Interaction of artemisinin based antimalarial drugs with hemin in water-DMSO mixture

The interaction of hemin with artemisinin, artesunate and dihydroartemisinin was investigated by UV-Visible Spectroscopy at pH 9 and High Performance Liquid Chromatography/Diode Array Detector/Mass Spectrometry (HPLC/DAD/MS) for their reactivity with hemin. It has been showed that artesunate and dihydroartemisinin interacted more strongly with Fe (III) PPIX that artemisinin did. The reported results showed too that hemin and endoperoxide lactone derived antimalarials slowly react to give rise to several stereoisomers supramolecular adducts (three for artesunate, seven for artemisinin and eight isomers for dihydroartemisinin) while in contrast, only heme (Fe2) was found to react with artemisinin based drugs in previous studies. Based on this result, our work confirmed the mechanism in which the artemisinin derivates approach hemin by pointing O1 at the endoperoxide linkage toward iron center, a mechanism that is controlled by steric hindrance. After that C3-C4 bond is cleaved to give rise carbon radical at C4 as predicted by automated calculation of docking of artemisinin to heme. © 2007 Asian Network for Scientific Information.