Artemisinin

Lore & Background

Artemisinin can be extracted from the herb Artemisia annua (sweet wormwood), which is used in traditional Chinese medicine. Alternatively, it can be prepared by a semi-synthetic method from a precursor compound that can be produced using a genetically engineered yeast, which is much more efficient than extraction from the plant. Artemisinin and its derivatives are all sesquiterpene lactones containing an unusual peroxide bridge, the endoperoxide 1,2,4-trioxane ring responsible for their antimalarial properties. Few other natural compounds with such a peroxide bridge are known. Artemisinin and its derivatives have been used for the treatment of malarial and parasitic worm (helminth) infections. Advantages of such treatments over other anti-parasitics include faster parasite elimination and broader efficacy across the parasite life-cycle; disadvantages include their low bioavailability, poor pharmacokinetic properties, and high cost. Use of the drug by itself as a monotherapy is explicitly discouraged by the World Health Organization, as there have been signs that malarial parasites are developing resistance to the drug. The World Health Organization recommends artemisinin or one of its derivatives — typically in combination with a longer-lasting partner drug — as frontline therapy for all cases of malaria. For uncomplicated malaria, the WHO recommends three days of oral treatment with any of five artemisinin-based combination therapies. For severe malaria, the WHO recommends intravenous or intramuscular treatment with the artemisinin derivative artesunate for at least 24 hours.

Reader's Guide

Artemisinin represents a critical advance in malaria treatment, particularly for Plasmodium falciparum, the most deadly malaria parasite. The drug's unique endoperoxide bridge enables rapid parasite killing across all life-cycle stages, offering advantages over older antimalarials. However, artemisinin's poor bioavailability and short half-life necessitate combination with longer-acting partner drugs to prevent recurrence and delay resistance. The WHO discourages monotherapy and promotes rational use to preserve efficacy. Despite these challenges, artemisinin and its derivatives remain indispensable in both uncomplicated and severe malaria, with ongoing research into derivatives and simplified analogs to improve pharmacokinetics and overcome resistance.

Did You Know?

• Artemisinin contains an unusual endoperoxide 1,2,4-trioxane ring, which is responsible for its antimalarial properties.
• The World Health Organization recommends artemisinin-based combination therapies (ACTs) as frontline therapy for all cases of malaria.