Parthenolide
Appearance
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Names | |
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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
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3D model (JSmol)
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ChEMBL | |
ChemSpider | |
ECHA InfoCard | 100.220.558 |
PubChemCID
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CompTox Dashboard(EPA)
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Properties | |
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).
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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
[edit]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
[edit]- ^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.PMID19152371.S2CID3547899.
- ^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.ISSN0300-9580.
- ^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.ISSN0022-3263.PMID24047483.
- ^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.PMID22247744.
- ^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.PMID16741149.
- ^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.PMID15687234.
- ^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.PMID15616293.
- ^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.PMID15501437.
- ^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.PMID23691032.
- ^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.PMID27002142.