Parthenolide

Parthenolide
Names
	IUPAC name (1aR,4E,7aS,10aS,10bR)-2,3,6,7,7a,8,10a,10b-octahydro-1a,5-dimethyl-8-methylene-oxireno[9,10]cyclodeca[1,2-b]furan-9(1aH)-one
Identifiers
CAS Number	20554-84-1;
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL540445;
ChemSpider	20126246;
ECHA InfoCard	100.220.558
PubChemCID	5420805;
RTECS number	LY4220000;
UNII	2RDB26I5ZB;
CompTox Dashboard(EPA)	DTXSID2040579;
	InChI InChI=1S/C15H20O3/c1-9-5-4-8-15(3)13(18-15)12-11(7-6-9)10(2)14(16)17-12/h5,11-13H,2,4,6-8H2,1,3H3/b9-5+/t11-,12-,13-,15+/m0/s1 Key: KTEXNACQROZXEV-SLXBATTESA-N; Key: KTEXNACQROZXEV-SLXBATTEBY; InChI=1/C15H20O3/c1-9-5-4-8-15(3)13(18-15)12-11(7-6-9)10(2)14(16)17-12/h5,11-13H,2,4,6-8H2,1,3H3/b9-5+/t11-,12-,13-,15+/m0/s1;
	SMILES C/C/1=C\CC[C@@]2([C@@H](O2)[C@@H]3[C@@H](CC1)C(=C)C(=O)O3)C;
Properties
Chemical formula	C15H20O3
Molar mass	248.322g·mol−1
Melting point	113 to 115 °C (235 to 239 °F; 386 to 388 K)
	Except where otherwise noted, data are given for materials in theirstandard state(at 25 °C [77 °F], 100 kPa). verify(what is?) Infobox references

Parthenolideis asesquiterpene lactoneof thegermacranolideclass which occurs naturally in the plant feverfew (Tanacetum parthenium), after which it is named, and in the closely related tansy (Tanacetum vulgare).^[1]It is found in highest concentration in the flowers and fruit. Parthenolide's molecular structure depiction is often incorrect regarding the stereochemistry of the epoxide, although X-ray single crystal structures are available.^[2]^[3]

Lack ofsolubilityin water andbioavailabilitylimits the potential of parthenolide as a drug.

In vitroresearch

Parthenolide has a variety of reportedin vitrobiological activities, including:

Inhibition ofHDAC1protein without affecting other class I/IIHDACs,which leads to sustained DNA damage response in certain cells (required forapoptosis).^[4]
Modulation of theNF-κB-mediated inflammatory responses in experimental atherosclerosis.^[5]
Inducingapoptosisinacute myelogenous leukemia(AML) cells, leaving normal bone marrow cells relatively unscathed. Moreover, the compound may get at the root of the disease because it also killsstem cellsthat give rise to AML.^[6]
Activity againstLeishmania amazonensis.^[7]
Microtubule-interfering activity.^[8]
Agonistof theadiponectin receptor 2(AdipoR2).^[9]
Inhibition of mammalian thioredoxin reductase^[10]

References

^Onozato, Thelma; Nakamura, Celso Vataru; Garcia Cortez, Diógenes Aparício; Dias Filho, Benedito Prado; Ueda-Nakamura, Tânia (2009)."Tanacetum vulgare: antiherpes virus activity of crude extract and the purified compound parthenolide".Phytother Res.23(6): 791–6.doi:10.1002/ptr.2638.PMID 19152371.S2CID 3547899.
^Quick, Andrew; Rogers, Donald (1976)."Crystal and molecular structure of parthenolide [4,5-epoxygermacra-1(10),11(13)-dien-12,6-olactone]".Journal of the Chemical Society, Perkin Transactions 2(4): 465.doi:10.1039/p29760000465.ISSN 0300-9580.
^Long, Jing; Ding, Ya-Hui; Wang, Pan-Pan; Zhang, Quan; Chen, Yue (2013-10-18)."Protection-Group-Free Semisyntheses of Parthenolide and Its Cyclopropyl Analogue".The Journal of Organic Chemistry.78(20): 10512–10518.doi:10.1021/jo401606q.ISSN 0022-3263.PMID 24047483.
^Rajendran P, Ho E, Williams DE, Dashwood RH (2011)."Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells".Clinical Epigenetics.3(1): 4.doi:10.1186/1868-7083-3-4.PMC3255482.PMID 22247744.
^López-Franco O, Hernández-Vargas P, Ortiz-Muñoz G, Sanjuán G, Suzuki Y, Ortega L, Blanco J, Egido J, Gómez-Guerrero C (August 2006)."Parthenolide modulates the NF-kappaB-mediated inflammatory responses in experimental atherosclerosis".Arteriosclerosis, Thrombosis, and Vascular Biology.26(8): 1864–70.doi:10.1161/01.ATV.0000229659.94020.53.PMID 16741149.
^Guzman ML, Rossi RM, Karnischky L, Li X, Peterson DR, Howard DS, Jordan CT (June 2005)."The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells".Blood.105(11): 4163–9.doi:10.1182/blood-2004-10-4135.PMC1895029.PMID 15687234.
^Tiuman TS, Ueda-Nakamura T, Garcia Cortez DA, Dias Filho BP, Morgado-Díaz JA, de Souza W, Nakamura CV (January 2005)."Antileishmanial activity of parthenolide, a sesquiterpene lactone isolated from Tanacetum parthenium".Antimicrobial Agents and Chemotherapy.49(1): 176–82.doi:10.1128/AAC.49.11.176-182.2005.PMC538891.PMID 15616293.
^Miglietta A, Bozzo F, Gabriel L, Bocca C (October 2004). "Microtubule-interfering activity of parthenolide".Chemico-Biological Interactions.149(2–3): 165–73.doi:10.1016/j.cbi.2004.07.005.PMID 15501437.
^Sun Y, Zang Z, Zhong L, Wu M, Su Q, Gao X, Zan W, Lin D, Zhao Y, Zhang Z (2013)."Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay".PLOS ONE.8(5): e63354.Bibcode:2013PLoSO...863354S.doi:10.1371/journal.pone.0063354.PMC3653934.PMID 23691032.
^Duan D, Zhang J, Yao J, Liu Y, Fang J (May 2016)."Targeting Thioredoxin Reductase by Parthenolide Contributes to Inducing Apoptosis of HeLa Cells".The Journal of Biological Chemistry.291(19): 10021–31.doi:10.1074/jbc.M115.700591.PMC4858956.PMID 27002142.

