Malaria, particularly as initiate by the parasite Plasmodium falciparum remains a major cause of (particularly infant) mortality in much of the developing world to this day.
Quinoline antimalarials have, until recently, been the mainstay of antimalarial chemotherapy. The current situation with many quinoline antimalarials (particularly chloroquine), however, is that resistant strains of the parasite have rendered these drugs ineffective. The mechanism through which quinolines accumulate in the food vacuole of the malaria parasite is proposed to be disrupted in resistant mutants. An alternative mechanism of directing quinolines to their sites of action is illustrated and the activity of these species on chloroquine resistant mutants is demonstrated.
An objective of modern discovery programmes is to generate agents that kill the parasite more rapidly. A method through which the rate at which a parasite experiences drug pressure can be assessed has been developed. The basis for this assessment is the rate at which the parasite increases ATP production - thought to be an indication of response to drug pressure. The use of data obtained using this methodology in the development of fast acting antimalarials such as a new series of fast acting artemisinin derivatives will be disclosed.