ABSTRACT
The antimalarial activity of a number of artemisinin derivatives, both newly synthesized and currently used as drugs, against Plasmodium falciparum in culture shows a correlation with their affinity of binding with ferroprotoporphyrin IX, as measured from the spectral change of the latter. The new C-16-functionalized artemisinin derivatives were obtained through a novel one-pot synthesis of artemisitene (2) from naturally abundant artemisinin (1), followed by Michael addition with nucleophiles. 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 similar structures.
Subject(s)
Antimalarials/chemical synthesis , Antimalarials/pharmacology , Artemisinins , Heme/metabolism , Plasmodium falciparum/drug effects , Sesquiterpenes/pharmacology , Animals , Cells, Cultured , Magnetic Resonance Spectroscopy , Molecular Structure , Sesquiterpenes/chemical synthesis , Sesquiterpenes/metabolismABSTRACT
Various derivatives of artemisinin covalently linked to iron chelators were synthesized, and their antimalarial activities were evaluated. Although results show no indication that the presence of an iron chelator in the vicinity of artemisinin potentiates its action, the linked compounds prepared still retain comparable activities to that of artemisinin.