[1] Onozato, Thelma; Nakamura, Celso Vataru; Garcia Cortez, Diógenes Aparício; Dias Filho, Benedito Prado; Ueda-Nakamura, Tânia (2009)."Tanacetum vulgare: antiherpes virus activity of crude extract and the purified compound parthenolide".Phytother Res.23(6): 791–6.doi:10.1002/ptr.2638.PMID 19152371.S2CID 3547899.

[2] Quick, Andrew; Rogers, Donald (1976)."Crystal and molecular structure of parthenolide [4,5-epoxygermacra-1(10),11(13)-dien-12,6-olactone]".Journal of the Chemical Society, Perkin Transactions 2(4): 465.doi:10.1039/p29760000465.ISSN 0300-9580.

[3] Long, Jing; Ding, Ya-Hui; Wang, Pan-Pan; Zhang, Quan; Chen, Yue (2013-10-18)."Protection-Group-Free Semisyntheses of Parthenolide and Its Cyclopropyl Analogue".The Journal of Organic Chemistry.78(20): 10512–10518.doi:10.1021/jo401606q.ISSN 0022-3263.PMID 24047483.

[4] Rajendran P, Ho E, Williams DE, Dashwood RH (2011)."Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells".Clinical Epigenetics.3(1): 4.doi:10.1186/1868-7083-3-4.PMC3255482.PMID 22247744.

[5] López-Franco O, Hernández-Vargas P, Ortiz-Muñoz G, Sanjuán G, Suzuki Y, Ortega L, Blanco J, Egido J, Gómez-Guerrero C (August 2006)."Parthenolide modulates the NF-kappaB-mediated inflammatory responses in experimental atherosclerosis".Arteriosclerosis, Thrombosis, and Vascular Biology.26(8): 1864–70.doi:10.1161/01.ATV.0000229659.94020.53.PMID 16741149.

[6] Guzman ML, Rossi RM, Karnischky L, Li X, Peterson DR, Howard DS, Jordan CT (June 2005)."The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells".Blood.105(11): 4163–9.doi:10.1182/blood-2004-10-4135.PMC1895029.PMID 15687234.

[7] Tiuman TS, Ueda-Nakamura T, Garcia Cortez DA, Dias Filho BP, Morgado-Díaz JA, de Souza W, Nakamura CV (January 2005)."Antileishmanial activity of parthenolide, a sesquiterpene lactone isolated from Tanacetum parthenium".Antimicrobial Agents and Chemotherapy.49(1): 176–82.doi:10.1128/AAC.49.11.176-182.2005.PMC538891.PMID 15616293.

[8] Miglietta A, Bozzo F, Gabriel L, Bocca C (October 2004). "Microtubule-interfering activity of parthenolide".Chemico-Biological Interactions.149(2–3): 165–73.doi:10.1016/j.cbi.2004.07.005.PMID 15501437.

[pmid23691032-9] Sun Y, Zang Z, Zhong L, Wu M, Su Q, Gao X, Zan W, Lin D, Zhao Y, Zhang Z (2013)."Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay".PLOS ONE.8(5): e63354.Bibcode:2013PLoSO...863354S.doi:10.1371/journal.pone.0063354.PMC3653934.PMID 23691032.

[pmid27002142-10] Duan D, Zhang J, Yao J, Liu Y, Fang J (May 2016)."Targeting Thioredoxin Reductase by Parthenolide Contributes to Inducing Apoptosis of HeLa Cells".The Journal of Biological Chemistry.291(19): 10021–31.doi:10.1074/jbc.M115.700591.PMC4858956.PMID 27002142.

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