Redox reaction of artemisinin with ferrous and ferric ions in aqueous buffer.
Artemisinin, a sesquiterpene with endoperoxide bond, possesses potent antimalarial activity against the ring and late stage of chloroqine-resistant Plasmodium falciparum malaria both in vitro and in vivo. The mode of antimalarial activity of artemisinin is iron-dependent. The aim of this study was to investigate the reactions of artemisinin with ferrous and ferric ions in aqueous buffer. Artemisinin generated a cycle of iron oxidation and reduction. It oxidized ferrous and reduced ferric ions with similar rate of reaction (k=10+/-0.5 M(-1) x s(-1) for ferrous and k=8.5+/-2.0 M(-1) x s(-1) for ferric ion). The major active product was dihydroartemisinin which exhibited antimalarial activity at least 3 times more potent than artemisinin. Dihydroartemisinin 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 dihydroartemisinin, which is responsible for antimalarial activity.
Sibmooh
N
N
Laboratory of Physical Chemistry, Molecular and Cellular Biology, Faculty of Science, Burapha University, Bangsaen, Chonburi, Thailand.
Udomsangpetch
R
R
Kujoa
A
A
Chantharaksri
U
U
Mankhetkorn
S
S
D000962:Antimalarials / Q000737:chemistry*; D037621:Artemisinins; D002021:Buffers; D003124:Colorimetry; D005290:Ferric Compounds / Q000737:chemistry*; D005296:Ferrous Compounds / Q000737:chemistry*; D007502:Iron Chelating Agents / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008670:Metals / Q000737:chemistry; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D012717:Sesquiterpenes / Q000737:chemistry*; D012996:Solutions
D000962:Antimalarials; D037621:Artemisinins; D002021:Buffers; D005290:Ferric Compounds; D005296:Ferrous Compounds; D007502:Iron Chelating Agents; D008670:Metals; D012717:Sesquiterpenes; D012996:Solutions; C031327:artemisinin; D010100:Oxygen