Alkylation of human albumin by the antimalarial artemisinin

• Published in: Biochemical pharmacology Vol. 46; no. 2; pp. 336 - 339
• Main Authors: Ying-Zi, Yang, Asawamahasakda, Wanida, Meshnick, Steven R.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 20.07.1993; Elsevier Science
• Subjects: Alkylation; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - pharmacology; Antiparasitic agents; Artemisinins; Biological and medical sciences; Carbon Radioisotopes; Humans; Iron; Iron Chelating Agents; Medical sciences; Pharmacology. Drug treatments; Protein Binding - drug effects; Serum Albumin - chemistry; Sesquiterpenes - pharmacology; Time Factors; Tritium; deferoxamine; electrospray ionization-mass spectra; DTNB; NEM; IA; succinic anhydride; ESI-MS; iodoacetamide; DFO; SA; N-ethyl-maleimide; 5,5'-dithionitrobenzoic acid; Human; Antimalarial; Biological fixation; Serum albumin; Mechanism of action; In vitro; Alkylation
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/0006-2952(93)90425-V

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 Fe 2+ 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.