446-72-0 Usage
Chemical Description
Genistein and orobol are isoflavone bis-C-glycosides, while p-TsOH·H2O is para-toluenesulfonic acid monohydrate, Na2S2O3 is sodium thiosulfate, CHCl3 is chloroform, MeOH is methanol, and silica gel is a type of stationary phase used in column chromatography.
Uses
Used in Pharmaceutical Industry:
Genistein is used as a pharmaceutical secondary standard for application in quality control, providing a convenient and cost-effective alternative to the preparation of in-house working standards.
Used in Cancer Treatment:
Genistein is used as an antineoplastic agent, exhibiting cancer chemopreventive activity against various endocrine-dependent tumors such as breast, prostate, and other tumors. It inhibits protein-tyrosine kinase, topoisomerase-II, and induces cell differentiation, DNA fragmentation, apoptosis, and G2/M cell cycle arrest.
Used in Antifungal Applications:
Genistein is used as an antifungal agent, demonstrating antifungal properties.
Used in Blood Lipid-Lowering:
Genistein is used as a blood lipid-lowering agent, helping to regulate blood lipid levels.
Used in Anti-Estrogen Activity:
Genistein is used to fight against estrogen activity due to its phytoestrogen properties.
Used in Cosmetics Industry:
Genistein is used as an anti-aging agent in cosmetics, promoting collagen synthesis and providing UV-protection through its antioxidant activity.
Used in Enzyme Inhibition:
Genistein is used as a cytotoxic inhibitor of tyrosine kinase and topoisomerase II kinase, exhibiting specific inhibitory activity against these enzymes.
Used in Cell Signaling Inhibition:
Genistein is used as an inhibitor of protein tyrosine kinase (PTK), blocking the mitogenic effect mediated by EGF and insulin, and modulating various oncological signaling pathways.
Pharmacological effects
Genistein is a kind of polyphenols compound which can be found in soy and red clover and other plants with its molecular structure being similar to 17β-estradiol and having antioxidant activity and high affinity towards estrogen receptor. It can inhibit the activity of protein tyrosine kinase (PTK) and topoisomerase enzyme activity II with capability of inducing programmed cell death and improve the efficacy of anti-cancer drug as well as inhibit angiogenesis, and so on. It is one type of flavonoids (also called isoflavones) and is often found together with isoflavones called the isoflavones. They are all called soy isoflavones. Those benefits of these kinds of compounds on human health have been studied extensively and it is a promising cancer chemopreventive agent with significant impact on preventing cancer and other diseases. Genistein is the major phytoestrogens in the present study.
Plant Source: legume Genista (broom).
Clinical Applications: it can be used for female beauty care and prevention of blood diseases and cancer.
Genistein contains polyphenol structure with the hydrogen atoms in the phenolic hydroxyl group being prone to dissociate from external oxygen atom from the external interaction, leading to the formation of hydrogen ions to play reduction effect. This is the structure basis for the capability of the genistein of anti-oxidative and reductive. So those substances in food can fight against superoxide anion radicals, blocking the chain reaction of free radicals and play a role in anti-oxidation.
Genistein is not a hormone, but because it can bind to estrogen receptors and plays a weak estrogenic effect, it is called phytoestrogens. Because the activity of isoflavones is only 1/1000 of the estradiol which can competitively bind with estrogen receptors, exhibiting two-way adjustment with the resulting estrogenic effects of much lower harmful effects than estradiol and further with protective effect on then hormone related diseases such as menopause, osteoporosis, elevated blood lipids, etc; for patients of high levels of estrogen, it exhibits anti-estrogenic activity and can prevent breast cancer, endometriosis with two-way balance adjustment function.
Genistein, for the rat high cholesterol induced by TNT (trinitrotoluene) WR1339, has effect of lowering serum cholesterol and triglycerides with the effect on the later one being particularly significant.
This information is edited by Xiongfeng Dai from lookchem.
Physical and Chemical Properties
It appears as pale yellow dendritic needle-like powder with the melting point being 297 ℃-298 ℃; It is soluble in common organic solvents but almost insoluble in water. When being dissolved in dilute alkali, it will become yellow color.
