AN INVESTIGATION INTO THE ANTIMALARIAL ACTIVITY OF METAL CHELATORS

Malaria remains one of the greatest problems facing developing nations, especially in sub-Saharan Africa. Part of the problem stems from increased resistance to current treatments hence there is a large drive to develop novel antimalarial compounds. Several chelating compounds, including 8-hydroxyquinoline (8-HQ), 1,10-phenanthroline (1,10-phen) and 2,2:6,2-terpyridine (terpy), have disputed activities (8-HQ and 1,10-phen) or are untested (terpy). Furthermore the mechanism(s) by which these ligands and/or their complexes with metal ions exhibit their toxic effect is unknown. In order to resolve these issues, a study of the antimalarial activities of the free ligands, the ligands complexed with metal ions (Au3+, Cu2+, Fe3+, Pd2+ and Pt2+), and the ligands with free metals in solution were measured. The ligands, complexes and metals were also tested for their ability to inhibit β-haematin formation, the mode of action ascribed to the most widely used antimalarial, chloroquine. The background toxicity levels of the various metal ions (previously unreported) were also measured and are reported here. None of the ligands were found to have particularly high activity (al