Heme Alkylation (Plasmodium)

Heme alkylation in *Plasmodium* refers to the covalent modification of free heme molecules within the malaria parasite, primarily by antimalarial drugs containing peroxide groups such as artemisinin derivatives and ozonides. This process is a key mechanism underlying the efficacy of these drugs against *Plasmodium falciparum*. Peroxide-based antimalarials are activated by intraparasitic iron—most likely from free heme—leading to generation of highly reactive carbon-centered radicals that alkylate the porphyrin ring of free heme at various meso positions, forming stable adducts and disrupting normal detoxification pathways.

Other names

Heme modificationPorphyrin alkylationFe(II)/Fe(III)-heme alkylation

Iron-mediated activation of peroxide antimalarials leads to radical formation and subsequent covalent modification (alkylation) of free heme, disrupting its detoxification and leading to parasite death.