Artemisinin antimalarials: mechanisms of action and resistance.
Artemisinin derivatives are an important new class of antimalarial agents. These compounds contain endoperoxide bridges which are essential for antimalarial activity. Artemisinin is believed to act via a two-step mechanism. Artemisinin is first activated by intraparasitic heme-iron which catalyzes the cleavage of this endoperoxide. A resulting free radical intermediate may then kill the parasite by alkylating and poisoning one or more essential malarial protein(s). No clinically relevant artemisinin-resistant human malaria has yet been reported. However, an artemisinin-resistant strain of murine malaria has been developed and may offer clues to the kinds of resistance that may someday develop in human malarias.
Meshnick
S R
SR
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor 48109, USA. Meshnick@umich.edu
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000145:classification / Q000494:pharmacology* / Q000627:therapeutic use; D037621:Artemisinins; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects; D015800:Protozoan Proteins / Q000187:drug effects; D012717:Sesquiterpenes / Q000737:chemistry / Q000145:classification / Q000494:pharmacology* / Q000627:therapeutic use
D000962:Antimalarials; D037621:Artemisinins; D015800:Protozoan Proteins; D012717:Sesquiterpenes; C031327:artemisinin