Alkylation of human hemoglobin A0 by the antimalarial drug artemisinin.
In vitro, the heme cofactor of human iron(II) hemoglobin was efficiently and quickly alkylated at meso positions by the peroxide-based antimalarial drug artemisinin, leading to heme-artemisinin-derived covalent adducts. This reaction occurred in the absence of any added protease or in the presence of an excess of an extra non-heme protein, or even when artemisinin was added to hemolysed human blood. This activation of artemisinin by the heme moiety of non-digested hemoglobin clearly indicates the high affinity of this drug for heme, and its efficient alkylating ability under very mild conditions.
Selmeczi
Katalin
K
Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Cedex 4, Toulouse, France.
Robert
Anne
A
Claparols
Catherine
C
Meunier
Bernard
B
D000478:Alkylation; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D037621:Artemisinins / Q000737:chemistry* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006418:Heme / Q000737:chemistry; D006441:Hemoglobin A / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D010108:Oxyhemoglobins / Q000737:chemistry* / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization
D000962:Antimalarials; D037621:Artemisinins; D010108:Oxyhemoglobins; D012717:Sesquiterpenes; D006418:Heme; D006441:Hemoglobin A; C029774:oxyhemoglobin A; C031327:artemisinin