Evidence for a common non-heme chelatable-iron-dependent activation mechanism for semisynthetic and synthetic endoperoxide antimalarial drugs

(Chemical Equation Presented) The iron-y of fate: Isobole analyses of fluorescently labeled antimalarial endoperoxides with chelators selective for non-heme iron, and laser confocal microscopy studies within living malaria parasites have shown that the semisynthetic analogues of artemisinin and synthetic endoperoxides (see example) share a common mechanism of action involving chelatable-iron-mediated bioactivation (see images) and irreversible alkylation of parasite targets.