Natural products anticancer drug leads

Although serendipity is not a reliable source of new anticancer-drug leads, more molecules with interesting anticancer properties might still appear through chance in the future, especially from natural products. Second, synthetic chemistry has been used to modify drug leads discovered in plant material - the so-called semi-synthetic approach. 

Kinghom AD, Chin Y-W, Swanson SM (2009) Discovery of natural product anticancer agents from biodiverse organisms. Curr Opin Drug Discov Dev 12 189-196 Newman DJ (2008) Natural products as leads to potential dmgs an old process or the new hope for drug discovery J Med Chem 51 2589-2599... 

In many cases the isolated natural product may not be an effective drug for any of several possible reasons, but it may nevertheless have a novel pharmacophore. In such cases chemical modification of the natural product structure, either by direct modification of the natural product (semisynthesis) or by total synthesis, can often yield clinically useful drugs. Examples of this from the anticancer area are the drugs etoposide, teniposide, and topote-can, derived from the lead compounds podophyllotoxin and campothecin. 

No other single phylum has been more productive than that of the marine Porifera in producing leads for drug discovery and molecular tools. The remarkable activity of the cytotoxic compounds 1-19 (Scheme 6.1 Parts 1 and 2) have led to the development of marine natural products and their congeners as leads in numerous anticancer clinical trials. The actin inhibitors 20-26 (Scheme 6.1 Part 3) have led to the use of sponge-derived agents as probes in the study of cellular processes. In addition, a number of unique structures such as 27-31 (Scheme 6.1 Part 4) have potential as leads in the treatment of other persistent maladies such as asthma, pain and malaria. 

Natural products have played a much bigger role, perhaps second only to antibacterial agents, in the discovery and development of anticancer agents either directly as drugs or leads to... 

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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