ALKYLATION OF HUMAN ALBUMIN BY THE ANTIMALARIAL ARTEMISININ

The interaction between artemisinin and human serum was studied in vit ro using H-3!dihydroartemisinin and C-14!artemisinin. Approximately 20% of added drug was covalently bound to albumin in 24 hr. The result s of electrospray ionization mass spectra showed that albumin had an M (r) value of 66,745 +/- 35 and the drug-bound albumin had an M(r) of 6 7,223 +/- 34. The binding was blocked 15 and 58% by iodoacetamide (IA) and N-ethylmaleimide, respectively, and 80% by the combination of IA and succinic anhydride. Hemin and Fe2+ increased the binding by 40 and 10%, respectively, whereas deferoxamine inhibited the binding by 10%. Therefore, we conclude that the binding between artemisinin and album in probably involves thiol and amino groups via both iron-dependent an d independent reactions.