Mechanism of action
Genistein may inhibit cancer cell growth by blocking enzymes required for cell growth. Genistein may decrease cardiovascular risk in postmenopausal women by interacting with the nuclear estrogen receptors to alter the transcription of cell specific genes. In randomized clinical trials, genistein was seen to increase the ratio of nitric oxide to endothelin and improved flow-mediated endothelium dependent vasodilation in healthy postmenopausal women. In addition, genistein may have beneficial effects on glucose metabolism by inhibiting islet tyrosine kinase activity as well as insulin release dependent on glucose and sulfonylurea. References https://www.drugbank.ca/drugs/DB01645
Mechanism of action
Genistein, an isoflavone isolated from soybeans, exhibits anticarcinogenic and antioxidant properties. Particularly, genistein has been shown to inhibit production of IL-6 and MAPK. Modulation to
these cellular events may help regulate and attenuate UVB-induced inflammatory damage to the skin. Moreover, genistein inhibits UV-induced oxidative DNA damage and blocks UV-induced expression of
c-fos and c-jun proto-oncogenes.
Health Benefits
Estrogenic effect The estrogenic activity of genistein has been confirmed in many studies. Of all the isoflavones, genistein has the strongest estrogenic activity. The estrogenic effect of genistein may explain its protective action against osteoporosis and its possible effect on body weight reductions. Genistein is also used to ease menopause symptoms, such as hot flushes. Antioxidant Genistein is a strong antioxidant. Genistein removes damaging free radicals and reduces lipid peroxidation. Genistein increases the activity of other antioxidant enzymes such as glutathione peroxidase, superoxide dismutase and glutathione reductase. Studies have shown that genistein can also influence the growth of cells which are not hormone-dependent. Anticancer Genistein seems to reduce the risk for some hormone related cancers, principally breast cancer and prostate cancer. Epidemiological studies show that consumption of isoflavones may protect against breast and prostate cancer. High dietary intake of soy products China and Japan are linked with low incidence of these cancers. There are lots of theories to explain the anti-cancer action of genistein: inhibition of angiogenesis, inhibition of tyrosine kinases, antioxidant property, and anti-estrogen action (it is known that estrogen increases risk for certain cancers). Genistein binds with estrogen receptors, preventing the estrogen from binding and initiating cancer growth. Heart health Many in-vitro tests have demonstrated that genistein inhibits cellular cholesterol synthesis and cholesterol esterification. Genistein also reduces fatty acid oxidation and exerts lipid lowering effect. Only oxidized LDL cholesterol is absorbed by the arterial cells and prevention of this oxidation will reduce the risk for arteriosclerosis. Gensistein prevents the formation of hearth attacks and strokes by acting as anticlotting agent. References http://www.phytochemicals.info/phytochemicals/genistein.php
Biological Activity
Phytoestrogen with a wide range of biological actions. Inhibits protein tyrosine kinases including epidermal growth factor receptor kinase. Also binds to PPAR γ and estrogen receptors and acts as an agonist at GPR30. Also available as part of the MAPK Cascade Inhibitor Tocriset? .
Biochem/physiol Actions
Inhibitor of tyrosine protein kinase; competitive inhibitor of ATP in other protein kinase reactions. Antiangiogenic agent, down-regulates the transcription of genes involved in controlling angiogenesis.
Anticancer Research
It is an isoflavone and is obtained from a variety of plants like psoralea (Psoraleacorylifolia), kudzu (Pueraria lobata), faba beans (Vicia faba), and soybeans(Glycine max). It exhibits anticancer effect by inhibiting NF-κB and protein kinaseB (Akt) signaling pathways (Singh et al. 2016b). It blocks the proliferation of cancercells via the inhibition of cell growth enzymes and survival like tyrosine kinase andtopoisomerase II; hence it is used to treat leukemia. Genistein increases the growthrate of some estrogen receptors in breast cancer cells and the rate of proliferation of estrogen-dependent breast cancer by competitive binding to the estrogen-β receptors.It may be involved in JNK pathway in inducing activator protein-1(AP-1) activity(Wang et al. 2012; Dixon and Ferreira 2002).
