title: The antimalarial drug artemisinin alkylates heme in infected mice.
abstract: Heme alkylation by the antimalarial drug artemisinin is reported in vivo, within infected mice that have been treated at pharmacologically relevant doses. Adducts resulting from the alkylation of heme by the drug were characterized in the spleen of treated mice, and their glucuroconjugated derivatives were present in the urine. Because these heme-artemisinin adducts were not observed in noninfected mice, this report confirms that the alkylating activity of this antimalarial drug is related to the presence of the parasite in infected animals. The identification of heme-artemisinin adducts in mice should be considered as the signature of the alkylation capacity of artemisinin in vivo.
authors.affiliation: Laboratoire de Chimie de Coordination du Centre National de la Recherche Scientifique, 205 Route de Narbonne, 31077 Toulouse Cedex 4, France. arobert@lcc-toulouse.fr
authors.forename: Anne
authors.initials: A
authors.lastname: Robert
authors.forename: Françoise
authors.initials: F
authors.lastname: Benoit-Vical
authors.forename: Catherine
authors.initials: C
authors.lastname: Claparols
authors.forename: Bernard
authors.initials: B
authors.lastname: Meunier
mesh_terms: D000478:Alkylation; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000032:analysis*; D037621:Artemisinins / Q000008:administration & dosage / Q000032:analysis*; D005260:Female; D006418:Heme / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism; D008288:Malaria / Q000188:drug therapy / Q000652:urine; D051379:Mice; D010961:Plasmodium; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000032:analysis*; D013154:Spleen / Q000737:chemistry* / Q000378:metabolism / Q000469:parasitology; D014556:Urine / Q000737:chemistry
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D006418:Heme; C031327:artemisinin