Parthenolide Explained

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).^[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 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).^[4]
• Modulation of the NF-κB-mediated inflammatory responses in experimental atherosclerosis.^[5]
• 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.^[6]
• Activity against Leishmania amazonensis.^[7]
• Microtubule-interfering activity.^[8]
• Agonist of the adiponectin receptor 2 (AdipoR2).^[9]
• Inhibition of mammalian thioredoxin reductase ^[10]

Notes and References

1. Onozato . Thelma . Nakamura . Celso Vataru . Garcia Cortez . Diógenes Aparício. Dias Filho . Benedito Prado . Ueda-Nakamura . Tânia . Tanacetum vulgare: antiherpes virus activity of crude extract and the purified compound parthenolide . Phytother Res . 2009 . 23 . 6 . 791–6 . 10.1002/ptr.2638 . 19152371 . 3547899 . free .
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. en. 4. 465. 10.1039/p29760000465. 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. en. 78. 20. 10512–10518. 10.1021/jo401606q. 24047483. 0022-3263.
4. Rajendran P, Ho E, Williams DE, Dashwood RH . Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells . Clinical Epigenetics . 3 . 1 . 4 . 2011 . 22247744 . 3255482 . 10.1186/1868-7083-3-4 . free .
5. López-Franco O, Hernández-Vargas P, Ortiz-Muñoz G, Sanjuán G, Suzuki Y, Ortega L, Blanco J, Egido J, Gómez-Guerrero C . Parthenolide modulates the NF-kappaB-mediated inflammatory responses in experimental atherosclerosis . Arteriosclerosis, Thrombosis, and Vascular Biology . 26 . 8 . 1864–70 . August 2006 . 16741149 . 10.1161/01.ATV.0000229659.94020.53 . free .
6. Guzman ML, Rossi RM, Karnischky L, Li X, Peterson DR, Howard DS, Jordan CT . The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells . Blood . 105 . 11 . 4163–9 . June 2005 . 15687234 . 1895029 . 10.1182/blood-2004-10-4135 .
7. Tiuman TS, Ueda-Nakamura T, Garcia Cortez DA, Dias Filho BP, Morgado-Díaz JA, de Souza W, Nakamura CV . Antileishmanial activity of parthenolide, a sesquiterpene lactone isolated from Tanacetum parthenium . Antimicrobial Agents and Chemotherapy . 49 . 1 . 176–82 . January 2005 . 15616293 . 538891 . 10.1128/AAC.49.11.176-182.2005 .
8. Miglietta A, Bozzo F, Gabriel L, Bocca C . Microtubule-interfering activity of parthenolide . Chemico-Biological Interactions . 149 . 2–3 . 165–73 . October 2004 . 15501437 . 10.1016/j.cbi.2004.07.005 .
9. Sun Y, Zang Z, Zhong L, Wu M, Su Q, Gao X, Zan W, Lin D, Zhao Y, Zhang Z . Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay . PLOS ONE . 8 . 5 . e63354 . 2013 . 23691032 . 3653934 . 10.1371/journal.pone.0063354 . 2013PLoSO...863354S . free .
10. Duan D, Zhang J, Yao J, Liu Y, Fang J . Targeting Thioredoxin Reductase by Parthenolide Contributes to Inducing Apoptosis of HeLa Cells . The Journal of Biological Chemistry . 291 . 19 . 10021–31 . May 2016 . 27002142 . 4858956 . 10.1074/jbc.M115.700591 . free .