The reaction of artemisinins with hemoglobin: A unified picture

Luigi Messori, Chiara Gabbiani, Angela Casini, Matteo Siragusa, Franco Francesco Vincieri, Anna Rita Bilia

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

The reactions with hemoglobin of artemisinin and of its parent compounds, sodium artesunate and dihydroartemisinin, were investigated by visible absorption spectroscopy under standard solution conditions (50 mM phosphate buffer, pH 7, 37°C). Notably, these antimalarial drugs were found to react with hemoglobin (i.e., ferrous heme), but not with methemoglobin (i.e., ferric heme). The reaction selectively occurs at the heme sites and consists of the progressive, slow decay of the Soret band, as a consequence of heme alkylation and subsequent loss of π electron delocalization. For the various tested compounds the process reaches completion within ∼30-70 h. Additional experiments were carried out upon adopting the solution conditions described by Meunier et al. and by Kannan et al. in their recent studies. Some reactivity of artemisinin with methemoglobin was indeed detected after addition of 50% v/v acetonitrile, most likely as a consequence of extensive protein unfolding. A unified description for the reactions of artemisinins with hemoglobin is given.

Original languageEnglish
Pages (from-to)2972-2977
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number9
DOIs
StatePublished - 1 May 2006
Externally publishedYes

Keywords

  • Artemisinin
  • Hemoglobin
  • Malaria

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