Free Radical Cleavage Of Artemisinin Ether Bridged Dimer Derivatives

This thesis reviewed the exploits and the antimalarial mechanisms of artemisinin-type drugs. Strong interest has been directed at the dual medicinal value of 1, 2, 4-trioxanes and trioxane dimers as both antimalarial and especially antitumor agents. Here we selected ether-linked dimers of dihydroartemisinin with high activities and simple structures to prepare. We obtained and characterized the dimer of dihydroartemisinin by single crystal X-ray diffraction which has α and β-arteether moieties linked via an O bridge, so that the molecule is asymmetric about the O bridge. Comparing the two reactions: ferrous iron in the presence of cysteine cleaved the peroxy bonds of the dimmer and ferrous iron cleaved the peroxy bonds of the dimmer, we try to explain how and why the dimers of dihydroartemisinin retained the endoperoxide bridges have both antimalarial and antitumor activity from the reaction mechanism. The mode of action to cleave the peroxy bond into free radicals maybe explains antimalarial and antitumor activities of the dimer of the dihydroartemisinin from molecules level. The result may provide a support for research of structure-function relation and exploitation of new antimalarial drugs.