TY - JOUR
T1 - The reaction of artemisinins with hemoglobin
T2 - A unified picture
AU - Messori, Luigi
AU - Gabbiani, Chiara
AU - Casini, Angela
AU - Siragusa, Matteo
AU - Vincieri, Franco Francesco
AU - Bilia, Anna Rita
N1 - Funding Information:
The Ente Cassa di Risparmio di Firenze is gratefully acknowledged for financial support.
PY - 2006/5/1
Y1 - 2006/5/1
N2 - 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.
AB - 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.
KW - Artemisinin
KW - Hemoglobin
KW - Malaria
UR - http://www.scopus.com/inward/record.url?scp=33644980165&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2005.12.038
DO - 10.1016/j.bmc.2005.12.038
M3 - Article
C2 - 16412643
AN - SCOPUS:33644980165
SN - 0968-0896
VL - 14
SP - 2972
EP - 2977
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 9
ER -