Antimalarial activity of artemisinin

Jones M, Mercer AE, Stocks PA, La Pensee LJ, Cosstick R, Park BK, Kennedy ME, Piantanida 1, Ward SA, Davies J, Bray PO Rawe SL, Baird J, Charidza T, Janneh O, O Neill PM. (2009) Antitumor and antimalarial activity of artemisinin-acridine hybrids. Bioorg Med Chem Lett 19 2033-2037. 

In Vitro Neurotoxicity and Antimalarial Activity of Artemisinin Analogs... 

Posner, G.H. and Oh, C. A regiospecifically oxygen-18 labeled 1,2,4-trioxane a simple chemical model system to probe the mechanism(s) for the antimalarial activity of artemisinin (Qinghaosu), /. Am. Chem. Soc., 114, 8328,1992. 

Cumming, J. N. Posner, G. H. Antimalarial activity of artemisinin (qinghaosu) and related trioxanes Mechanism(s) of action. Adv. Pharmacol. San Diego), 1997, 37 253-297. 

Whole plant extracts often show promising activity that may not be traceable to single components. This is obviously not true of Artemisia annua extracts, but it is interesting to note that other constituents, notably me-thoxylated flavones, have potentiating effects on the antimalarial activity of artemisinin (206). 

Drug activation by iron and heme may explain why endoperoxides are selectively toxic to malaria parasites. The malaria parasites live in a milieu of heme iron, which the parasite converts into insoluble hemozoin. Chloroquine, which binds heme, antagonizes the antimalarial activity of artemisinin. 

Although the antimalarial activity of artemisinin has been attributed to its... 

Summing JN, Ploypradith P, Posner GH. Antimalarial activity of artemisinin (Qinghaosu)... 

Modeling the decomposition mechanism of artemisinin at Hartree-Fock (HF) and DFT theoretical levels supported the current hypothesis that some of the stable neutral intermediates and radical anions could be responsible for the antimalarial activity of artemisinin derivatives <2006BMC1546, 2006PCA7144, 2006JME6065>. 

Due to the unabated interest in the antimalarial activity of artemisinin 17 and its derivatives, the synthesis of 1,2,4-trioxanes has been studied intensively a comprehensive overview is given in CHEC-II(1996). Developed methods have been applied continuously and a survey of synthetic paths from 1996 onward is presented below. 

Isolated in 1971, artemisinin has recently been widely used in Asia for the treatment of malaria. It has been suggested that intraparasitic hemin (Figure 3-34b) mediates the antimalarial activity of artemisinin. Malaria parasites contain precipitated hemin, known as hemozoin. In vivo, a reaction between hemin and artemisinin appears to generate free radicals, some of which appear to alkylate hemin. °... 

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