Malaria artemisinin

Besides their essential roles in nature, isoprenoids are of commercial importance in industry. Some isoprenoids have been used as flavors, fragrances, spices, and food additives, while many are used as pharmaceuticals to treat an array of human diseases, such as cancer (Taxol), malaria (artemisinin), and HIV (coumarins). In contrast to the huge market demand, isoprenoids are present only in low abundance in their host organisms. Thus, isolation of the required isoprenoids consumes a large quantity of natural resources. Furthermore, owing to their structural complexity, total chemical synthesis is often not commercially feasible. For these reasons, metabolic engineering may provide an alternative to produce these valuable isoprenoids [88,89]. 

Artemisinin, a tetracyclic 1,2,4-trioxane isolated from Artemisia annua L., is currently recommended as a first-line agent against Plasmodium falciparum malaria. Artemisinin and its synthetic derivatives have also been shown to be promising prototypes for the development of new antiproliferative agents. This chapter presents the recent advances on the analytic methods for extraction and quantification of artemisinin from A. annua plants as well as the biological properties of this natural product. 

Qinghao (Sweet Wormwood) is the dried aerial parts of the herb Artemisia annua L. (Asteraceae family), which has been used in China for centuries to treat fever and malaria. Artemisinin (Nl) (Qing Hao Su) (128), the active principle, directly kills Plasmodium falciparum (malaria parasites) with little toxicity to animals and humans. Thus, it is a clinically effective, safe, and rapid antimalarial agent (129, 130). The novel endo-peroxide link is essential for the antimalarial activity. 

Phosphorus ylides C-substituted and stabifized by elements of group 16 are often used for the synthesis of natural substances. For example, the synthesis of simpHfied analogs of artemisinin, used against chloroquine-resistant malaria, has been recently described from methoxymethylphosphonium yhde 120 [127,128]. The later is able to convert afiphatic nitriles into a-functionafized ketones 122 which are the precursors of the target compounds. Starting from the aromatic ni-... 

There is an expanding body of evidence to suggest that sesquiterpene lactones inhibit the synthesis NO synthetase. One such compound is an ambrosanolides-type sesquiterpene known as cumanin characterized from Ambrosia psilostachya. This sesquiterpene inhibit the enzymatic activity of NO synthetase with an IC50 value of 9.38 xM (49). Another example is the well-known artemisinin, a sesquiterpene used as an alternative drug in the treatment of severe and multidrug-resistant malaria, which inhibits NO synthesis in cytokine-stimulated human astrocytoma T67 cells (50). 

How do traditional remedies fare in such trials Some perform quite well and prove to be highly effective, but others are no better than placebos. One striking success is an extract of sweet wormwood (Artemisia annua), which Chinese physicians have prescribed for the chills and fevers of malaria for more than two thousand years. About twenty-five years ago, Chinese chemists obtained from sweet wormwood its principal active component, a compound now called artemisinin. Clinical trials on malaria patients in Southeast Asia agreed with Chinese tradition on the value of artemisinin and also identified a few even more useful drugs prepared from it in the laboratory. These compounds are effective against the deadliest form of malaria and are now frequently the therapies of choice for treating it. 

The Plasmodium falciparum malaria PD model successfully described the antimalarial effect of artemisinin, mefloquine, and a combination of the two drugs... 

Svensson, U.S., Alin, H., Karlsson, M.O., Bergqvist, Y., and Ashton, M., Population pharmacokinetic and pharmacodjmamic modeling of artemisinin and mefloquine enantiomers in patients with falciparum malaria, Eur.. Clin. Pharmacol, 58, 339-351, 2002. 

Key Natural Products in Malaria Chemotherapy From Quinine to Artemisinin and Beyond... 

Since that time, artemisinin has been used successfully in many thousand malaria patients throughout the world including those infected with both cldoroquine-sensitive and chloroquine-resistant strains of P falciparum. Artemisinin has progressively estabhshed itself as one of the most potent and effective antimalarial dmg, and is primarily recommended in the treatment of multidrug-resistant strains of P. falciparum. However, the therapeutic... 

It is clear that no other compound or family of compounds have affected the chemotherapy of malaria as much as quinine and its derivatives, and artemisinin and its derivatives. Nevertheless, there are some classes of natural products that have made it to the market or at least at the advanced stage of clinical trials as antimalarial. Among them are quinones, chalcones and xanthones. 

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