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;
PubChemCID	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	276.508g·mol−1
	Except where otherwise noted, data are given for materials in theirstandard state(at 25 °C [77 °F], 100 kPa). Infobox references

Taxanesare a class ofditerpenes.They were originally identified from plants of the genusTaxus(yews), and feature ataxadienecore.Paclitaxel(Taxol) anddocetaxel(Taxotere) are widely used aschemotherapyagents.^[2]^[3]Cabazitaxelwas FDA approved to treat hormone-refractoryprostate cancer.

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

Production

As their name suggests, taxanes were first derived from natural sources, but some have beensemisynthesized.Paclitaxel was originally derived from thePacific yewtree.^[4]^[5]Taxanes are difficult to synthesize because of their numerouschiralcentres—taxol has 11 of these.

Recently, the presence of taxanes in the shells and leaves ofCorylus 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 ofmicrotubulefunction. Microtubules are essential to cell division, and taxanes stabilizeGDP-boundtubulinin the microtubule, thereby inhibiting the process of cell division asdepolymerizationis prevented. Thus, in essence, taxanes aremitotic inhibitors.In contrast to the taxanes, thevinca alkaloidspreventmitotic spindleformation through inhibition oftubulinpolymerization.Both taxanes and vinca alkaloids are, therefore, namedspindle poisonsor mitosis poisons, but they act in different ways. Taxanes are also thought to beradiosensitizing.

Substances

Hongdoushans A–C are oxygenated taxane diterpenes, isolated from the wood ofTaxus wallichiana.Hongdoushan A (C₂₉H₄₄O₇), hongdoushan B (C₂₇H₄₀O₇), and hongdoushan C (C₂₇H₄₂O₆) are reported to have anticancer activityin vitro.^[8]TaxuspinesA–D have been isolated fromTaxus.^[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 assynonymouswithtaxoids.The name "taxol" began as a common noun (analogous with other terms in which a genus name root wassuffixedwith-olor-in), but it was later capitalized as a trade name, and theinternational nonproprietary nameof 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.PMC4161504.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 10417482fromPubChem
^CID 5321744fromPubChem
^CID 100991639fromPubChem
^CID 5321746fromPubChem

External links

Media related totaxanesat 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.PMC4161504.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 10417482fromPubChem

[10] CID 5321744fromPubChem

[11] CID 100991639fromPubChem

[12] CID 5321746fromPubChem

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