Anticancer agent taxol used

Historically, plant-based natural products have been a source of useful drugs. The analgesic opiates come from the poppy plant. Digitalis for congestive heart failure was first isolated from the foxglove plant. Various antibiotics (penicillin) and anticancer agents (taxol) are derived from natural product sources. There are numerous other examples. 

The anticancer agent, taxol, is now obtained from a number of Taxus species but invariably occurs with with sizeable amounts of the congener, cephalomannlne. These complex diterpenes differ only in the nature of the amide carboxylic acid attached to the amine of the phenylisoserine side chain. In the case of taxol this is a benzoic acid moiety, whereas in cephalomannlne it is a tiglic acid group. These two impart very little selective polarity to the two natural products, and separation of them is notoriously difficult. Almost baseline separation of a small sample (6.1 mg) was achieved, however, by Chu and his coworkers (6), using a system of hexane-ethyl acetate-methanol-etha-nol-water (10 14 10 2 13) with the aqueous phase mobile. In this system, taxol had a partition coefficient of 1.8 and cephalomannlne of 1.42. 

The discovery of the novel diterpenoid anticancer agent taxol in 1971 by Monroe Wall and his collaborators ranks in retrospect as one of the most significant discoveries ever made in the field of naturally occurring anticancer agents. Although extensive researches have been done on natural anticancer agents, only a handful of plant-derived natural products have been found to show clinically useful activity, and taxol is clearly a member of this group. 

In recent years, however, some of the greatest emphasis has been placed on the search for anticancer and antiviral agents derived from natural products. Success in that area has not heen as great as that achieved in other helds. Since 1960, only seven plant-derived drugs have heen approved by the FDA for use as anticancer agents. Four of those drugs, vinblastine, vincristine, etoposide, and teniposide, were discovered in the 1950s. The last three—Taxol , topotecan, and irinotecan—were discovered and approved much more recently. 

In the anticancer area, the use of natural products as direct agents or as novel lead compounds for the generation of synthetic or semisynthetic analogs has proved remarkably productive, and a recent survey showed that 62% of new anticancer agents over the last 10 years have been natural products or agents based on natural product models.7 Examples of clinically important plant-derived natural products are the vinca alkaloids vinblastine (4) and vincristine (5), the podophyllotoxin analogs etoposide (6) and teniposide (7), the diterpenoid paclitaxel (Taxol ) (8), and the camptothedn-derivative topotecan (9). 

In this chapter, we describe an account of our research on the chemistry and biology of paclitaxel and taxoid anticancer agents (taxoid = taxol-like compound). The topics covered in this chapter include (i) the development of a practical and efficient method for the semisynthesis of paclitaxel and docetaxel using chiral 3-hydroxy-P-lactams as synthetic intermediates, (ii) structure-activity relationship (SAR) studies of various taxoids that led to the discovery of the extremely potent second-generation taxoids, and (iii) biological and conformational studies with the use of fluorine-containing taxoids as probes. ... 

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.

This chapter gives an account of our research on the use of fluorine, exploiting the unique nature of this element, in the medicinal chemistry and chemical biology of taxoid anticancer agents (i.e., Taxol-like compounds). 

In further confirmation, there are antibiotics prominently listed in Appendices E and E of Hoffman (1999) as inhibitors for enzymes involved in DNA and RNA processes. With regard to cancer treatment, however, a search of Medline indicates that most antibiotics are used against bacterial infections incurred during cancer treatment. An exception involves studies at the M.D. Anderson Cancer Center of the University of Texas, located in Houston. These studies utilized actinomycin D and doxorubicin, both said to be known anticancer agents, in conjunction with the mitotic inhibitors vinblastine and Taxol. (The latter two are from plant extracts, and inhibit cell division or mitosis. The first-mentioned is derived from the Madagascar periwinkle [as is another alkaloid called vincristine], the latter from the yew tree of the... 

Drugs that disturb the assembly and disassembly of microtubules have been widely used to treat various diseases. Indeed, more than 2500 years ago, the ancient Egyptians treated heart problems with colchicine. Nowadays, this drug is used primarily in the treatment of gout and certain other diseases affecting the joints and skin. Other inhibitors of microtubule dynamics, including taxol, are effective anticancer agents and are used in the treatment of ovarian cancer. I... 

Kingston DGI, Samaranayake G, Ivey CA (1990) The Chemistry of Taxol, a Clinically Useful Anticancer Agent. J Nat Prod 53 1... 

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