Ferryl-oxo heme intermediate in the antimalarial mode of action of artemisinin
Language: 
English
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 nu(O-O) and nu(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 (18)O-O(18) endoperoxide enriched trioxane alcohol. The frequency of this vibration and the magnitude of the (18)O-O(18) 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.

Author(s): 
Kapetanaki, S.
Varotsis, C.
Item Type: 
Journal Article
Publication Title: 
FEBS letters
Journal Abbreviation: 
FEBS Lett.
Publication Date: 
6/2/2000
Publication Year: 
2000
Pages: 
238-241
Volume: 
474
Issue: 
2/3/2015
ISSN: 
0014-5793
Library Catalog: 
PubMed
Extra: 
PMID: 10838092

Turabian/Chicago Citation

S. Kapetanaki and C. Varotsis. 6/2/2000. "Ferryl-oxo heme intermediate in the antimalarial mode of action of artemisinin." FEBS letters 474: 2/3/2015: 238-241.

Wikipedia Citation

<ref> {{Cite journal | doi = | issn = 0014-5793 | volume = 474 | pages = 238-241 | last = Kapetanaki | first = S. | coauthors = Varotsis, C. | title = Ferryl-oxo heme intermediate in the antimalarial mode of action of artemisinin | journal = FEBS letters | date = 6/2/2000 | pmid = | pmc = }} </ref>