Research projects in the group are in the field of bioinorganic chemistry. Current work is centred on the mechanism of malaria pigment (haemozoin) formation and the mechanism of action of quinoline and related antimalarial drugs and related haem speciation studies. This information is being used to develop principles for the design of new antimalarials.
The malaria parasite spends a part of its life-cycle in the host’s red blood cells. During this stage it utilises haemoglobin as a food source, breaking down the protein to amino acids and releasing the haem moiety intact. Haem is potentially toxic and the parasite deals with this by converting it to haemozoin. Current evidence indicates that drugs such as chloroquine act by inhibiting the formation of haemozoin and thus block haem detoxification. Our work is focussed on structure-activity relationships in haemozoin-inhibiting antimalarial compounds. Studies include the following:
- Molecular mechanisms of haemozoin and β-haematin formation, including lipid mediated β-haematin formation and use of proteomic and lipidomic methods to investigate molecules associated with haemozoin in the malaria parasite.
- Investigation of structure-activity relationships in new antimalarial scaffolds identified from high throughput screening, including β-haematin inhibition, activity against malaria parasites grown in culture and distribution of haem species in treated parasites.
- Investigation of the antimalarial activities of dual-functioning quinolines which can act both as antimalarials and chloroquine chemosensitizers.
- Design and use of fluorescent drug analogues to probe localisation and mechanism of drug action.
- Structures of ferrihaem species and ferrihaem-drug complexes.