Genistein

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Genistein

Names
IUPAC name 4′,5,7-Trihydroxyisoflavone
Systematic IUPAC name 5,7-Dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one
Identifiers
CAS Number	446-72-0 Y
3D model (JSmol)	Interactive image
Beilstein Reference	263823
ChEBI	CHEBI:28088 Y
ChEMBL	ChEMBL44 Y
ChemSpider	4444448 Y
DrugBank	DB01645 Y
ECHA InfoCard	100.006.524
EC Number	207-174-9
IUPHAR/BPS	2826
KEGG	D11680 Y C06563
PubChem CID	5280961
UNII	DH2M523P0H Y
CompTox Dashboard (EPA)	DTXSID5022308
InChI InChI=1S/C15H10O5/c16-9-3-1-8(2-4-9)11-7-20-13-6-10(17)5-12(18)14(13)15(11)19/h1-7,16-18H Y Key: TZBJGXHYKVUXJN-UHFFFAOYSA-N Y InChI=1/C15H10O5/c16-9-3-1-8(2-4-9)11-7-20-13-6-10(17)5-12(18)14(13)15(11)19/h1-7,16-18H Key: TZBJGXHYKVUXJN-UHFFFAOYAH
SMILES Oc1ccc(cc1)C\3=C\Oc2cc(O)cc(O)c2C/3=O
Properties
Chemical formula	C15H10O5
Molar mass	270.240 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is YN ?) Infobox references

Genistein (C₁₅H₁₀O₅) is a naturally occurring compound that structurally belongs to a class of compounds known as isoflavones. It is described as an angiogenesis inhibitor and a phytoestrogen.^[1]

It was first isolated in 1899 from the dyer's broom, Genista tinctoria; hence, the chemical name. The compound structure was established in 1926, when it was found to be identical with that of prunetol. It was chemically synthesized in 1928.^[2] It has been shown to be the primary secondary metabolite of the Trifolium species and Glycine max.^[3]

Isoflavones such as genistein and daidzein are found in a number of plants including lupin, fava beans, soybeans, kudzu, and psoralea being the primary food source,^[4][5] also in the medicinal plants, Flemingia vestita^[6] and F. macrophylla,^[7][8] and coffee.^[9] It can also be found in Maackia amurensis cell cultures.^[10]

Besides functioning as an antioxidant and anthelmintic, many isoflavones have been shown to interact with animal and human estrogen receptors, causing effects in the body similar to those caused by the hormone estrogen. Isoflavones also produce non-hormonal effects.^{[citation needed]}

Genistein influences multiple biochemical functions in living cells:

• full agonist of ERβ (EC₅₀ = 7.62 nM) and, to a much lesser extent (~20-fold), full agonist^[11] or partial agonist of ERα^[12]
• agonist of G protein-coupled estrogen receptor (affinity of 133 nM)^[13][14]
• activation of peroxisome proliferator-activated receptors (PPARs)
• inhibition of several tyrosine kinases
• inhibition of topoisomerase
• inhibition of AAAD
• direct antioxidation with some pro oxidative features
• activation of Nrf2 antioxidative response
• stimulation of autophagy^[15][16][17]
• inhibition of the mammalian hexose transporter GLUT1
• contraction of several types of smooth muscles
• modulation of CFTR channel, potentiating its opening at low concentration and inhibiting it a higher doses.
• inhibition of cytosine methylation
• inhibition of DNA methyltransferase^[18]
• inhibition of the glycine receptor
• inhibition of the nicotinic acetylcholine receptor^[19]

Isoflavones genistein and daidzein bind to and transactivate all three PPAR isoforms, α, δ, and γ.^[20] For example, membrane-bound PPARγ-binding assay showed that genistein can directly interact with the PPARγ ligand binding domain and has a measurable Ki of 5.7 mM.^[21] Gene reporter assays showed that genistein at concentrations between 1 and 100 uM activated PPARs in a dose dependent way in KS483 mesenchymal progenitor cells, breast cancer MCF-7 cells, T47D cells and MDA-MD-231 cells, murine macrophage-like RAW 264.7 cells, endothelial cells and in Hela cells. Several studies have shown that both ERs and PPARs influenced each other and therefore induce differential effects in a dose-dependent way. The final biological effects of genistein are determined by the balance among these pleiotrophic actions.^[20][22][23]

The main known activity of genistein is tyrosine kinase inhibitor, mostly of epidermal growth factor receptor (EGFR). Tyrosine kinases are less widespread than their ser/thr counterparts but implicated in almost all cell growth and proliferation signal cascades.^{[citation needed]}

Genistein may act as direct antioxidant, similar to many other isoflavones, and thus may alleviate damaging effects of free radicals in tissues.^[24][25]

The same molecule of genistein, similar to many other isoflavones, by generation of free radicals poison topoisomerase II, an enzyme important for maintaining DNA stability.^[26][27][28]

Human cells turn on beneficial, detoxifying Nrf2 factor in response to genistein insult. This pathway may be responsible for observed health maintaining properties of small doses of genistein.^[29]

The root-tuber peel extract of the leguminous plant Flemingia vestita is the traditional anthelmintic of the Khasi tribes of India. While investigating its anthelmintic activity, genistein was found to be the major isoflavone responsible for the deworming property.^[6][30] Genistein was subsequently demonstrated to be highly effective against intestinal parasites such as the poultry cestode Raillietina echinobothrida,^[30] the pork trematode Fasciolopsis buski,^[31] and the sheep liver fluke Fasciola hepatica.^[32] It exerts its anthelmintic activity by inhibiting the enzymes of glycolysis and glycogenolysis,^[33][34] and disturbing the Ca2+ homeostasis and NO activity in the parasites.^[35][36] It has also been investigated in human tapeworms such as Echinococcus multilocularis and E. granulosus metacestodes that genistein and its derivatives, Rm6423 and Rm6426, are potent cestocides.^[37]

Genistein protects against pro-inflammatory factor-induced vascular endothelial barrier dysfunction and inhibits leukocyte-endothelium interaction, thereby modulating vascular inflammation, a major event in the pathogenesis of atherosclerosis.^[38]

Genistein and other isoflavones have been identified as angiogenesis inhibitors, and found to inhibit the uncontrolled cell growth of cancer, most likely by inhibiting the activity of substances in the body that regulate cell division and cell survival (growth factors). Various studies have found that moderate doses of genistein have inhibitory effects on cancers of the prostate,^[39][40] cervix,^[41] brain,^[42] breast^[39][43][44] and colon.^[17] It has also been shown that genistein makes some cells more sensitive to radio-therapy.