Artenimol is an artemisinin derivative and antimalarial agent used in the treatment of uncomplicated Plasmodium falciparum infections. It is used in combination with Piperaquine. Artemisinins, including Artenimol which is a major active metabolite of many artemisinins, are believed to bind to haem within the P. falciparum parasite. The source of this haem varies with the life stage of the parasite. When the parasite is in the early ring stage artemisinins are believed to bind haem produced by the parasite's haem biosynthesis pathway. In later stages artemisinins likely bind to haem released by haemoglobin digestion. Once bound to haem, artemisinins are thought to undergo activation involving ferrous iron via reductive scission which splits the endoperoxide bridge to produce a reactive oxygen. This reactive oxygen is thought to undergo a subsequent intramolecular hydrogen abstraction to produce a reactive carbon radical. The carbon radical is believed to be the source of the drugs potent activity against P. falciparum by alkylating a wide array of protein targets. The nature and magnitude of the effect on specific protein function as a result of this alkylation is unknown. One target which has been the focus of research is the sarco/endoplasmic reticulum Ca2+ ATPase pump of P. falciparum. Artemisinins have been found to irreversably bind to and inhibit this protein at a binding site similar to that of Thapsigargin.

Artenimol Pathway References