Haemozoin Formation as a Target for the Rational Design of New Antimalarials

Owing to the widespread occurrence of drug resistance, there is now an urgent need for new antimalarial drugs. There is compelling evidence that the target of the historically most important group of antimalarials, the quinolines, remains useful for the design of new drugs. Currently available data suggest that these drugs inhibit the disposal of haemoglobin derived haematin during the blood-stage of the malaria parasite. This article reviews recent findings concerning the disposal of haematin in the food vacuole of the malaria parasite P. falciparum, the interaction of quinoline antimalarials with haematin and their inhibition of haemozoin formation. Emphasis is also placed on recently reported structure-activity relationships and possible ways forward in the discovery and design of new drugs of this type.