Artemisinins: their growing importance in medicine

Abstract

Artemisinins are derived from extracts of sweet wormwood (Artemisia annua) and are well established for the treatment of malaria, including highly drug-resistant strains. Their efficacy also extends to phylogenetically unrelated parasitic infections such as schistosomiasis. More recently, they have also shown potent and broad anticancer properties in cell lines and animal models. In this review, we discuss recent advances in defining the role of artemisinins in medicine, with particular focus on their controversial mechanisms of action. This safe and cheap drug class that saves lives at risk from malaria can also have important potential in oncology.

Figure 1

Chemical structures of artemisinins. Artemisinin (a) isolated in crystalline form in 1973 from Artemisia annua and derivatives dihydroartemisinin (DHA) (b), artemether (c), artesunate (d) and arteether (f) were first prepared by Chinese scientists in the 1970s . Artemisone (e), representative of a new class of artemisinin known as amino-artemisinins, is curative in clinical trials at one-third the dose regimen of artesunate. It is characterized by low toxicity . Artelinate (g) was prepared at the Walter Reed Army Institute of Research (http://wrair-www.army.mil), but was withdrawn because of toxicity concerns . Deoxyartemisinin (h), lacking the peroxide bridge, is biologically inert.

Figure I

Diagram showing the complex life cycle of Plasmodium falciparum. Abbreviations: AA, amino acids; Ap, apicoplast; ART, artemisinins; DV, digestive vacuole; ER, endoplasmic reticulum; G, Golgi apparatus; Hb, haemoglobin; Hz, haemozoin; M, mitochondrion; N, nucleus; RBC, red blood cell; TCTP, translationally controlled tumour protein.