Safety Profile
Experimental
reproductive effects. Human mutation data
reported. When heated to decomposition it
emits acrid smoke and irritating fumes.
Purification Methods
Crystallise it from EtOH or aqueous EtOH. It has UV: max at 290nm (EtOH). The S(-)-enantiomer (natural form) has m 255-256o (from EtOH) and [] D 20 -28.0o (c 2, EtOH), [ ] D 20 -35.2o (c 1, pyridine).[Beilstein 18 H 503, 18 II 164, 18 III/IV 2630.] Genistein (4',5,7-trihydroxyisoflavone) [446-72-0]M 270.2 crystallises from 60% aqueous EtOH or water with m 297-298o and [] D 20 -28o (c 0.6, 20mM NaOH). [Beilstein 18/4 V 594.]For Naringin (naringenin 7-rhamnoglucoside) See “Carbohydrates” in Chapter 6.
References
1) Akiyama?et al.?(1987),?Genistein, a specific inhibitor of tyrosine-specific protein kinases; J. Biol. Chem.,?262?5592
2) Linassier?et al.?(1990),?Mechanisms of action in NIH-3T3 cells of genistein, an inhibitor if EGF receptor tyrosine kinase?Biochem. Pharmacol.,?39?187
3) Dang?et al.?(2003),?Peroxisome proliferator-activated receptor gamma (PPARgamma) as a molecular target for the soy phytoestrogen genistein; J. Biol. Chem.,?278?962
4) Vivacqua?et al.?(2006),?17beta-estradiol, genistein, and 4-hydroxytamoxifen induce the proliferation of thyroid cancer cells through the g protein-coupled receptor GPR30; Mol. Pharmacol., 70?1414
5) Sarker and Li (2002),?Mechanisms of cancer chemoprevention by soy isoflavone genistein; Cancer Metastasis Rev.,?21?265
Check Digit Verification of cas no
The CAS Registry Mumber 446-72-0 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 4,4 and 6 respectively; the second part has 2 digits, 7 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 446-72:
(5*4)+(4*4)+(3*6)+(2*7)+(1*2)=70
70 % 10 = 0
So 446-72-0 is a valid CAS Registry Number.
InChI: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
446-72-0Relevant articles and documents
Hydrolysis of soybean isoflavonoid glycosides by Dalbergia β-glucosidases
Chuankhayan, Phimonphan,Rimlumduan, Thipwarin,Svasti, Jisnuson,Ketudat Cairns, James R.
, p. 2407 - 2412 (2007)
Two β-glucosidases from the legumes Dalbergia cochinchinensis and Dalbergia nigrescens were compared for their ability to hydrolyze isoflavonoid glycosides from soybean. Both D. nigrescens and D. cochinchinensis β-glucosidases could hydrolyze conjugated soybean glycosides, but D. nigrescens β-glucosidase hydrolyzed both conjugated and nonconjugated glycosides in crude soybean extract more rapidly. The kinetic properties K m, kcat, and kcat/Km of the Dalbergia β-glucosidases toward conjugated isoflavonoid glycosides, determined using high-performance liquid chromatography, confirmed the higher efficiency of the D. nigrescens β-glucosidase in hydrolyzing these substrates. The D. nigrescens β-glucosidase could also efficiently hydrolyze isoflavone glycosides in soy flour suspensions, suggesting its application to increase free isoflavones in soy products.
Deglycosylation of isoflavonoid glycosides from maackia amurensis cell culture by β-D-glucosidase from littorina sitkana hepatopancrease
Kusaikin,Zakharenko,Ermakova,Veselova,Grigoruk,Fedoreev,Zvyagintseva
, p. 197 - 200 (2011)
Maakia amurensis (strain A-18) cell culture synthesizes a significant quantity of isoflavonoids, a large part of which consists of isoflavone glucosides and malonylglucosides. β-D-Hydrolase enzyme complexes from the marine mollusk Littorina sitkana and the marine mycelial fungus P. canescens were used to obtain isoflavones from their conjugated forms. The specificity of β-D-glucanases from L. sitkana for various glycosides was studied. The deglycosylation efficiency depended on the aglycon structure. The deglycosylated fraction of isoflavonoids obtained from M. amurensis cell culture exhibited antitumor activity.
