The Apicoplast: A Key Target to Cure Malaria

James      I. MacRae; Eric      Marechal; Christophe      Biot; Cyrille      Y. Botte

doi:10.2174/138161212801327275

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.

Keywords: Apicomplexa, apicoplast, secondary plastid, fosmidomycin, malaria, vaccine, chloroplast pathways, parasite-specific Achilles’ Heel, chloramphenicol, apicomplexan parasites