REVIEW All artemisinins used today are prodrugs of the biologically active metabolite dihydroartemisinin, which is active during the stage when the parasite is located inside red blood cells. Although there is no consensus regarding the mechanism through which artemisinin derivatives kill the parasites, several lines of evidence indicate that artemisinins exert their antimalarial action by perturbing redox homeostasis in malaria parasites. When the parasite that causes malaria infects a red blood cell, it consumes hemoglobin within its digestive vacuole, a process that generates oxidative stress. In one theory the iron of the heme directly reduces the peroxide bond in artemisinin, generating high-valent iron-oxo species and resulting in a cascade of reactions that produce reactive oxygen radicals which damages the parasite and lead to its death.
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