Anti-inflammatory isoflavonoids from the stems of Derris scandens
Laupattarakasem, Pisamai,Houghton, Peter J.,Hoult, J. Robin S.
, p. 496 - 501 (2004)
Fractionation of the aqueous extract of Derris scandens stems extract using tests for eicosanoid inhibition resulted in the isolation of three isoflavonoids, genistein, its 7-O-α-rhamno(1→6)-β-glucosyl glycoside, a new compound, and two known isoprenyl derivatives 3′-γ,γ-dimethylallylweighteone and scandenin. The isoprenylated compounds showed a high inhibitory effect on eicosanoid production in vitro but HPLC analysis showed that the genistein accounted for most of the activity of the total extract. Antioxidant studies showed that genistein and the isoprenylated compounds showed activity comparable to standard antioxidants. Genistein and its glycoside demonstrated no cytotoxicity in the MTT test but the prenylated compounds showed some toxicity and also increased LDH release from polymorphonucleocytes, at concentrations much greater than would be encountered in an aqueous extract of D. scandens.
A novel method for the highly efficient biotransformation of genistein from genistin using a high-speed counter-current chromatography bioreactor
Wang, Daijie,Khan, Muhammad Shafiq,Cui, Li,Song, Xiangyun,Zhu, Heng,Ma, Tianyu,Li, Xiaoyu,Sun, Rong
, p. 4892 - 4899 (2019)
Genistein, an important soybean isoflavone compound, has gained attention for its significant properties. Compared with the glycone form of genistin, low content of genistein limits the use in food and pharmaceutical fields. In this study, a novel bioreactor with high-speed counter-current chromatography (HSccc) was built for the highly efficient biotransformation of genistein from genistin. The solvent system for the bioreactor was selected according to the KD values. The selected solvent system was evaluated by the enzyme activity of β-glucosidase. An ethyl acetate/buffer solution was selected as the preferred solvent system for the HSccc bioreactor. Optimum reactor parameters were selected according to the retention of the stationary phase. The HSccc bioreactor was operated using different flow rates, and 2.0 mL min-1 was chosen as the optimal flow rate with a conversion rate of over 90% within 24 h; the novel bioreactor easily immobilized and recycled the enzyme and could be applied in the preparation of genistein.
Chevalierinoside B and C: Two new isoflavonoid glycosides from the stem bark of Antidesma laciniatum Muell. Arg (syn. Antidesma chevalieri Beille)
Djouossi, Marie Geneviève,Mabou, Florence Déclaire,Foning Tebou, Perrin Lanversin,Ngnokam, David,Tapondjou, Leon A.,Harakat, Dominique,Voutquenne-Nazabadioko, Laurence
, p. 149 - 152 (2014)
Chevalierinosides B (1) and C (2), two new isoflavonoid glycosides, characterized as biochanin A 7-O-[β-d-apiofuranosyl-(1→2)-β-d- glucopyranoside] and genistein 7-O-[β-d-apiofuranosyl-(1→2)-β-d- glucopyranoside], together with the known isoflavonoids, chevalierinoside A (3) and genistein 7-O-β-d-glucopyranoside (4), kaempferol 3-O-β-d- glucopyranoside (5) and triterpenes, friedelin (6), betulinic acid (7), 30-oxobetulinic acid (8), 30-hydroxybetulinic acid (9), were isolated from the stem bark of Antidesma laciniatum Muell. Arg. (syn. Antidesma chevalieri Beille). Their structures were established by direct interpretation of their spectral data, mainly HR-TOFESIMS, 1D-NMR (1H, 13C and DEPT) and 2D-NMR (COSY, NOESY, TOCSY, HSQC and HMBC), and by comparison with the literature.
