Taxane

Taxane
Names
	IUPAC name Taxane
	Systematic IUPAC name (4R,4aR,6S,9R,10S,12aS)-4,9,12a,13,13-Pentamethyltetradecahydro-6,10-methanobenzo[10]annulene
Identifiers
CAS Number	1605-68-1;
3D model (JSmol)	Interactive image;
ChemSpider	7827751;
PubChem CID	9548828;
	InChI InChI=1S/C20H36/c1-14-7-6-11-20(5)12-10-17-15(2)8-9-16(13-18(14)20)19(17,3)4/h14-18H,6-13H2,1-5H3/t14-,15-,16+,17+,18-,20+/m1/s1 Key: DKPFODGZWDEEBT-QFIAKTPHSA-N; InChI=1S/C20H36/c1-14-7-6-11-20(5)12-10-17-15(2)8-9-16(13-18(14)20)19(17,3)4/h14-18H,6-13H2,1-5H3/t14-,15-,16+,17+,18-,20+/m1/s1 Key: DKPFODGZWDEEBT-QFIAKTPHSA-N;
	SMILES C[C@@H]1CCC[C@@]2([C@@H]1C[C@@H]3CC[C@H]([C@@H](C3(C)C)CC2)C)C;
Properties
Chemical formula	C20H36
Molar mass	276.508 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Taxanes are a class of 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.^[2]^[3] 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 semisynthesized. Paclitaxel was originally derived from the Pacific yew tree.^[4]^[5] Taxanes are difficult to synthesize because of their numerous chiral centres—taxol has 11 of these.

Recently, the presence of taxanes in the shells and leaves of Corylus avellana (the common hazel plant) has been reported.^[6]^[7]

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 polymerization. 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.^[8] Taxuspines A–D have been isolated from Taxus.^[9]^[10]^[11]^[12]

Baccatin III (left) Paclitaxel (right)

10-Deacetylbaccatin (left) Docetaxel (right)

Taxuspine A

Taxuspine B

Hongdoushan A

Names

Taxanes are usually treated as synonymous with taxoids. The name "taxol" began as a common noun (analogous with other terms in which a genus name root was suffixed with -ol or -in), but it was later capitalized as a trade name, and the international nonproprietary name of the compound is paclitaxel.

References

^ International Union of Pure and Applied Chemistry (2014). Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013. The Royal Society of Chemistry. p. 1540. doi:10.1039/9781849733069. ISBN 978-0-85404-182-4.
^ Hagiwara, H.; Sunada, Y. (2004). "Mechanism of taxane neurotoxicity". Breast Cancer (Tokyo, Japan). 11 (1): 82–85. doi:10.1007/BF02968008. PMID 14718798. S2CID 22096988.
^ 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. PMID 9046968.
^ Hacker, Miles (2009). "Adverse Drug Reactions". Pharmacology. pp. 327–352. doi:10.1016/B978-0-12-369521-5.00013-0. ISBN 9780123695215.
^ Weaver, Beth A.; Bement, William (2014). "How Taxol/paclitaxel kills cancer cells". Molecular Biology of the Cell. 25 (18): 2677–2681. doi:10.1091/mbc.e14-04-0916. ISSN 1059-1524. PMC 4161504. PMID 25213191.
^ Ottaggio, Laura; Bestoso, Federica; Armirotti, Andrea; Balbi, Alessandro; Damonte, Gianluca; Mazzei, Mauro; Sancandi, Monica; Miele, Mariangela (2008). "Taxanes from Shells and Leaves of Corylus avellana". Journal of Natural Products. 71 (1): 58–60. doi:10.1021/np0704046. PMID 18163585.
^ Hoffman, Angela M; Shahidi, Fereidoon (January 2009). "Paclitaxel and other taxanes in hazel". Journal of Functional Foods. 1 (1): 33–37. doi:10.1016/j.jff.2008.09.004.
^ 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.
^ CID 10417482 from PubChem
^ CID 5321744 from PubChem
^ CID 100991639 from PubChem
^ CID 5321746 from PubChem

External links

Media related to taxanes at Wikimedia Commons

[1] International Union of Pure and Applied Chemistry (2014). Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013. The Royal Society of Chemistry. p. 1540. doi:10.1039/9781849733069. ISBN 978-0-85404-182-4.

[2] Hagiwara, H.; Sunada, Y. (2004). "Mechanism of taxane neurotoxicity". Breast Cancer (Tokyo, Japan). 11 (1): 82–85. doi:10.1007/BF02968008. PMID 14718798. S2CID 22096988.

[3] 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. PMID 9046968.

[Hacker2009-4] Hacker, Miles (2009). "Adverse Drug Reactions". Pharmacology. pp. 327–352. doi:10.1016/B978-0-12-369521-5.00013-0. ISBN 9780123695215.

[WeaverBement2014-5] Weaver, Beth A.; Bement, William (2014). "How Taxol/paclitaxel kills cancer cells". Molecular Biology of the Cell. 25 (18): 2677–2681. doi:10.1091/mbc.e14-04-0916. ISSN 1059-1524. PMC 4161504. PMID 25213191.

[6] Ottaggio, Laura; Bestoso, Federica; Armirotti, Andrea; Balbi, Alessandro; Damonte, Gianluca; Mazzei, Mauro; Sancandi, Monica; Miele, Mariangela (2008). "Taxanes from Shells and Leaves of Corylus avellana". Journal of Natural Products. 71 (1): 58–60. doi:10.1021/np0704046. PMID 18163585.

[7] Hoffman, Angela M; Shahidi, Fereidoon (January 2009). "Paclitaxel and other taxanes in hazel". Journal of Functional Foods. 1 (1): 33–37. doi:10.1016/j.jff.2008.09.004.

[pmid12444707-8] 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.

[9] CID 10417482 from PubChem

[10] CID 5321744 from PubChem

[11] CID 100991639 from PubChem

[12] CID 5321746 from PubChem

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Names

IUPAC name Taxane^[1]
Systematic IUPAC name (4R,4aR,6S,9R,10S,12aS)-4,9,12a,13,13-Pentamethyltetradecahydro-6,10-methanobenzo[10]annulene
Identifiers
CAS Number	1605-68-1
3D model (JSmol)	Interactive image
ChemSpider	7827751
PubChem CID	9548828
InChI InChI=1S/C20H36/c1-14-7-6-11-20(5)12-10-17-15(2)8-9-16(13-18(14)20)19(17,3)4/h14-18H,6-13H2,1-5H3/t14-,15-,16+,17+,18-,20+/m1/s1 Key: DKPFODGZWDEEBT-QFIAKTPHSA-N InChI=1S/C20H36/c1-14-7-6-11-20(5)12-10-17-15(2)8-9-16(13-18(14)20)19(17,3)4/h14-18H,6-13H2,1-5H3/t14-,15-,16+,17+,18-,20+/m1/s1 Key: DKPFODGZWDEEBT-QFIAKTPHSA-N
SMILES C[C@@H]1CCC[C@@]2([C@@H]1C[C@@H]3CC[C@H]([C@@H](C3(C)C)CC2)C)C
Properties
Chemical formula	C₂₀H₃₆
Molar mass	276.508 g·mol⁻¹
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references