parthenolide
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| ImageFile = Parthenolide.svg
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| IUPACName = (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
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| CASNo = 20554-84-1
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| PubChem = 5420805
| RTECS = LY4220000
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| UNII = 2RDB26I5ZB
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| ChEMBL = 540445
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| ChemSpiderID = 20126246
| SMILES = C/C/1=C\CC[C@@]2([C@@H](O2)[C@@H]3[C@@H](CC1)C(=C)C(=O)O3)C
| InChI2 = 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
| InChIKey = KTEXNACQROZXEV-SLXBATTEBY
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| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = KTEXNACQROZXEV-SLXBATTESA-N}}
| Section2 = {{Chembox Properties
| C=15|H=20|O=3
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| MeltingPtC = 113 to 115
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| Section6 = {{Chembox Explosive
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| Section9 = {{Chembox Related
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Parthenolide is a sesquiterpene lactone of the germacranolide class which occurs naturally in the plant feverfew (Tanacetum parthenium), after which it is named, and in the closely related tansy (Tanacetum vulgare).{{cite journal |last1=Onozato |first1=Thelma |last2=Nakamura |first2=Celso Vataru |last3=Garcia Cortez |first3=Diógenes Aparício|last4=Dias Filho |first4=Benedito Prado |last5=Ueda-Nakamura |first5=Tânia |title=Tanacetum vulgare: antiherpes virus activity of crude extract and the purified compound parthenolide |journal=Phytother Res |date=2009 |volume=23 |issue=6 |pages=791–6 |doi=10.1002/ptr.2638 |pmid=19152371 |s2cid=3547899 |doi-access=free }} 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.{{Cite journal|last1=Quick|first1=Andrew|last2=Rogers|first2=Donald|date=1976|title=Crystal and molecular structure of parthenolide [4,5-epoxygermacra-1(10),11(13)-dien-12,6-olactone]|url=http://xlink.rsc.org/?DOI=p29760000465|journal=Journal of the Chemical Society, Perkin Transactions 2|language=en|issue=4|pages=465|doi=10.1039/p29760000465|issn=0300-9580}}{{Cite journal|last1=Long|first1=Jing|last2=Ding|first2=Ya-Hui|last3=Wang|first3=Pan-Pan|last4=Zhang|first4=Quan|last5=Chen|first5=Yue|date=2013-10-18|title=Protection-Group-Free Semisyntheses of Parthenolide and Its Cyclopropyl Analogue|url=http://pubs.acs.org/doi/10.1021/jo401606q|journal=The Journal of Organic Chemistry|language=en|volume=78|issue=20|pages=10512–10518|doi=10.1021/jo401606q|pmid=24047483|issn=0022-3263}}
Lack of solubility in water and bioavailability limits the potential of parthenolide as a drug.
''In vitro'' research
Parthenolide has a variety of reported in vitro biological activities, including:
- Inhibition of HDAC1 protein without affecting other class I/II HDACs, which leads to sustained DNA damage response in certain cells (required for apoptosis).{{cite journal | vauthors = Rajendran P, Ho E, Williams DE, Dashwood RH | title = Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells | journal = Clinical Epigenetics | volume = 3 | issue = 1 | pages = 4 | year = 2011 | pmid = 22247744 | pmc = 3255482 | doi = 10.1186/1868-7083-3-4 | doi-access = free }}
- Modulation of the NF-κB-mediated inflammatory responses in experimental atherosclerosis.{{cite journal | vauthors = López-Franco O, Hernández-Vargas P, Ortiz-Muñoz G, Sanjuán G, Suzuki Y, Ortega L, Blanco J, Egido J, Gómez-Guerrero C | title = Parthenolide modulates the NF-kappaB-mediated inflammatory responses in experimental atherosclerosis | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 26 | issue = 8 | pages = 1864–70 | date = August 2006 | pmid = 16741149 | doi = 10.1161/01.ATV.0000229659.94020.53 | doi-access = free }}
- Inducing apoptosis in acute 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 kills stem cells that give rise to AML.{{cite journal | vauthors = Guzman ML, Rossi RM, Karnischky L, Li X, Peterson DR, Howard DS, Jordan CT | title = The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells | journal = Blood | volume = 105 | issue = 11 | pages = 4163–9 | date = June 2005 | pmid = 15687234 | pmc = 1895029 | doi = 10.1182/blood-2004-10-4135 }}
- Activity against Leishmania amazonensis.{{cite journal | vauthors = Tiuman TS, Ueda-Nakamura T, Garcia Cortez DA, Dias Filho BP, Morgado-Díaz JA, de Souza W, Nakamura CV | title = Antileishmanial activity of parthenolide, a sesquiterpene lactone isolated from Tanacetum parthenium | journal = Antimicrobial Agents and Chemotherapy | volume = 49 | issue = 1 | pages = 176–82 | date = January 2005 | pmid = 15616293 | pmc = 538891 | doi = 10.1128/AAC.49.11.176-182.2005 }}
- Microtubule-interfering activity.{{cite journal | vauthors = Miglietta A, Bozzo F, Gabriel L, Bocca C | title = Microtubule-interfering activity of parthenolide | journal = Chemico-Biological Interactions | volume = 149 | issue = 2–3 | pages = 165–73 | date = October 2004 | pmid = 15501437 | doi = 10.1016/j.cbi.2004.07.005 }}
- Agonist of the adiponectin receptor 2 (AdipoR2).{{cite journal | vauthors = Sun Y, Zang Z, Zhong L, Wu M, Su Q, Gao X, Zan W, Lin D, Zhao Y, Zhang Z | title = Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay | journal = PLOS ONE | volume = 8 | issue = 5 | pages = e63354 | year = 2013 | pmid = 23691032 | pmc = 3653934 | doi = 10.1371/journal.pone.0063354 | bibcode = 2013PLoSO...863354S | doi-access = free }}
- Inhibition of mammalian thioredoxin reductase {{cite journal | vauthors = Duan D, Zhang J, Yao J, Liu Y, Fang J | title = Targeting Thioredoxin Reductase by Parthenolide Contributes to Inducing Apoptosis of HeLa Cells | journal = The Journal of Biological Chemistry | volume = 291 | issue = 19 | pages = 10021–31 | date = May 2016 | pmid = 27002142 | pmc = 4858956 | doi = 10.1074/jbc.M115.700591 | doi-access = free }}
References
{{Reflist}}
{{HDAC inhibitors}}
Category:Adiponectin receptor agonists