Pacific yew tree

A new antitumor drug, taxol, has been isolated from the bark of Taxus brevifolia, the Pacific yew tree. Like vinblastine and colchicine, taxol inhibits cell replication by acting on microtubules. Unlike these other antimitotic drugs, however, taxol stimulates microtubule polymerization and stabilizes microtubules. 

F.14 Paclitaxel, which is extracted from the Pacific yew tree Taxus brevifolia, has antitumor activity for ovarian and breast cancer. It is sold under the trade name Taxol. On analysis, its mass percentage composition is 66.11% C, 6.02% H, and 1.64% N, with the balance being oxygen. What is the empirical formula of paclitaxel ... 

Another drug is taxol, which is extracted from the bark of the Pacific yew tree, Taxus brevijolia. Unlike colchicine and the vinca alkaloids, taxol binds tightly to microtubules and stabilizes them against depolymerization by Ca. It also enhances the rate and yield of microtubule assembly, thereby decreasing the amount of soluble tubulin in the cytosol pool. Again, the overall effect of taxol is to arrest dividing cells in mitosis. Taxol is used in cancer chemotherapy. 

The answer is c. (Hardman, pp 1260—1262.) Paclitaxel is a large structural molecule that contains a 15 membered taxane ring system. This anti cancer agent is an alkaloid derived from the bark of the Pacific yew tree. Its chemotherapeutic action is related to the microtubules in the cell. Paclitaxel promotes microtubule assembly from dimers and causes microtubule stabilization by preventing depolymerization. As a consequence of these actions, the microtubules form disorganized bundles, which decreases... 

Since the discovery of the anticancer potential of Taxol , a complex compound isolated from the bark extract of the Pacific yew tree, more than 20 years ago, there has been an increasing demand for the clinical application of this compound. First, the promising results of the 1991 clinical trials in breast cancer patients were announced, and soon after Bristol-Myers-Squibb trade-marked the name Taxol and used it as an anticancer drug. At that point, the only source of the drug was the bark of the endangered yew tree. Fortunately, it was soon discovered that a precursor of Taxol could be obtained from an extract of the tree needles instead of the bark. 

Early production of 1 kg of paditaxel required extraction from about 13,000kg of the Pacific yew tree bark. This process was refined, and pacli-taxel is now produced by a semisynthetic route. The starting material, 10-deacetyl baccatin 111 (10-DAB), is obtained from the needles of Taxus baccata (European yew) or T. wallichiana (Himalayan yew). The yield is around 1000 kg of needles to produce 1kg of 10-DAB. 

Wancer is one of the leading causes of death in Canada. It is a disease in which cells mutate and grow at uncontrolled rates, disrupting the body s normal functions. TAXOL , shown at the bottom of the page, is an organic compound that is found in the bark of the Pacific yew tree. After many tests and reviews, TAXOL was approved for use in treating ovarian cancer. 

The needles and twigs of the European yew contain 10-deacetylbaccatin III, shown at the bottom of the page. A few reaction steps can transform 10-deacetylbaccatin III into TAXOL . Instead of destroying an entire Pacific yew tree for a single treatment of TAXOL , scientists can now use the needles from a European yew. The parent tree is not harmed. 

Taxol i is a naturally occurring substance isolated from the Pacific yew tree Taxus brevifolia), which has been approved for clinical treatment of cancer patients. Taxol enhances polymerization of tubuhn and the consequent formation of stable microtubules, inhibiting cellular mitosis. 

Taxol is an anticancer drug obtained from the Pacific yew tree (Taxuxbrevifolia). (Mix/ Phanie/Photo Researchers, Inc.)... 

Hopes for using paciltaxel in the treatment of cancer were dampened, however, by the fact that the Pacific 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... 

Formidable chemical obstacles stood in the way of clinical development of these agents derived from natural products, notably in formulation of very poorly soluble compounds for intravenous infusion and in manufacture of bulk drug. For a time, production of Taxol from the bark of the Pacific Yew tree aroused public controversy, which became a story of nature and politics in pursuit of an anti-cancer drug [22]. 

