Anticancer drugs taxans

As will be mentioned further in this chapter, the discovery of the anticancer drug, paclitaxel (21), was soon followed by sourcing issues due to the low yield of this compound in the source plant, Taxus brevifolia Nutt. This led to the semisynthesis of paclitaxel (21), from a precursor molecule, 10-deacetylbaccatin III, readily available from the leaves of Taxus baccata L., a renewable source with high yields of this compound.Docetaxel (37) is a second taxane class anticancer drug and is a semisynthetic derivative of paclitaxel (21). ... 

The taxanes are a group of polycyclic diterpenes produced by various species of trees (such as yew) and are most commonly known as the potent anticancer drug paclitaxel (Taxol). The extraction process is costly. 

Holton, R. A. Chai, K. B. Nadizadeh, H. "Preparation of Butenyl-substituted Taxanes as Anticancer Drugs, U.S. Patent, 1994,5,284,864 Chem. Abstr. 1994,121,301103v. 

MDR is one major reason for the failure of chemotherapy. Overexpression of P-glycoprotein (P-gP), which results in massive transport of anticancer drugs and other hydrophobic substrates out of cells, is the best known contributing factor to MDR. Also, other factors attributing to the failure of taxane anticancer drugs, such as inherently insensitive isotypes of tubulin and amino acid mutations in mbulin, will also be discussed in this section. 

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 anticancer drugs delivered by liposomes include many small molecule drugs such as DOX, daunoru-bicin, platinates, taxanes, camptothecin, etc. The most successful development is DOX-encapsulated pegylated liposomes, with a trade name of Doxil in the U.S. market or Cylax in the European market. Doxil has shown significant clinical advantages over free DOX and conventional DOX liposomes.f Enhanced tumor accumulation of Doxil has been demonstrated in numerous preclinical studies over a variety of tumor models. Similar effects were also observed in clinical uses. 

Taxus (yew) trees contain alkaloids called taxanes that have anticancer activity and are the basis of the semisynthetic anticancer drugs paclitaxel and docetaxel (see separate monographs), which are based on taxol, from Taxus brevifolia. 

A genetic profile on the basis of SNPs would be more than useful for Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) risk stratification, prior to start treatment. CIPN is a potentially severe and long-lasting side effect of commonly employed anticancer drugs platinum compounds, taxanes, proteasome inhibitors, vinca alkaloids, and epothilones they are used every day to treat... 

Heaton DM, Bartle KD, Rayner CM, Clifford AA. Application of supercritical fluid extraction and supercritical fluid chromatography to the production of taxanes as anticancer drugs. J High Resolut Chromatogr 1993 16 666-670. 

Taxanes (tetracyclic terpenoids with oxetane fragment), anticancer drugs with unique mechanism of action 00CLY226. 

FIGURE 16.9 Anticancer drug paclitaxel 33. (A) Enzymatic cleavage of the C-13 side chain from taxanes. (B) Enzymatic cleavage of the C-10 acetate from taxanes. (C) Enzymatic cleavage of the C-7 xylosyl groups from taxanes. 

Beck WT, Cass CE, Houghton PJ. Microtubule-targeting anticancer drugs derived from plants and microbes vinca alkaloids, taxanes, and epothiolones. In Bast RC Jr, Kufe DW, Pollock RE, Weichselbaum RR, Holland JF, Frei E III, eds. Holland-Frei Cancer Medicine. 5th Ed. Hamilton, Ontario BC Decker, 2000 680-698. 

Lin S, Ojima I (2000) Recent Strategies in the Development of Taxane Anticancer Drugs Exp Opin Ther Patents 10 1... 

As mentioned before, the market demand of the anticancer drug, paclitaxel (15, Taxol ) was threatened initially by an unsustainable natural supply, which relied mainly on extracting this compound from the bark of the slow-growing Pacific yew tree, from which it is produced only in a very low yield [57]. Although the total synthesis of paclitaxel has been described, this is still inefficient when considered the extensive market need [58-60]. 10-Deacetylbaccatin El (22), which is available with a relatively high yield from the leaves of other renewable yew species, such as Taxus baccata L., was introduced as a semi-synthetic precursor compound of paclitaxel by the major pharmaceutical manufacturer, Bristol-Myers Squibb (B-MS) [61]. Docetaxel (23), a related taxane anticancer drug can also prepared from 10-deacetylbaccatin El (22) [62]. 

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