Parthenolide is a

sesquiterpene lactone Sesquiterpene lactones (SLs) are a class of sesquiterpenoids that contain a lactone ring. They are most often found in plants of the family Asteraceae (daisies, asters). Other plant families with SLs are Umbelliferae (celery, parsley, carrots) an ...

of the

germacranolide Germacranolides are a group of natural chemical compounds classified as sesquiterpene lactone Sesquiterpene lactones (SLs) are a class of sesquiterpenoids that contain a lactone ring. They are most often found in plants of the family Asteraceae ...

class which occurs naturally in the plant feverfew (''

Tanacetum parthenium ''Tanacetum parthenium'', known as feverfew, is a flowering plant in the daisy family, Asteraceae. It may be grown as an ornament, and may be identified by its synonyms, ''Chrysanthemum parthenium'' and ''Pyrethrum parthenium''. Description T ...

''), after which it is named, and in the closely related tansy (''

Tanacetum vulgare Tansy (''Tanacetum vulgare'') is a perennial, herbaceous flowering plant in the genus ''Tanacetum'' in the aster family, native to temperate Europe and Asia. It has been introduced to other parts of the world, including North America, and in ...

''). 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. Lack of

solubility In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solubil ...

in water and

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...

limits the potential of parthenolide as a drug.

''In vitro'' research

Parthenolide has a variety of reported ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

'' biological activities, including: *Inhibition of

HDAC1 Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the ''HDAC1'' gene. Function Histone acetylation and deacetylation, catalyzed by multisubunit complexes, play a key role in the regulation of eukaryotic gene expression. Th ...

protein without affecting other class I/II

HDAC Histone deacetylases (, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly. This is important because DNA is wrapped around h ...

s, which leads to sustained DNA damage response in certain cells (required for

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

). *Modulation of the

NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...

-mediated inflammatory responses in experimental atherosclerosis. *Inducing

acute myelogenous leukemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may includ ...

(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 cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...

s that give rise to AML. *Activity against ''

Leishmania amazonensis ''Leishmania amazonensis'' is a parasite responsible for the disease leishmaniasis. This species has been known to spread by using sandflies Sandfly (or sand fly) is a colloquial name for any species or genus of flying, biting, blood-suckin ...

''. *

Microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...

-interfering activity. *

Agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

of the

adiponectin receptor 2 Adiponectin receptor 2 (AdipoR2) is a protein which in humans is encoded by the ''ADIPOR2'' gene. It is a member of the progestin and adipoQ receptor (PAQR) family, and is also known as PAQR2. Structure Similar to G protein-coupled receptors (GPCR ...

(AdipoR2). * Inhibition of mammalian thioredoxin reductase

References

{{HDAC inhibitors Adiponectin receptor agonists Epoxides Histone deacetylase inhibitors Sesquiterpene lactones