological affects which included deficiencies in worm pairing and motility, reductions in egg output and breaches in tegumental integrity. Confocal laser scanning microscopy also showed that the compound affected the normal formation of eggs within adult females. These alterations in parasite and egg phenotype would have a significant impact on the parasite’s survival within the human/ animal host and are a strong platform to support further investigations into this chemical class of compounds against helminth parasitic worms.

Findings from this work provide valuable information about the properties of these structurally related plant-derived compounds and demonstrate their potential as novel anthelmintic leads. Collaborations and outcomes that have resulted from this project include an NRN PhD application which will be a collaboration between Aberystwyth and Cardiff, a pending high quality publication, a patent application and extensive advertisement of the SME PhytoQuest at many national and international meetings and conferences that I have attended as part of the project regarding natural product drug discovery.