Taxane

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Baccatin III (left) Paclitaxel (right)

Taxanes are diterpenes. They were originally identified from plants of the genus Taxus (yews), and feature a taxadiene core. Paclitaxel (Taxol) and docetaxel (Taxotere) are widely used as chemotherapy agents.[1][2] Cabazitaxel was FDA approved to treat hormone-refractory prostate cancer.

Taxanes present difficulties in formulation as medicines because they are poorly soluble in water.

Production

As their name suggests, taxanes were first derived from natural sources, but some have been synthesized artificially. Paclitaxel was originally derived from the Pacific yew tree. Taxanes are difficult to synthesize because of their numerous chiral centres — Taxol has 11 of these.

Mechanism of action

The principal mechanism of action of the taxane class of drugs is the disruption of microtubule function. Microtubules are essential to cell division, and taxanes stabilize GDP-bound tubulin in the microtubule, thereby inhibiting the process of cell division as depolymerization is prevented. Thus, in essence, taxanes are mitotic inhibitors. In contrast to the taxanes, the vinca alkaloids prevent mitotic spindle formation through inhibition of tubulin polymerisation. Both taxanes and vinca alkaloids are, therefore, named spindle poisons or mitosis poisons, but they act in different ways. Taxanes are also thought to be radiosensitizing.

Substances

Hongdoushans A-C are oxygenated taxane diterpenes, isolated from the wood of Taxus wallichiana. Hongdoushan A (C29H44O7), hongdoushan B (C27H40O7), and hongdoushan C (C27H42O6) are reported to have anticancer activity in vitro.[3]

See also

References

  1. ↑ Hagiwara, H.; Sunada, Y. (2004). "Mechanism of taxane neurotoxicity". Breast cancer (Tokyo, Japan) 11 (1): 82–85. PMID 14718798.
  2. ↑ Rowinsky, MD, Eric K. (February 1997). "THE DEVELOPMENT AND CLINICAL UTILITY OF THE TAXANE CLASS OF ANTIMICROTUBULE CHEMOTHERAPY AGENTS". Annual Review of Medicine 48 (1): 353–374. doi:10.1146/annurev.med.48.1.353.
  3. ↑ Banskota AH, Usia T, Tezuka Y, Kouda K, Nguyen NT, Kadota S (2002). "Three new C-14 oxygenated taxanes from the wood of Taxus yunnanensis.". J Nat Prod 65 (11): 1700–2. doi:10.1021/np020235j. PMID 12444707.

External links


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