isolated a substance,which they called compound 17,responsible for this antitumor activity.Compound 17 was later renamed paciltaxel. Hopes for using paciltaxel in the treatment of cancer were dampened,however. by the fact that the Pacifi c yew tree is a slow-growing,threatened tree.Its harvest for the collection of paciltaxel from its bark would almost certainly have led to the tree's extinction.Instead,researchers turned to the obvious alternative,characterization of the chemical structure of paciltaxel and its chemical synthesis.That task was a challenge,however,because of the complex structure of the paciltaxel molecule. After more than a decade of research,however,the task was accomplished: Researchers achieved a successful method for the synthesis of the compound in the laboratory.In1992,the FDA approved paciltaxel for use against cancers that had failed to respond to other treatments.By this time,the compound was being made and marketed by Bristol-Myers Squibb Company under the trade name of Taxol.Over the next decade,the FDA continued to expand the diseases for which Taxol could be used,including breast,ovarian,and lung cancer and Kaposi's sarcoma related to HIV infection. Another success story involving the development of anticancer agents is that of a drug known as camptothecin.The same researcher who had begun study of pacitaxel, Dr.M.E.Wall,first studied the natural product from which this drug was originally obtained,a tree native to China called Camptotheca acuminata.in the late 1950s Although initial studies of its effects on tumors were encouraging.later tests were ambiguous,and interest in the anticancer and antiviral properties.In 2007,a number of products are at various stages of testing,including combretastatin A4,isolated from the South African medicinal tree.Combrem cffrump:homoharringtonine,from the tree Cephalotaxus harringtonia found in mainland China;ingenol 3-0-angelate, originally obtained from a common English and Australian tree Euphorbia peplus: and phenoxodiol,a synthetic analog of daidzein,obtained from soybean.This field of research obviously holds great promise for the development of new antiviral and anticancer drugs
isolated a substance, which they called compound 17, responsible for this antitumor activity. Compound 17 was later renamed paciltaxel. Hopes for using paciltaxel in the treatment of cancer were dampened, however, by the fact that the Pacifi c yew tree is a slow-growing, threatened tree. Its harvest for the collection of paciltaxel from its bark would almost certainly have led to the tree’s extinction. Instead, researchers turned to the obvious alternative, characterization of the chemical structure of paciltaxel and its chemical synthesis. That task was a challenge, however, because of the complex structure of the paciltaxel molecule. After more than a decade of research, however, the task was accomplished: Researchers achieved a successful method for the synthesis of the compound in the laboratory. In 1992, the FDA approved paciltaxel for use against cancers that had failed to respond to other treatments. By this time, the compound was being made and marketed by Bristol-Myers Squibb Company under the trade name of Taxol®. Over the next decade, the FDA continued to expand the diseases for which Taxol® could be used, including breast, ovarian, and lung cancer and Kaposi’s sarcoma related to HIV infection. Another success story involving the development of anticancer agents is that of a drug known as camptothecin. The same researcher who had begun study of pacitaxel, Dr. M. E. Wall, first studied the natural product from which this drug was originally obtained, a tree native to China called Camptotheca acuminata, in the late 1950s. Although initial studies of its effects on tumors were encouraging, later tests were ambiguous, and interest in the anticancer and antiviral properties. In 2007, a number of products are at various stages of testing, including combretastatin A4, isolated from the South African medicinal tree, Combretum caffrump; homoharringtonine, from the tree Cephalotaxus harringtonia found in mainland China; ingenol 3-O-angelate, originally obtained from a common English and Australian tree Euphorbia peplus; and phenoxodiol, a synthetic analog of daidzein, obtained from soybean. This field of research obviously holds great promise for the development of new antiviral and anticancer drugs
The Search for New Natural Product Drugs Until the 1950s,the world approached the use of drugs to treat disease in either of two ways.Generally speaking. people living in developing nations relied primarily on natural products,especially herbs,to treat disease.while those living in developed nations put their faith in modern scientifi c medicine,usually synthetically produced chemical compounds,for the same purposes.The line between these two practices began to break down when scientific researchers started to search for the chemical compounds in natural products that are biologically active,research characterized by the work of Wall and Wani described in the previous section.In fact,the accomplishments of Wall and Wani prompted the National Cancer Institute(NCI)and the U.S.Department of Agriculture (USDA)to initiate a formal program for the collection and screening of plants with potential anticancer activity. Between 1960 and 1982.that program was responsible for the collection of more than 35,000 plant samples,from which 14,000 unique extracts were obtained. In addition,field-workers collected 18000 extracts from marine organisms.NCI and USDA terminated the program in 1982 because of limited success:Only seven plantderived anticancer drugs had been developed as a result of the program,four resulting from Wall and Wani's 1950s research.NCI reactivated the program in1986 as its Natural Products Branch(NPB).a division that remains in existence today.In 1988,the institute also began to search for drugs that might be effective against AIDS. Since its reactivation,NPB has screened more than 40,000 plant extracts.One of those,Taxo has been approved for use,and five others with potential use against AIDS have been isolated.Three of those are now in preclinical trials. Researchers have adopted three approaches in their search for new drugs among natural products.First,they sometimes use a"broadcast"approach in which they simply collect and study all the plants or marine organisms within a certain geographical area.The advantage of this approach is that large numbers of samples can be collected in a relatively short time.The disadvantage is that there is seldom any particular reason for expecting to find a useful compound in any given area. A second approach is to focus on plants or marine organisms that are known to
