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Quercetin

Names
IUPAC name 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one
Other names Sophoretin Meletin Quercetine Xanthaurine Quercetol Quercitin Quertine Flavin meletin
Identifiers
CAS Number	117-39-5 Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:16243 N
ChEMBL	ChEMBL50 Y
ChemSpider	4444051 Y
DrugBank	DB04216 N
KEGG	C00389 Y
PubChem CID	5280343
UNII	9IKM0I5T1E Y
InChI InChI=1S/C15H10O7/c16-7-4-10(19)12-11(5-7)22-15(14(21)13(12)20)6-1-2-8(17)9(18)3-6/h1-5,16-19,21H Y Key: REFJWTPEDVJJIY-UHFFFAOYSA-N Y InChI=1/C15H10O7/c16-7-4-10(19)12-11(5-7)22-15(14(21)13(12)20)6-1-2-8(17)9(18)3-6/h1-5,16-19,21H Key: REFJWTPEDVJJIY-UHFFFAOYAW
SMILES O=C1c3c(O/C(=C1/O)c2ccc(O)c(O)c2)cc(O)cc3O
Properties
Chemical formula	C15H10O7
Molar mass	302.236 g/mol
Appearance	yellow crystalline powder
Density	1.799 g/cm3
Melting point	316 °C
Solubility in water	Practically insoluble in water; soluble in aqueous alkaline solutions
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

Tracking categories (test):

• SizeSet

UV visible spectrum of quercetin, with lambda max at 369 nm.

Quercetin is the most common flavonoid in nature. It is found as its glycosylated forms such as quercitrin (3-rhamnosylquercetin) or rutoside (3-rhamnosy-glucosyl quercetin), specifically as a flavonol, which is a polyphenolic compound synthesized in plant cells. It exhibits antioxidant properties by reducing oxidative stress in cells via two distinct pathways: (1) radical scavenging activities and binding of transition metal ions and (2) competitively inhibiting xanthine oxidase (XOD). Quercetin is familiarly used in traditional medicine to prevent or treat diseases such as cancer, cardiovascular and nervous diseases, obesity, and chronic inflammation. Quercetin is naturally found in fruits and vegetables, especially onions, citrus and apples. Other sources include dark berries, grapes and olive oil. Green tea and red wine because of their high percentage of antioxidants and flavonoids have been identified as having prominent amounts of quercetin.

Properties

Antioxidant

Antioxidants are molecules that protect against the chain reaction known as oxidative stress caused by free radicals and reactive oxygen species (ROS). They give free radicals the electron they are searching for, stabilizing them before they damage essential macromolecules, such as DNA, proteins, lipids and carbohydrates. Quercetin has antioxidant properties exhibiting radical-scavenging activities that aid in the process of removing free radicals in biological organisms. The reductive properties of quercetin are attributed to the two phenolic hydroxyl groups, known as catechol group, which function as electron donating groups that are capable of being oxidized by free radicals. In addition, quercetin is classified as an antioxidant because it is capable of competitively inhibiting oxidative enzymes, such as xanthine oxidase, which generates superoxide molecules as a byproduct of converting xanthine to uric acid in the purine catabolic pathway, playing a key role in initiating radical-induced cellular damage in biological organisms. Quercetin's antioxidant properties allow it to specifically inhibit lipid peroxidation. As more in vitro studies are performed, there is increasing evidence that quercetin, as an antioxidant, protects cellular structures against oxidative damage and therefore, it can limit the risk of various degenerative diseases, such as, Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis, correlated to oxidative stress.

Pro-oxidant

Pro-oxidants are molecules that promote oxidative stress by producing free radicals in a system and/or inhibiting antioxidant mechanisms. Studies have shown that quercetin has the potential to exhibit pro-oxidant properties and therefore cytotoxic effects on cells, depending on concentration and free radical source. The enzymatically catalyzed oxidative degradation of quercetin produces o-semiquinone and o-quinone. o-semiquinone expedites the formation of superoxide while simultaneously decreasing glutathione (GSH). o-quinone's function is to increase the semiquinone supply in the reaction, therefore magnifying the pro-oxidative effect of quercetin.

