The 'neglected' parasite-borne diseases of leishmaniasis and Chagas disease affect some 18 million people worldwide, mostly in developing countries. If left untreated, both can be fatal, and indeed visceral leishmaniasis is thought to be the second largest parasitic cause of death after malaria. The few current available treatments exhibit toxicity side effects, are expensive, or show emerging resistance.

 

With the long term goal of contributing to the development of new therapies, we are targeting the synthesis and modification of several families of plant-derived natural products which demonstrate promising antiparasitic activity against Leishmania donovani and Trypanosoma cruzi (or related parasites). To do this, we are collaborating with parasitologist Prof André Tempone (Instituto Adolfo Lutz, São Paulo) and natural products isolation chemist Prof João Lago (ABC Federal University, São Paulo), to use simple natural products as starting points for this research.

 

We have developed a concise and cheap synthetic route to dehydrodieugenol-based targets which allows us to explore Structure Activity Relationships (SAR) in these compounds. Our synthesis is based on a key copper catalysed Ullmann coupling, allowing facile diversification  of the coupling partners and late stage modification on the benzylic ether position. We also work with Dr Richard Wheeler (University of Oxford) to investigate the Mechanism of Action for this family of compounds in Leishmania mexicana.