First finding of Daidzein 7-O-phosphate and Genistein 7-O-phosphate that are hydrolyzed by sulfatase
Kanakubo, Akira,Koga, Kazushi,Isobe, Minoru,Fushimi, Tatsushi,Saitoh, Takanobu,Ohshima, Yoshifumi,Tsukamoto, Yoshinori
, p. 8801 - 8805 (2001)
Attempted structural assignment of two water soluble isoflavone analogs of Daidzein and Genistein, was initially assumed to be the corresponding sulfates on the basis of the facts that these analogs were hydrolyzed by sulfatase; however, they were eventua
Identification of ortho catechol-containing isoflavone as a privileged scaffold that directly prevents the aggregation of both amyloid β plaques and tau-mediated neurofibrillary tangles and its in vivo evaluation
Do, Ji Min,Gee, Min Sung,Inn, Kyung-Soo,Kim, Jong-Ho,Kim, Nam Kwon,Kim, Nam-Jung,Lee, Hyun Woo,Lee, Jong Kil,Seo, Min-Duk,Seong, Ji Hye,Son, Seung Hwan,Yoo, Hyung-Seok,Yoo, Ji-Na
, (2021/07/01)
In this study, polyhydroxyisoflavones that directly prevent the aggregation of both amyloid β (Aβ) and tau were expediently synthesized via divergent Pd(0)-catalyzed Suzuki-Miyaura coupling and then biologically evaluated. By preliminary structure–activity relationship studies using thioflavin T (ThT) assays, an ortho-catechol containing isoflavone scaffold was proven to be crucial for preventing both Aβ aggregation and tau-mediated neurofibrillary tangle formation. Additional TEM experiment confirmed that ortho-catechol containing isoflavone 4d significantly prevented the aggregation of both Aβ and tau. To investigate the mode of action (MOA) of 4d, which possesses an ortho-catechol moiety, 1H-15N HSQC NMR analysis was thoroughly performed and the result indicated that 4d could directly inhibit both the formation of Aβ42 fibrils and the formation of tau-derived neurofibrils, probably through the catechol-mediated nucleation of tau. Finally, 4d was demonstrated to alleviate cognitive impairment and pathologies related to Alzheimer's disease in a 5XFAD transgenic mouse model.
Continuous flow microchannel synthesis process of flavonoid compounds
-
Paragraph 0050-0059; 0061, (2021/06/22)
The invention provides a continuous flow microchannel synthesis process of flavonoid compounds. According to the process, hesperidin and iodine elementary substance are used as raw materials and react in a continuous flow microchannel reactor in the presence of a reaction solvent to synthesize the flavonoid compound as shown in a formula A. Compared with a traditional kettle-type preparation process, the process disclosed by the invention has the advantages that the preparation time is obviously shortened, and the conversion rate of raw materials and the yield of products are obviously improved; and especially, when the diosmin is prepared under optimal process conditions of continuous flow microchannel synthesis, the conversion rate of the raw material hesperidin is as high as 96.48%, and the yield of the product diosmin is as high as 81.96%. The continuous flow micro-channel synthesis process provided by the invention is beneficial to realizing safe, efficient and rapid industrial production of flavonoid compounds, and has a wide application prospect.
Cytosine N-isoflavone compound as well as preparation method and application thereof
-
Paragraph 0029; 0037-0038, (2019/10/02)
The invention relates to a cytosine N-isoflavone compound as well as a preparation method and application thereof. The compound has a structural formula as shown in the specification, wherein R1 is selected from one of hydroxyl, alkoxy, amido or halo, R2 is selected from one of hydrogen, alkyl or aryl, and R3 is selected from one or a combination of several of hydroxyl, alkoxy, amido or halo. Compared with the prior art, the cytosine N-isoflavone compound has the characteristic that an isoflavone compound serving as a structural unit is spliced to N on the 12th position of cytosine by using acombined synthesis technology, so that a series of cytosine-isoflavone derivatives are synthesized, and a novel active pharmacological action is exerted.
Synthesis, Characterization, and Antioxidant Activities of Genistein, Biochanin A, and Their Analogues
Hamza Sherif, Salah,Gebreyohannes, BerihuTekluu
, (2018/04/30)
A series of naturally occurring genistein (3) and biochanin A (4) compounds and their analogues were synthesized from phloroglucinol. The structures of all the synthesized compounds were established by the combined use of 1HNMR, 13CNMR, IR spectral data, and mass spectrometry; their antioxidant activities were investigated. Most of the synthesized compounds show moderate-to-high activity; only two compounds exhibit no significant activity.
