artemisiini

Artemisiniini (artemisinin) is a group of sesquiterpene lactones with an endoperoxide moiety, produced by the plant Artemisia annua. The term commonly refers to artemisinin and its semi-synthetic derivatives used as antimalarial agents: artesunate, artemether, and dihydroartemisinin, among others.

Source and chemistry: Artemisinin is a sesquiterpene lactone with a peroxide bridge essential to activity. It is extracted from Artemisia annua but also produced through semi-synthesis from artemisinic acid, and is now manufactured by microbial fermentation and plant extraction.

Mechanism and clinical use: Activation by ferrous iron within Plasmodium parasites cleaves the peroxide, generating reactive radicals that alkylate parasite proteins and lipids, rapidly reducing parasite load. Activity is strongest against early blood-stage parasites; partner drugs in ACTs extend activity and manage resistance. Artemisinins are the cornerstone of ACTs for uncomplicated Plasmodium falciparum malaria, often given as artesunate–mefloquine, artemether–lumefantrine, or dihydroartemisinin–piperaquine. They act rapidly but have short half-lives, necessitating combination with longer-acting drugs.

Production and history: The antimalarial properties were discovered in the 1970s by Youyou Tu, earning the Nobel Prize in Physiology or Medicine in 2015. Commercial production relied on extraction from Artemisia annua; recent advances include yeast-based production of artemisinic acid and subsequent chemical conversion to artemisinin.

Resistance and safety: Resistance through delayed parasite clearance has emerged in some regions; surveillance is ongoing. Artemisinins are generally well tolerated; common adverse effects include gastrointestinal symptoms and transient liver enzyme elevations; rare neurotoxicity at high doses.