Résumé
Glycerophospholipids, the main Plasmodium membrane constituents, mostly originate from the parasite enzymatic machinery, which relies on the scavenging and downstream metabolism of polar heads and fatty acids. At the blood stage, P. falciparum combines metabolic pathways found in bacteria, yeasts, and plants. Coordinated regulations between these pathways appear limited, and the vital importance of individual metabolic pathways remains to be clarified. The problem is even more complex as rodent and nonrodent malarial parasites differ in their phospholipid metabolic pathways. Extensive research on intraerythrocytic Plasmodium glycerophospholipid metabolism has revealed potential targets for chemotherapeutic interference; this involves the use of false precursors to deceive the parasite or inhibitors. The most advanced pharmacological approach is based on the use of choline analogs, the primary interference of which has been associated with locking the choline carrier. Such molecules inhibit P. falciparum asexual blood stages at single‐digit nanomolar concentrations, and cure Plasmodium vinckei malaria infection in mice at doses lower than 1mg kg
−1
. The potency and specificity of these molecules are most likely due to their unique ability to accumulate, nonreversibly, inside the intraerythrocytic parasite. The potent antimalarial activity of these derivatives may also be attributed to their compartmentalization within the parasite's food vacuole, where they bind to ferriprotoporphyrin IX. This exciting new class of compound is currently under development, while human Phase II clinical trials of T3/SAR97276 are ongoing for parenteral cures of severe malaria. This clinical candidate is structurally unrelated to existing antimalarial agents, and acts through new, independent mechanisms of action. The drug's unique properties are of tremendous interest in the role of an anti‐infectious agent, and indicate that the targeting of lipid metabolism is a valuable strategy in the development of new antiparasitic drugs.