Taxol chemical structures

Camptothecin was discovered as an active anticancer drug isolated from the bark of Camptotheca acuminata. The anticancer activity of camptothecin was discovered in the 1960s by the National Cancer Institute (NCI) as part of a systematic effort to screen for novel anticancer agents derived from natural products. Monroe Wall and Mansuhk Wani identified the chemical structure of camptothecin. They also identified the chemical structure of taxol, again under the auspices of the NCI. Susan Hoiwitz was contracted by the NCI to elucidate the anticancer mechanisms of camptothecin. She found in the early 1970s that camptothecin induced DNA breaks and attested DNA and RNA synthesis. However, it is approximately 12 years later, only after DNA topo-isomerase I (Topi) had been identified in human cells, that Leroy Liu and his coworkers found that Topi was the cellular target of camptothecin [reviewed in [1]. 

FIGURE 62.1 Chemical structures of paclitaxel (taxol) and its more potent analog, docetaxel (taxotere). 

There is a high level of expression of P-gp in the epithelial cells of the small intestine. Compounds that have been found to be substrates exhibit a wide range of chemical structures. However, they tend to be lipophilic and, for some, cationic, such as anthracyclines, vinca alkaloids, cyclosporin, etoposide, and celiprolol. It has been shown that taxol, an anti-microtubule anticancer drag, was not absorbed after oral administration in pre-clinical trials. This can probably be attributed to P-gp, since the flux from the... 

Actually, the chemical structure and purity of both is identical. However, being able to make taxol synthetically is a real advantage drug companies may be able to produce it more cheaply, and they can work on modifying its structure to make it more... 

Fig. 1 Chemical structures of Colchicine (1), Vinblastine (2), Vincristine (2a) and Taxol...

Figure 8.2 Conjugation of paclitaxel to PEG enhances solubility in water. Chemical structures of paclitaxel (Taxol , (a)) and Taxol 2 -PEG ester (b).

Figure 16.1 Chemical structures of some mitotic inhibitors. Microtubule modulators taxol (1) and vinblastine (2), Eg5 inhibitor ispinesib (3), CENP-E inhibitor GSK923295 (4), PIkl inhibitor GSK 461364 (5), Aurora A inhibitor MLN8054 (6), and Mpsi inhibitor reversine (7).

Scheme 15 Chemical structure of first and second generation disassembled dendrons with a nitro trigger and taxol reporters...

Besides their essential roles in nature, isoprenoids are of commercial importance in industry. Some isoprenoids have been used as flavors, fragrances, spices, and food additives, while many are used as pharmaceuticals to treat an array of human diseases, such as cancer (Taxol), malaria (artemisinin), and HIV (coumarins). In contrast to the huge market demand, isoprenoids are present only in low abundance in their host organisms. Thus, isolation of the required isoprenoids consumes a large quantity of natural resources. Furthermore, owing to their structural complexity, total chemical synthesis is often not commercially feasible. For these reasons, metabolic engineering may provide an alternative to produce these valuable isoprenoids [88,89]. 

Figure 12.4 The molecular structure of a taxane [114]. Taxotere is the semi-synthetic congener of Taxol. (Reproduced by permission from Macmillan Publishers Ltd Susan C. Roberts. Production and engineering of terpenoids in plant cell culture. Nature Chemical Biology 3 (7) 387-395. London Nature Publishing Group. 2007 Macmillan)...

Wani, M.C., Taylor, H.L., Wall, M.E. etal. (1971) Plant antitumor agents. VI. Isolation and structure of Taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. Journal of the American Chemical Society, 93, 2325-2327. 

Fig. 30 Taxoid site on (3-tubulin and predicted peloruside site on a-tubulin. a Surface representation (view from the inner side of the microtubule) of a tubulin dimer with FIX (red) bound to P-tubulin (green) and peloruside A (orange) bound to the predicted site in a-tubulin (blue), b View of the peloruside binding site. Hydrogen bonds are represented as yellow dashed lines, and the residues involved in these bonds are labeled. Some secondary structure elements are also labeled, c View of the taxol binding site. Some secondary structure elements are labeled. In panels b and c, H7 is colored in orange, and the N-terminal and intermediate domains are colored in green and blue, respectively. (Reprinted with permission from [17]. Copyright 2006 American Chemical Society)...

Figure 5.29. PAMAM dendrimer multifunctional conjugates for cancer treatment. The FA group is a folic acid cancer cell target, and FITC is fluorescein isothiocyanate, used as an imaging agent. Also shown (bottom) is the molecular structure for the anticancer drug, taxol, denoting the -OH group that covalently attaches to the dendrimer. Reproduced with permission from Majoros, I. J. Myc, A. Thomas, T Mehta, C. Baker, J. R. Biomacromolecules, 2006, 7, 572. Copyright 2006 American Chemical Society.

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