RESEARCH INTERESTS 

My research lies 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. 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. Current work is focussed on structure-activity relations in quinoline and related antimalarial drugs and their congeners. The mechanism of synthetic haemozoin (beta-haematin) formation is also under investigation using model systems that mimic the biological environment.

 Synthetic haemozoin prepared at an aqueous/ octanol interface at 37 °C and pH 4.8.

REPRESENTATIVE PUBLICATIONS

Egan, T. J.; Ross, D. C.; Adams, P. A. Quinoline anti-malarial drugs inhibit spontaneous formation of beta-haematin (malaria pigment). FEBS Lett. 1994, 352, 54-57

Egan, T. J.; Mavuso, W. W.; Ross, D. C.; Marques, H. M. Thermodynamic factors controlling the interaction 
of quinoline antimalarial drugs with ferriprotoporphyrin IX. J. Inorg. Biochem. 1997, 68, 137-145

Egan, T. J.; Hunter, R.; Kaschula, C. H.; Marques, H. M.; Misplon, A.; Walden, J. C. Structure-function relationships in aminoquinolines: effect of amino and chloro groups on quinoline-hematin complex formation, inhibition of beta-hematin formation, and antiplasmodial activity. J. Med. Chem. 2000, 43, 283-291

Egan, T. J.; Mavuso, W. W.; Ncokazi, K. K. The mechanism of beta-hematin formation in acetate solution. Parallels between hemozoin formation and biomineralization processes. Biochemistry 2001, 40, 204-213

Egan, T. J.; Combrinck, J. M.; Egan, J.; Hearne, G. R.; Marques, H. M.; Ntenteni, S.; Sewell, B. T.; Smith, P. J.; Taylor, D.; van Schalkwyk, D. A.; Walden, J. C. Fate of haem iron in the malaria parasite Plasmodium falciparum. Biochem. J. 2002, 365, 343-347

Kaschula, C. H.; Egan, T. J.; Hunter, R.; Basilico, N.; Parapini, S.; Taramelli, D.; Pasini, E.; Monti, D. Structure-activity relationships in 4-aminoquinoline antiplasmodials. The role of the group at the 7-position. J. Med. Chem. 2002, 45, 3531-3539

Ncokazi, K. K.; Egan, T. J. A colorimetric high-throughput beta-hematin inhibition screening assay for use in the search for antimalarial compounds. Anal. Biochem. 2005, 338, 306-319

 Egan, T. J.; Koch, K. R.; Swan, P. L.; Clarkson, C.; Van Schalkwyk, D. A.; Smith, P. J. In vitro antimalarial activity of a series of cationic 2,2'-bipyridyl- and 1,10-phenanthrolineplatinum(II) benzoylthiourea complexes.
J. Med. Chem. 2004, 47, 2926-2934

Egan, T. J.; Chen, J. Y.-J.; de Villiers, K. A.; Mabotha, T. E.; Naidoo, K. J.; Ncokazi, K. K.; Langford, S. J.; McNaughton, D.; Pandiancherri, S.; Wood, B. R. Haemozoin (beta-haematin) biomineralization occurs by self-assembly near the lipid/water interface. FEBS Lett. 2006, 580, 5105-5110