Anticancer drugs plant derivatives

Another area in which natural products have had a major impact on longevity and quality of life is in the chemotherapy of cancer (see Chapter 62). In fact, most major anticancer drugs are derived from plants or microorganisms. Important examples include bleomycin, doxorubicin, daunorubicin, vincristine, vinblastine, mitomycin, streptozocin, and most recently, paclitaxel... 

Approximately 60% of the world s population relies almost entirely on plants for medication. Natural products have long been recognized as an important source of therapeutically effective medicines. Of the 520 new drugs approved between 1983 and 1994, 39% were natural products or derived from natural products. Sixty percent to 80% of antibacterials and anticancer drugs were derived from natural products. 

Amin A, Gali-Muhtasib H, Ocker M, Schneider-Stock R. (2009) Overview of major classes of plant-derived anticancer drugs. Int J Biomed Sci 5 1-11. 

In recent years, however, some of the greatest emphasis has been placed on the search for anticancer and antiviral agents derived from natural products. Success in that area has not heen as great as that achieved in other helds. Since 1960, only seven plant-derived drugs have heen approved by the FDA for use as anticancer agents. Four of those drugs, vinblastine, vincristine, etoposide, and teniposide, were discovered in the 1950s. The last three—Taxol , topotecan, and irinotecan—were discovered and approved much more recently. 

As will be mentioned further in this chapter, the discovery of the anticancer drug, paclitaxel (21), was soon followed by sourcing issues due to the low yield of this compound in the source plant, Taxus brevifolia Nutt. This led to the semisynthesis of paclitaxel (21), from a precursor molecule, 10-deacetylbaccatin III, readily available from the leaves of Taxus baccata L., a renewable source with high yields of this compound.Docetaxel (37) is a second taxane class anticancer drug and is a semisynthetic derivative of paclitaxel (21). ... 

The result of nondisjunction, loss of one chromosome, for example, may be incompatible with survival of the cell, so aneugens are often cytotoxic. This obviously only occurs in cells, which are actively dividing, therefore such compounds find use as anticancer drugs. Two examples are vincristine and vinblastine, two vinca alkaloids, derived from a plant. 

Since 1961, nine plant-derived compounds have been approved for use as anticancer drugs in the U.S. vinblastine (Velban), vincristine (Oncovin), etoposide (VP-16,1), teniposide... 

The mitotic spindle is part of a larger intracellular skeleton (cytoskele-ton) that is essential for the internal movements occurring in the cytoplasm of all eukaryotic cells. The mitotic spindle consists of chromatin, and a system of microtubules composed of the protein tubulin. The mitotic spindle is essential for the equal partitioning of DNA into the two daughter cells formed when a eukaryotic cell divides. Several plant-derived substances used as anticancer drugs disrupt this process by affecting the equilibrium between the polymerized and depolymerized forms of the microtubules, thereby causing cytotoxicity. 

The contribution of plants to modern medicine can hardly be overstated. Many plant natural products are used in medicine in their native, undomesticated form and the anti-Alzheimer s alkaloid galanthamine and the anticancer diterpenoid paclitaxel are additions to the inventory of plant-derived drugs obtained by direct isolation.101... 

A variety of plant substances with planar, polycyclic, aromatic structures can intercalate with DNA, examples being the quinoline alkaloid camptothecin and the furanocoumarin phenolic psoralen (Table 12.1). A variety of plant-derived anthraquinones and naphthoquinones bind to DNA and it is notable that the structurally related anthraquinones mitox-antrone and adriamycin are clinically employed as anticancer drugs (Table 12.1). DNA-binding compounds that interfere with DNA repair, DNA replication and gene expression are cytotoxic and have potential as anticancer agents (see Chapter 9). 

The MDR transporter is of importance in drug resistance in antiprotozoal and anticancer chemotherapy and hence compounds that inhibit this transporter are potentially very useful as adjuncts to chemotherapy to overcome such drug resistance (Table 13.7). This chapter also deals with numerous plant-derived compounds that inhibit various other enzymes (Table 13.8). 

Higher plants have yielded many effective, clinically useful anticancer drugs, including those derived from Catharanthus alkaloids, Taxus diterpenes, Camptotheca alkaloids, and Podophyllum lignans. Research in this area has been reviewed extensively (3-13). 

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... 

Plant cells Used to make pharmaceuticals currently derived from plants (25% of all pharmaceuticals currently extracted from plants) Food flavors, fragrances, insecticides dyes TaxoF —anticancer drug Slow growth Plant genetics poorly understood Products are often not proteins and chemically complex Expensive to culture so need high-value products like Taxol... 

The discovery that several major anticancer drugs, originally isolated from plants, are produced by associated endophytic fungi (Section III.B.3.) opens up further avenues for exploring the large-scale production of plant-derived pharmaceuticals. Likewise, the probable role of microbial symbionts in the production of bioactive agents from marine macroorganisms (Section III.B.4.) offers... 

Important drugs have been derived from two plants common in the woodlands of the eastern United States. One is etoposide (an anticancer drug) based on the podophyllotoxin found in Podophyllum peltatum,415 The second is sanguinarine (from Sangulnarla canadensis), which is used for treatment of periodontal disease. A common fence lizard of the western United States, Sceloporus occidentalis, has something in the blood that kills the bacteria responsible for Lyme disease.416... 

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. 

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