The future of antimalarials: Artemisins and synthetic endoperoxides

Abstract

Malaria is one of the most widespread infectious diseases in the world. Plasmodium falciparum, the main strain responsible for human malaria, has developed resistance to most available antimalarial agents. Artemisinin isa sesquiterpenic lactone isolated from Artemisia annua L., a plant used in traditional Chinese medicine. It is very effective in treating drug-resistant malaria and appears very promising for fighting the disease. Numerous investigations are currently being performed with the aim of elucidating the mechanism of action, determining efficient clinical uses and discovering new drugs with better pharmacological properties. Most investigations revolve around the highly unusual endoperoxide present in artemisinin, which is responsible for the antimalarial activity. Several strategies have been developed for the design of semisynthetic and synthetic endoperoxides with greater metabolic and hydrolytic stability than artemisinin itself. Here we present an overview of this area.