title: The apicoplast: a key target to cure malaria.
abstract: Malaria is one of the major global health problems. About 500 million humans are infected each year, and 1 million, mostly African children, die from malaria annually. No vaccine is yet in sight, and those drugs that have previously served us well are now losing ground against the disease as parasites become resistant to our best compounds. The need for development of new antimalarials is now more urgent than ever. An exciting avenue for development of new drugs emerged recently when it was discovered that the malaria parasites have a previously unrecognized evolutionary history aligned to plants. These parasites contain a subcellular compartment--the apicoplast--which is homologous to the chloroplast of plants and algae, in which photosynthesis occurs. The malaria chloroplast (apicoplast) has lost photosynthesis but it retains many chloroplast pathways, which are otherwise unique to plants. These pathways obviously do not exist in the human host and there has been considerable excitement about using the apicoplast as a parasite-specific Achilles' Heel. We propose to review the current state of development of novel compounds directed against this emerging target of malaria parasites with emphasis on the chemistry.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: James I
authors.initials: JI
authors.lastname: MacRae
authors.forename: Eric
authors.initials: E
authors.lastname: Maréchal
authors.forename: Christophe
authors.initials: C
authors.lastname: Biot
authors.forename: Cyrille Y
authors.initials: CY
authors.lastname: Botté
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000378:metabolism* / Q000469:parasitology; D010788:Photosynthesis / Q000187:drug effects*; D010965:Plasmodium malariae / Q000187:drug effects*; D018087:Plastids / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000962:Antimalarials