Biosynthesis

Quercetin is an organic compound chemically classified as a hydrocarbon, specifically as a flavonol. Quercetin is biosynthesized from dihydroquercetin, a type of flavonol that participates in a reaction catalyzed by flavonol synthase. Flavanols have a 2-hydroxyflavone (IUPAC name: 3-hydroxy-2-phenylchromen-4-one) general backbone structure and quercetin is distinguished from other flavonols by the distinct positioning of the two phenolic -OH groups giving it the structure 2-(3,4-dihydroxyphenyl)- 3,5,7-trihydroxy-4H-chromen-4-one. The nonpolar properties of quercetin are attributed to the hydrophobic, co-coplanar structure of the molecule, which becomes more soluble in an aqueous solution when the hydroxyl groups are substituted with sugars.

Pathway

The following steps details the biosynthesis pathway for quercetin in model plants, specifically, snapdragon, Arabidopsis, maize, and petunia.

Step 1: Phenylalanine is converted to para-coumaryl CoA in a series of steps known as the general phenylpropanoid pathway using phenylalanine ammonia-lyase, cinnamate-4-hydroxylase, and 4-coumaroyl-CoA-ligase.

Step 2: Chalcone synthase, a type III polyketide synthase, catalyzes the condensation of para-coumaryl CoA and three malonyl-CoA thioesters to give chalcone.

Step 3: Chalcone isomerase catalyzes the intramolecular cyclization of chalcone to give (2S)-naringenin, a flavanone derivative of many flavonoids.

Step 4: Flavanone 3β-hydroxylase (FHT) catalyzes the B-ring hydroxylation of naringenin to produce dihydrokaempferol, a type of dihydroflavanol.

Step 5: Dihydrokaempferol is converted to dihydroquercetin by the actions of Flavonoid 3′-hydroxylase.

Step 6: Flavonol synthase catalyzes the conversion of dihydroquercetin into quercetin.

Clinical Relevance

Anti-Cancer activity

Due to its antioxidant, anti-tumor and anti-inflammatory activity, quercetin has been studied extensively as a chemoprevention agent in several cancer models, since it is thought to prevent tumor angiogenesis. Studies suggest that quercetin slow down the growth of cancer cells and help promote apoptosis.In breast cancer cell lines, quercetin was able to inhibit the expression of mutant p53 protein to levels that were almost undetectable. By inhibiting the expression of p53 the cells arrest the cell cycle at the G2-M cell cycle check point and stop dividing. Quercetin is able to inhibit production of heat shock proteins in many malignant cell lines such as breast cancer, leukemia, and colon cancer. Heat shock proteins allow tumor cells to bypass normal mechanisms of cell cycle arrest by forming a complex with mutant p53 and allows for an increased survival rate of cancer cells under different bodily stresses such as low circulation and high fever.

Anti-Inflammatory activity

By inhibiting the cofactor recruitment at the chromatin of pro-inflammatory genes, quercetin exerts its anti-inflammatory effects in epithelial cells. Studies suggest that quercetin can help stabilize the cells that release histamine in the body and therefore have an anti-inflammatory effect. At high concentrations, quercetin, mainly because of its catechol group, was shown to block both the cyclooxygenase and lipooxygenase activity, both which are responsible for the inflammatory effect in cells.

Fate in vivo

Following dietary ingestion, quercetin undergoes rapid and extensive metabolism that makes the biological effects presumed from in vitro studies unlikely to apply in vivo. Rodents that were intravenously administered with the Quercetin Aglycone showed a rapid decrease in plasma quercetin concentrations and a lack of accumulation of quercetin in the tissues. These results suggest that quercetin is quickly metabolized and excreted into urine following an intravenous injection of the compound in rodents.

Side Notes

Since quercetin is still being studied extensively in vitro, it has not been confirmed scientifically as a specific therapeutic for any condition nor approved by any regulatory agency. The European Food Safety Authority evaluated possible health claims associated with consumption of quercetin, finding that no cause-and-effect relationship has been established for any physiological effect. Quercetin dietary supplements have been promoted for a claimed ability to prevent and treat cancer; however, according to the American Cancer society, "there is no reliable clinical evidence that quercetin can prevent or treat cancer in humans". Only when quercetin is studied extensively in vivo is that data gathered will lead to direct predictions on its role in the human body.

References

Category:Quercetin Category:Flavonoid antioxidants Category:Xanthine oxidase inhibitors Category:Experimental medical treatments