Halofantrine is an synthetic antimalarial used for the treatment of severe malaria. It is effective against multi drug resistant (including mefloquine resistant) P. falciparum malaria. The mechanism of action of Halofantrine may be similar to that of chloroquine, quinine, and mefloquine; by forming toxic complexes with ferritoporphyrin IX that damage the membrane of the parasite. The plasmodium falciparum invades the erythrocytes in blood. Halofantrine accumulates in the parasite’s food vacuole and inhibits the enzyme heme ligase. Heme ligase is involved in hemoglobin breakdown. Hemoglobin from the erythrocyte is broken down in the digestive vacuole of the parasite. Hemoglobin is first broken down into heme and globin. Globin is further broken down to amino acids which are used by the parasite for nutrition and protein synthesis. Therefore, hemoglobin breakdown is essential for the parasite survival. The heme from hemoglobin is toxic to the parasite and is further broken down by heme ligase to detoxify heme. By halofantrine inhibiting heme ligase, there is a build up of heme in the parasite vacuole which becomes toxic to the parasite, thereby killing it.

Halofantrine Pathway References