CORRELATION OF ANTIMALARIAL ACTIVITY OF ARTEMISININ DERIVATIVES WITH BINDING-AFFINITY WITH FERROPROTOPORPHYRIN-IX

The antimalarial activity of a number of artemisinin derivatives, both newly synthesized and currently used as drugs, against Plasmodium fal ciparum in culture shows a correlation with their affinity of binding with ferroprotoporphyrin IX, as measured from the spectral change of t he latter. The new C-le-functionalized artemisinin derivatives were ob tained through a novel one-pot synthesis of artemisitene (2) from natu rally abundant artemisinin (1), followed by Michael addition with nucl eophiles. The correlation points to the biological significance of the interaction of these derivatives with ferroprotoporphyrin IX and may provide a basis for primary screening of peroxidic antimalarials of si milar structures.