Medicines from the Rainforest: Biodiversity and Biologically Active Natural Products
As immobile organisms, plants must defend themselves by thwarting or injuring their predators, from microorganisms to bacteria, to animals or other plants. To do so, plants have developed complex chemical defenses including many chemically diverse compounds. This diversity results in many novel bioactive secondary metabolites with therapeutic potential. As DH Williams notes, “all natural products have evolved under the pressure of natural selection to bind to specific receptors” (Cutler, 41).
Some examples of over fifty natural products or natural product-derived drugs are in cardiovascular treatment, mevastatin, isolated from a Penicillium sp. Culture, and the analogs of this drug, lovastatin and simvastatin. Natural antiinfective agents include penicillins, cephalosporins, and vancomycins. The anitmalarial drug quinine is most effective, and many analogs have been developed to treat malaria. Microbial products cyclosporin and rapamycin are effective immunosuppressants. Several alkaloids have proven therapeutically beneficial, such as ergoline and terguride, both inhibitors of prolactin secretion, and huperzine, isolated from club moss, which has proven effective against cholinergic-related neurodegenerative disorders like Alzheimer’s disease. The anticancer area, in particular, has made great use of natural products such as vinblastine and vincristine (vinca alkaloids), etoposide and teniposide (podophylltoxin analogues), paclitaxel (Taxolä), and camptothecin –derived topotecan. In the past ten years, 62% of the new anticancer-agents have been natural products or based on natural product models.
One reason why natural products are advantageous is that they provide complex molecules not accessible through synthesis. For example, Taxol and rapamycin could not be synthesized by standard medicinal chemistry, even including combinatorial chemistry approaches. Combinatorial synthetic methods are unlikely to produce molecules of the complexity of rapamycin and Taxolä. The process of drug development is often a risky, costly endeavor, and according to the Merk company, “for every 1000 substances that are evaluated in biological assays, 20 are selected for animal testing. Of these 20, 10 will be evaluated in humans and only one will be approved by the Food and Drug Administration (FDA) in the United States for sales as a drug” (Ciba, 42). This process requires 12 years and is estimated to cost $231 million. In 1985, 119 secondary metabolites isolated from higher plants were identified in use world-wide, and 75% of these plants had same or related use as the plants from which they were discovered. Many of these drugs are “prototype drugs” that have been used for decades and are still effective, including: codeine, atropine, scopolamine, morphine, tubocurarine, reserpine, and pilocarpine. Ciba proposes that plants can be selected on the basis of numerous criteria, including studying shaman practices, databasing latin names and use of natural products, random collection of plants, chemotaxonomy studies (ie, lactone, vs. alkaloid-producing plants for different ailments), and combining plant extract studies as well as ethnomedical claims of activity.
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The Value of The Rainforests
The Fate of the RainforestMedicines Discovered from rainforest Plants