Alkylation of human albumin by the antimalarial artemisinin.
The interaction between artemisinin and human serum was studied in vitro using [3H]dihydroartemisinin and [14C]artemisinin. Approximately 20% of added drug was covalently bound to albumin in 24 hr. The results 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 67,223 +/- 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 albumin probably involves thiol and amino groups via both iron-dependent and -independent reactions.
Yang
Y Z
YZ
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor 48109.
Asawamahasakda
W
W
Meshnick
S R
SR
D000478:Alkylation; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins; D002250:Carbon Radioisotopes; D006801:Humans; D007501:Iron; D007502:Iron Chelating Agents; D011485:Protein Binding / Q000187:drug effects; D012709:Serum Albumin / Q000737:chemistry*; D012717:Sesquiterpenes / Q000494:pharmacology*; D013997:Time Factors; D014316:Tritium
D000962:Antimalarials; D037621:Artemisinins; D002250:Carbon Radioisotopes; D007502:Iron Chelating Agents; D012709:Serum Albumin; D012717:Sesquiterpenes; D014316:Tritium; C031327:artemisinin; D007501:Iron