Ferroquine: The Antimalarial Drug of the Future

Malaria is a parasitic disease which afflicts approximately 500 million people and causes more than 1 million deaths each year. Of the plasmodium species infecting humans, P. falciparum is the principal causative agent of malaria, responsible for 90% of deaths. Among the known antimalarials, chloroquine (CQ), a 4-aminoquinoline, is as a potent and non-expensive drug, used worldwide by poor populations. In the last years, P. falciparum has developed resistance to CQ, with the appearance of multiresistant strains. Therefore efforts have been directed to the discovery of new antimalarials. Ferroquine (FQ, SR97193), an analogue of CQ, presents itself as a great candidate. It contains a ferrocenyl group as an integral part of the side chain of CQ. FQ is able to overcome the CQ resistance, and its mechanism of action has been the subject of intensive investigation. It is able to inhibit formation of hemozoin and to generate reactive oxygen species. This mini- review covers mainly the modifications made to the structure of Ferroquine so far, in order to try to elucidate its mechanism of action.