Evidence that the antimalarial activity of artemisinin is not mediated via intercalation with nucleotides.

Abstract

The interaction of artemisinin, a new sesquiterpine lactone antimalarial drug, with some target macromolecules represented by calf thymus deoxyribonucleic acid (DNA) and the dinucleotide guanylyl (3----5) cytidine (GpC) was studied by 1H-NMR. There was no intercalation between artemisinin and DNA or GpC as judged by the lack in change of chemical shifts (delta delta) or coupling constants (delta J) of the C-13, C-14, and C-15 methyl groups of artemisinin. This conclusion was substantiated by studying the optical rotatory dispersion (ORD) between artemisinin and these target macromolecules. It is suggested that artemisinin exerts its antimalarial action via a mechanism different from that of the aminoquinolines antimalarial agents, possibly through the peroxygen linkage which is essential for artemisinin biological activity.