The Search for New Natural Product Drugs Until the 1950s, the world approached the use of drugs to treat disease in either of two ways. Generally speaking, people living in developing nations relied primarily on natural products, especially herbs, to treat disease, while those living in developed nations put their faith in modern scientifi c medicine, usually synthetically produced chemical compounds, for the same purposes. The line between these two practices began to break down when scientific researchers started to search for the chemical compounds in natural products that are biologically active, research characterized by the work of Wall and Wani described in the previous section. In fact, the accomplishments of Wall and Wani prompted the National Cancer Institute (NCI) and the U.S. Department of Agriculture (USDA) to initiate a formal program for the collection and screening of plants with potential anticancer activity. Between 1960 and 1982, that program was responsible for the collection of more than 35,000 plant samples, from which 114,000 unique extracts were obtained. In addition, field-workers collected 18,000 extracts from marine organisms. NCI and USDA terminated the program in 1982 because of limited success: Only seven plantderived anticancer drugs had been developed as a result of the program, four resulting from Wall and Wani’s 1950s research. NCI reactivated the program in 1986 as its Natural Products Branch (NPB), a division that remains in existence today. In 1988, the institute also began to search for drugs that might be effective against AIDS. Since its reactivation, NPB has screened more than 40,000 plant extracts. One of those, Taxol®, has been approved for use, and five others with potential use against AIDS have been isolated. Three of those are now in preclinical trials. Researchers have adopted three approaches in their search for new drugs among natural products. First, they sometimes use a “broadcast” approach in which they simply collect and study all the plants or marine organisms within a certain geographical area. The advantage of this approach is that large numbers of samples can be collected in a relatively short time. The disadvantage is that there is seldom any particular reason for expecting to find a useful compound in any given area. A second approach is to focus on plants or marine organisms that are known to
contain biologically active compounds.The hope is that such plants or marine organisms may yield new and different chemicals that may also be effective against certain types of disease Finally,researchers may use an ethnobotanical approach.that is,one that focuses on medicinal plants that have traditionally been used in various cultures.The assumption underlying this approach is that plants on which people have relied for medicines in the past may very well contain biologically active chemicals that can be either isolated,purified,and used as drugs or used as models from which biologically active analogs can be produced. Once a plant or marine organism sample has been collected,it is labeled,stored. and then treated chemically to remove its primary components.Next,these components(extracts)are tested to determine whether or not they show any biological activity.The tests (bioassays)are used to identify any toxicity or other effect an extract may have against target cells(such as cancer cells),organisms (such as parasites),or chemicals(such as allergens).Extracts that seem to be effective against any one of these targets are then analyzed in more detail to fi nd out what chemical(s) they contain that produce the biological activity.When and if such compounds are identified,they are then subjected to the long and detailed series of tests for safety and efficacy that all new drugs undergo. Cinical rial Led deveiopment Ls时omion Figure 1.Drug discovery process from plants
contain biologically active compounds. The hope is that such plants or marine organisms may yield new and different chemicals that may also be effective against certain types of disease. Finally, researchers may use an ethnobotanical approach, that is, one that focuses on medicinal plants that have traditionally been used in various cultures. The assumption underlying this approach is that plants on which people have relied for medicines in the past may very well contain biologically active chemicals that can be either isolated, purified, and used as drugs or used as models from which biologically active analogs can be produced. Once a plant or marine organism sample has been collected, it is labeled, stored, and then treated chemically to remove its primary components. Next, these components (extracts) are tested to determine whether or not they show any biological activity. The tests (bioassays) are used to identify any toxicity or other effect an extract may have against target cells (such as cancer cells), organisms (such as parasites), or chemicals (such as allergens). Extracts that seem to be effective against any one of these targets are then analyzed in more detail to fi nd out what chemical(s) they contain that produce the biological activity. When and if such compounds are identified, they are then subjected to the long and detailed series of tests for safety and efficacy that all new drugs undergo. Figure 1. Drug discovery process from plants
