Synthesis and anti-cancer activity of covalent conjugates of artemisinin and a transferrin-receptor targeting peptide

Artemisinin, a natural product isolated from Artemisia annua L., shows a unique anti-cancer activity by an iron dependent mechanism. Artemisinin was covalenty conjugated to a transferrin-receptor targeting peptide, HAIYPRH that binds to a cavity on the Surface Of transferrin receptor. This enables artemisinin to lie co-internalized with receptor-bound transferrin. The iron released from transferrin can activate artemisinin to generate toxic radical species to kill cells. The artemisinin-peptide conjugates showed potent anti-cancer activity against Molt-4 leukemia cells with a significantly improved cancer/normal cells selectivity. (c) 2008 Elsevier Ireland Ltd. All rights reserved.