Design, Synthesis and Antimalarial/anticancer Evaluation of Spermidine Linked Artemisinin Conjugates Designed to Exploit Polyamine Transporters in Plasmodium Falciparum and HL-60 Cancer Cell Lines

A series of artemisinin-spermidine conjugates designed to utilise the upregulated polyamine transporter found in cancer cells have been prepared. These conjugates were evaluated against human promyelocytic leukaemia HL-60 cells and chloroquine-sensitive 3D7 Plasmodium falciparum and several show promising anticancer and antimalarial activity. Although some limitations in this vector-based approach are apparent, a number of high potency Boc-protected analogues were identified with activity against malaria parasites as low as 0.21nM.