Creating New Medicines is a High Risk Journey 15 Medicine 10 w Natural Product Research and Biodiversity Over the past few decades,the use of natural products as drugs and dietary supplements has raised an increasingly important question:What impact does it have on biodiversity?The widespread popularity of some natural products has resulted in their rapid destruction in the environment.One of the best-documented examples of this pattern is the decimation of wild echinacea resources throughout the United States Sales of the plant in 2002 amounted to more than $32 million,and manufacturers are eager to obtain as much as they can from American sources.As a result,the plant is rapidly being depleted from its natural habitat,which ranges across large parts of the Midwest. The popularity of ginseng has already led to its extinction in some parts of the world (such as South Korea)and to its classifi cation as an endangered species in other parts(such as China)due to overharvesting. Today,more than 65 tons of the root are harvested in the United States each year,most of it going to the Far East.At this rate,the plant faces possible extinction in this country also.Goldenseal is yet another threatened herb in the United States and
Natural Product Research and Biodiversity Over the past few decades, the use of natural products as drugs and dietary supplements has raised an increasingly important question: What impact does it have on biodiversity? The widespread popularity of some natural products has resulted in their rapid destruction in the environment. One of the best-documented examples of this pattern is the decimation of wild echinacea resources throughout the United States. Sales of the plant in 2002 amounted to more than $32 million, and manufacturers are eager to obtain as much as they can from American sources. As a result, the plant is rapidly being depleted from its natural habitat, which ranges across large parts of the Midwest. The popularity of ginseng has already led to its extinction in some parts of the world (such as South Korea) and to its classifi cation as an endangered species in other parts (such as China) due to overharvesting. Today, more than 65 tons of the root are harvested in the United States each year, most of it going to the Far East. At this rate, the plant faces possible extinction in this country also. Goldenseal is yet another threatened herb in the United States and
other parts of the world.It currently sells for about $100 a pound,making it highly popular for individual,independent workers who tear it out of its natural habitat.In 2003,the Convention on International Trade in Endangered Species proposed listing it as an endangered species. Such losses are potentially serious problems for drug research.Maintaining biodiversity is an essential component of future research efforts to identify possible drugs in the world's plant and marine resources.Scientists have no idea how many species there are in the world,but reasonable estimates place the numbers at about 250,000 plant species and up to I million marine species.So far,no more than about 10 percent of all plants and 1 percent of all marine organisms have been studied for possible use as drugs Given these circumstances,it is possible that countless numbers of new natural products with potential for use as drugs are still waiting to be discovered.As more and more plants and animals are destroyed each year by deforestation,development. and other forces,those natural products are being to lost for possible future use. Natural Products as Dietary Supplements Ask the average person on the street about"natural products,"and he or she is likely to mention the kinds of products found on the shelves of grocery stores and stores that specialize in "organic"and "natural"foods.Those items are overwhelmingly plant products,and they range from aconitum napellus(monkshood) alfalfa,allium cepa,aloe vera,angelica,and anise seed to witch hazel,yarrow,yellow dock,yohimbe bark,and yucca.Healers have used many of these products for centuries,and they remain widely popular with people in countries around the world today,both developed and developing. In many cultures, Echinacea Stimulates immune system Ginkgo (Ginkgo biloba)Improves concentration and memory;protects against Alzheimer's disease
other parts of the world. It currently sells for about $100 a pound, making it highly popular for individual, independent workers who tear it out of its natural habitat. In 2003, the Convention on International Trade in Endangered Species proposed listing it as an endangered species. Such losses are potentially serious problems for drug research. Maintaining biodiversity is an essential component of future research efforts to identify possible drugs in the world’s plant and marine resources. Scientists have no idea how many species there are in the world, but reasonable estimates place the numbers at about 250,000 plant species and up to 1 million marine species. So far, no more than about 10 percent of all plants and 1 percent of all marine organisms have been studied for possible use as drugs. Given these circumstances, it is possible that countless numbers of new natural products with potential for use as drugs are still waiting to be discovered. As more and more plants and animals are destroyed each year by deforestation, development, and other forces, those natural products are being to lost for possible future use. Natural Products as Dietary Supplements Ask the average person on the street about “natural products,” and he or she is likely to mention the kinds of products found on the shelves of grocery stores and stores that specialize in “organic” and “natural” foods. Those items are overwhelmingly plant products, and they range from aconitum napellus (monkshood), alfalfa, allium cepa, aloe vera, angelica, and anise seed to witch hazel, yarrow, yellow dock, yohimbe bark, and yucca. Healers have used many of these products for centuries, and they remain widely popular with people in countries around the world today, both developed and developing. In many cultures, Echinacea Stimulates immune system Ginkgo (Ginkgo biloba) Improves concentration and memory; protects against Alzheimer’s disease