Please use this identifier to cite or link to this item:
|Title:||Ferryl–oxo heme intermediate in the antimalarial mode of action of artemisinin||Authors:||Kapetanaki, Sofia M.
|Keywords:||Antimalarials;Artemisinin;Fourier transform infrared spectroscopy;Heme;Iron;Oxygen;Raman spectrometry||Issue Date:||2000||Publisher:||Elsevier||Source:||FEBS letters, 2000, Volume 474, Issues 2–3, Pages 238–241||Abstract:||Fourier transform infrared (FTIR) and resonance Raman (RR) spectroscopies have been employed to investigate the reductive cleavage of the O-O bond of the endoperoxide moiety of the antimalarial drug artemisinin and its analog trioxane alcohol by hemin dimer. We have recorded FTIR spectra in the ν(O-O) and ν(as)(Fe-O-Fe) regions of artemisinin and of the hemin dimer that show the cleavage of the endoperoxide and that of the hemin dimer, respectively. We observed similar results in the trioxane alcohol/hemin dimer reaction. The RR spectrum of the artemisinin/hemin dimer reaction displays a vibrational mode at 850 cm-1 that shifts to 818 cm-1 when the experiment is repeated with 18O-O18 endoperoxide enriched trioxane alcohol. The frequency of this vibration and the magnitude of the 18O-O18 isotopic shift led us to assign the 850 cm-1 mode to the Fe(IV) = O stretching vibration of a ferryl-xoxo heme intermediate that occurs in the artemisinin/hemin dimer and trioxane alcohol/hemin reactions. These results provide the first direct characterization of the antimalarial mode of action of artemisinin and its trioxane analog, and suggest that artemisinin appears to react with heme molecules that have been incorporated into hemozoin and subsequently the heme performs cytochrome P450-type chemistry||URI:||http://ktisis.cut.ac.cy/handle/10488/6665||ISSN:||00145793||DOI:||10.1016/S0014-5793(00)01592-1||Rights:||© 2000 Federation of European Biochemical Societies||Type:||Article|
|Appears in Collections:||Άρθρα/Articles|
Show full item record
checked on Feb 13, 2018
WEB OF SCIENCETM
checked on Sep 14, 2019
Page view(s) 5075
checked on Sep 15, 2019
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.