Taxol was the most triumphant new anticancer drug developed in the last few decades. It resulted from a drive to screen thousands of synthesized compounds and plant extracts, financed by the National Cancer Institute (Georg et al. 1994, Suffness 1995, Goodman and Walsh 2001). Taxol is extracted from the bark of the Pacific yew tree, or Taxus brevifoli, found in the Pacific Northwest, and has been proven effective against intractable breast and ovarian cancers. It is now produced by semi-synthetic methods from the needles of the common ornamental tree English Yew, or Taxus baccata. We will discuss taxol in greater detail in Chapter 2. 

There are several books on the history of the development of taxol, which is one of the most remarkable stories in product development. In fact, it inspired the 1992 motion picture Medicine Man, starring Sean Connery as a research botanist looking for a cancer cure in the Brazilian rain forest. For a time, it became a moral drama pitting the needs of patients of intractable ovarian and breast cancer against the passions of environmentalists to preserve an obscure Pacific yew tree. Suffness and Wall are two of the principals in this story, and they wrote (1995) It [Taxol] is not an obvious winner till the very end, and there were a number of times till the very end when it seemed highly likely that it would not be put into development at all, or that once it had been accepted, it would be dropped. More than 30 years passed between the discovery of taxol, with its potential as an anticancer drug, and its approval by the Food and Drug Administration (FDA) for clinical use. 

Paclitaxel was first manufactured by extracting the active drug from the bark of the Pacific yew tree, but that approach was imac-ceptable, both for the manufacturer, Bristol-Myers Squibb, and for... 

The diterpenoid taxol (Figure 1.12) was first isolated from the pacific yew tree (Taxus brevifolia) in the late 1960s. Its complete structure was elucidated by 1971. Difficulties associated with the subsequent development of taxol as a useful drug mirror those encountered during the development of many plant-derived metabolites as drug products. Its low solubility made taxol difficult to formulate into a stable product, and its low natural abundance required large-scale extraction from its native source. 

Paclitaxel (Taxol) is a highly complex, organic compound isolated from the bark of the Pacific yew tree. It binds to tubulin dimers and microtubulin filaments, promoting the assembly of filaments and preventing their depolymerization. This increase in the stability of microfilaments results in disruption of mitosis and cytotoxicity and disrupts other normal microtubular functions, such as axonal transport in nerve fibers. 

Evidence of the importance of as yet unanticipated information on naturally occurring agents, the U.S. Department of Agriculture in late 1991 granted Bristol-Myers Squibb Company the authority to harvest the bark of Pacific yew trees in federal forests for the chemical taxol, a potential anticancer drug. Soon after other natural and synthetic precursors were developed so that the natural sources would not be depleted. 

Figure 7.2 Pacific yew tree Taxus brevifolia) tree and bark detail.

Taxol has had a most unusual clinical development history. As with many natural products that have been discovered to provide therapeutic benefit to humans, it was the extract of a plant that provided the first hint of the oncological potential of this product. Natural product chemists typically subject purified plant extracts to screening for therapeuhc achvity. In 1963, an extract of the bark of the Pacific yew tree (Taxus brevifolia (Figure 7.2) showed anti-tumor activity. This early work was done by Monroe Wall and Monsukh Wani of the Research Triangle Institute (RTI) under the auspices of the National Cancer Institute (NCI) [3]. 

From Extraction of Taxol from Pacific Yew Tree Bark to Semi-SYnthetic Taxol 1147... 

With the successful development and commercial manufacture of semi-synthetic Taxol , tile destruction of the Pacific yew tree forests was halted. However, this successful move away from an essentially non-renewable source (extraction of the Pacific yew tree bark) to a renewable source (harvested European yew tree leaves and twigs to obtain 10-DAB, followed by syntliettc transformation to Taxol ) still presented significant environmental challenges. The use of 13 different solvents. 

Paclitaxel (Taxot ) Paclitaxel (85) is one of the most promising compounds against several types of cancer, and a number of elegant total syntheses have been reported in recent years [99], It is produced by the slow growing pacific yew tree, and therefore its availability is limited. By partial synthesis, it is best prepared from 10-deacetylbaccatin III, a derivative lacking the C-10 acetoxy fragment as well as the C-l 3 side chain. Therefore, many efforts have been focused on... 

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