Plant-derived drugs artemisinin

From a historical perspective, the first analogues were semisynthetic derivatives of artemisinin itself, which had been isolated in modest amounts from plants. Despite these early limitations, several of these analogues have now achieved clinical utility because their structural alterations provide improved drug delivery characteristics. These analogues retain the entire tetracyclic structure and incorporate pendant substituents. By comparison to these early analogues, our total... 

Traditional Chinese Medicine gave rise to new plant-derived anticancer drugs as well as to therapeutics for the treatment of drug-resistant types of malaria tropica [70]. Artemisinin (Qinghaosu), the bioactive principle of Artemisia annua, was identified in 1972. Its unique structure was proven by X-ray analysis... 

The study of natural products, or Nature s Combinatorial Library , has had a long history as a source of drugs, and plants have historically been at the forefront of natural product drug discovery. In the anticancer area, for example, vinblastine and vincristine, etoposide, paclitaxel (Taxol), docetaxel, topotecan, and irinotecan, among others, are all plant-derived natural products or modified versions of plant compounds, while antimalarial therapy would be much poorer without quinine and artemisinin and the drugs derived from these plant products. This chapter provides an overview of the major medicinal agents that are themselves natural products isolated from plants or are chemical modifications of such lead compounds. It covers the therapeutic areas of cancer, HIV, malaria, cardiovascular, and central nervous system (CNS) diseases. Natural plant products have also made contributions in areas such as immunomodulatory and antibiotic activities," and the reader is referred to the cited reviews for information on these areas. 

Artemisinin (qinghaosu) provides a more recent example of a plant-derived antimalarial agent. Based on the reputed antimalarial use of Artemisia annua in the Chinese system of traditional medicine, artemisinin was isolated from the plant as the active compound, developed as a drug, and released for clinical use as a blood schizonticide (66-68). Artemisinin is a... 

With over 250,000 species, the plant kingdom contains biodiversity which reflects known and novel compounds with potential therajjeutic activity (2,82,83). Furthermore, the World Health Organization has estimated that 80% of people in developing countries are dependent upon plant-centered traditional medicines for their primary health care (84). The examples of quinine and artemisinin cited above illustrate the proven utility of compounds from plants in the treatment of malaria. Moreover, it is likely that additional plant-derived antimalarial drugs await discovery since the literature indicates that in vivo or in vitro antimalarial activities have been identified in a broad and varied spectrum of botanical families (85-92). 

Among the worldwide total of 30000 known natural products, about 80% stems from plant resources. The number of known chemical structures of plant secondary metabolites is four times the number of known microbial secondary metabolites. Plant secondary metabolites are widely used as valuable medicines (such as paclitaxel, vinblastine, camptothecin, ginsenosides, and artemisinin), food additives, flavors, spices (such as rose oil, vanillin), pigments (such as Sin red and anthocyanins), cosmetics (such as aloe polysaccharides), and bio-pesticides (such as pyrethrins). Currently, a quarter of all prescribed pharmaceuticals compounds in industrialized countries are directly or indirectly derived from plants, or via semi-synthesis. Furthermore, 11% of the 252 drugs considered as basic and essential by the WHO are exclusively derived from plants. According to their biosynthetic pathways, secondary metabolites are usually classified into three large molecule families phenolics, terpenes, and steroids. Some known plant-derived pharmaceuticals are shown in Table 6.1. 

Natural products have been used as therapeutic agents or medicinal products for millennia in one form or another and a huge number of these, especially prior to the last 50 years, are derived from plants [2]. Today, natural products derived from plant sources continue to play a vital role in the treatment of diseases. There are many examples where the active compound in plant-derived traditional medicines has been used as a pharmaceutical agent. A particularly important example is the discoveiy and development of anti-malarial drugs such as quinine and artemisinin (Fig. 1.3). Quinine was isolated as early as 1820 and was used extensively until the... 

The other natural compound and its derivatives that are now being widely constituted into anti-malarial drugs is artemisinin. This compound was isolated from the age-old Chinese anti-malarial drug, qinq hao su, isolated from the plant qinq hao or Artemisia annua, which is now a widely grown crop in Kenya and East Africa in general. Artemisinin is an excellent anti-plasmodial whose derivatives are now being constituted as artemisinin combination therapy drugs (ACTs) by different companies. An example of an ACT is Coartem, a combination of artemether and lumefantrine, from Novartis. 

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