Anticancer drugs taxol

Borman, S. 1991. Scientists Mobilize to Increase Supply of Anticancer Drug Taxol. 

Combined species substitution and chemicai synthesis—the best exampie of this is the production of analogues of the anticancer drug taxol which is now made by using a species related to that which makes taxol (see Chapter 7). This related species make no NPs with useful anticancer properties, but one of its NPs can be converted to the useful analogue of taxol by chemists. 

The second chapter addresses new facets of the medicinal chemistry of the important anticancer drug Taxol (paclitaxel). Ojima and coworkers explore, in particular, the structure-activity relationship associated with the 3-phenylisoserine side chain, synthetically exploiting their P-Lactam Synthon Method . Their research has led to, among other things, a series of noteworthy second-generation taxoid anticancer agents. 

One of the synthetic routes for the anticancer drug Taxol, which has twelve stereo centers, involves a homogeneous C-C coupling reaction. The industrial production of a protease inhibitor that has stereospecific arrangements of amino and hydroxyl groups on two adjacent carbon atoms also involves homogeneous catalysis. From Table 1.1 identify the possible reaction types that are used in these two syntheses. 

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.

The anticancer drug taxol is produced by endophytes from Taxus brevifolia (Stierle et al., 1993). An isolated occurrence of the taxan alkaloids has been reported from Corylus avellana (Betulaceae), which is not associated with an endophyte (although the pathway genes might have been imported by an endophyte at an earlier stage) (Ottaggio et al., 2008). Podophyllotoxin is produced by endophytes of Podophyllum peltatum (Eyberger et al, 2006). 

The example of the anticancer drug Taxol, introduced by Bristol-Myers Squibb in 1993, demonstrates how to overcome the obstacles affecting the development... 

A number of books deal with poisonous plants, as cited previously in the section Poisons in Nature, Chapter 1. Among the noted species of current interest are Western yew trees of the family Taxaceae, which contain the poisonous alkaloid taxine (Hardin and Arena, 1974, p. 42). The anticancer drug Taxol, for instance, is derived from the yew of the Pacific coast (Taxus brevifolia). 

The antimitotic mechanism of taxol differs from the antimicrotubule agents such as colchicine and the vinca alkaloids discussed earlier. Rather than causing disassembly of the microtubules, taxol actually enhances tubulin polymerization. This upsets the normal dynamic equilibrium between soluble tubules, which are dimers, and the microtubule polymers. The stabilization of the latter inhibits mitosis in the latter part of Phase G2 and M. Although sharing much of the toxicology of many of the anticancer drugs, taxol promises to be an important addition to the cancer armamentarium. 

In one study (60) aimed at identifying and quantifying, from various plant extracts, new compounds related to the anticancer drug taxol, polyclonal antibodies were raised using 2-succinyl taxol-bovine serum albumin (Fig. 9) as the immunogen. These antibodies were then used to develop an enzyme-linked immunosorbent assay (ELISA) that was specific for the taxol family. This taxol ELISA assay was used to monitor solvent partitions and chromatographic fractions of extracts of Taxus brevifolia from different sources. Five different ELISA-positive taxoids were isolated, one of which was previously unreported. 

The anticancer drugs Taxol and Taxotere feature a (2R, 35)-V-benzoyl phenylisoserine as side chain. A number of stereoselective syntheses of this moiety have been reported. Among them, the preparation based on the catalytic asymmetric aminohydroxylation protocol recently developed by Sharpless and reported in Fig. 26 seems particularly attractive [77]. 

Figure 3.1 A promising anticancer drug, taxol, is isolated from the bark of the Pacific yew tree. Though taxol is a complex compound, what does its name suggest about its structure ...

Cyclic ethers are components of many natural products as well as synthetic compounds. A simple one is erythritol anhydride (63), which contains the epoxide unit and is used to prevent microbial spoilage. The important anticancer drug taxol (64) contains an oxetane unit. The tetrahydrofiiran unit is a component of the important carbohydrate ribose (65), which is the sugar portion of RNA (see Chapter 28). A tetrahydrofuran unit is found in isosorbide dinitrate (Isordil , 66), which is a vasodilator used in the prevention and treatment of angina. The tetrahydropyran unit is found in common sugars such as glucose (67) and in desosamine (68), which is the sugar component of many macrolide antibiotics. Both the tetrahydrofuran and tetrahydropyran rmits are found in the antibiotic Lasalocid (69). 

Anticancer drug Taxol entophytic fungi diversity fermentation biosynthesis pathway... 

Han KH, Fleming P, Walker K, Loper M, Chilton WS, Mocek U, Gordon MP, Floss HG (1994) Genetic transformation of mature Taxus an approach to genetically control the in vitro production of the anticancer drug, taxol. Plant Sci 95 187-196... 

Kumaran RS, Hur BK (2009) Screening of species of the endophytic fungus Phomopsis for the production of the anticancer drug taxol. Biotechnol Appl Biochem 54 21-30. doi 10.1042/BA20080110... 

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