Artemisinin, a sesquiterpene with endoperoxide bond, possesses potent antim
alarial activity against the ring and late stage of chloroqine-resistant Pl
asmodium falciparum malaria both in vitro and in vivo. The mode of antimala
rial activity of artemisinin is iron-dependent. The aim of this study was t
o investigate the reactions of artemisinin with ferrous and ferric ions in
aqueous buffer. Artemisinin generated a cycle of iron oxidation and reducti
on. It oxidized ferrous and reduced ferric ions with similar rate of reacti
on (k=10 +/-0.5 M-1.s(-1) for ferrous and k=8.5 +/-2.0 M-1.s(-1) for ferric
ion). The major active product was dihydroartemisinin which exhibited anti
malarial activity at least 3 times more potent than artemisinin. Dihydroart
emisinin preferably binds to ferric ion, forming ferric-dihydroartemisinin
complex. The re-oxidation of the complex gives artemisinin and ferric ion.
This suggests that in aqueous buffer, the reaction of artemisinin with iron
may give rise to the active reaction products, one of them being dihydroar
temisinin, which is responsible for antimalarial activity.