Chloroquine and artemisinin: six decades of research--what next?

Over the next decade drugs will remain the focus of continuous efforts to control malaria, with a contribution from pharmacogenomic development. Quinine, extracted from Cinchona bark, has been the source for aminoquinoline drugs such as chloroquine; more recently, artemisinin extracted from Artemisia allowed the design of artemisinin mimics containing a trioxane structure. Here, we examine parallels between chloroquine and artemisinin in terms of pharmacological target discovery, mechanism of action and parasite resistance. The widespread use of chloroquine has dramatically reduced its therapeutic response, thus recent strategies are based on artemisinin combinations.