Natural product inspired leads against Leishmaniasis and Chagas disease

Chagas disease (caused by the parasite Trypanosoma cruzi) and cutaneous and visceral leishmaniasis (caused by Leishmania spp.) are neglected tropical diseases that affect tens of millions of people worldwide. These diseases are often fatal, and treatments are limited in efficacy, exhibiting severe side-effects.

A family of natural products extracted from the Brazilian plant Nectandra leucantha has been shown to have good activity against these parasites.

In this project I will combine synthetic organic chemistry with cell biology to explore these synthetically accessible natural products as a potential source of new therapeutic leads, focussing on improving their pharmacological profile.

I will also identify molecular targets and mechanism of action of promising compounds, using various techniques including tracking fluorescently labelled analogues and photolabile crosslinking.

I will carry out genome mutation of Leishmania and selection for compound resistance, followed by genome sequencing to identify genes likely to be involved in the mechanism of action of these compounds.

These studies will help to discover novel therapeutics with improved anti-parasitic activity, and their potential cellular targets.