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Expert Rev Anti Infect Ther. 2009 Oct;7(8):999-1013. doi: 10.1586/eri.09.68.

Discovery, mechanisms of action and combination therapy of artemisinin.

Author information

1
Department of Entomology, Pennsylvania State University, University Park, PA 16802, USA. luc2@psu.edu

Abstract

Despite great international efforts, malaria still inflicts an enormous toll on human lives, especially in Africa. Throughout history, antimalarial medicines have been one of the most powerful tools in malaria control. However, the acquisition and spread of parasite strains that are resistant to multiple antimalarial drugs have become one of the greatest challenges to malaria treatment, and are associated with the increase in morbidity and mortality in many malaria-endemic countries. To deal with this grave situation, artemisinin-based combinatory therapies (ACTs) have been introduced and widely deployed in malarious regions. Artemisinin is a new class of antimalarial compounds discovered by Chinese scientists from the sweet wormwood Artemisia annua. The potential development of resistance to artemisinins by Plasmodium falciparum threatens the usable lifespan of ACTs, and therefore is a subject of close surveillance and extensive research. Studies at the Thai-Cambodian border, a historical epicenter of multidrug resistance, have detected reduced susceptibility to artemisinins as manifested by prolonged parasite-clearance times, raising considerable concerns on resistance development. Despite this significance, there is still controversy on the mode of action of artemisinins. Although a number of potential cellular targets of artemisinins have been proposed, they remain to be verified experimentally. Here, we review the history of artemisinin discovery, discuss the mode of action and potential drug targets, and present strategies to elucidate resistance mechanisms.

PMID:
19803708
PMCID:
PMC2778258
DOI:
10.1586/eri.09.68
[Indexed for MEDLINE]
Free PMC Article
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