Optimisation of phosphodiesterase inhibitors to provide in vivo proof of concept for development of a new antimalarial drug

Drug-resistant malaria parasites are widespread and new antimalarial drugs are needed urgently. 

We have identified a series of small molecule inhibitors which target the malaria parasite phosphodiesterases (PDEs). Some of these compounds block the development of blood stage parasites, which cause disease symptoms, and sexual stage parasites, which mediate transmission to mosquitoes. One of the major advantages of this strategy is that safe drugs that target PDEs are already being used to treat other diseases. Chemists at the not-for-profit company Salvensis will design numerous novel versions of these compounds to be tested for activity on malaria parasites. 

The aim of this project is to generate a PDE inhibitor that will be suitable to progress to the next stage of the drug discovery pipeline. The long-term aim is to develop a dual-action antimalarial drug that can treat individuals and break the cycle of transmission in the wider population.