485-72-3

Basic information

• Product Name: Formononetin
• Synonyms: 7-Hydroxy-3-(4-methoxyphenyl)chromone, 7-Hydroxy-4μ-methoxyisoflavone;Formononetin，Formoononetin;4H-1-Benzopyran-4-one, 7-hydroxy-3-(4-methoxyphenyl)-;Daidzein 4'-methyl ether;Formononetin ,98%;4'-Methoxy-7-hydroxyisoflavone;7-Hydroxy-3-(4-methoxyphenyl)-4H-1-benzopyran-4-one;Formononetin,99%
• CAS NO: 485-72-3
• Molecular Formula: C₁₆H₁₂O₄
• Molecular Weight: 268.27
• EINECS: 207-623-9
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;natural product;Iso-Flavones;The group of Astralosides;Inhibitors
• Mol File: 485-72-3.mol

Chemical Properties

• Melting Point: 256-260 °C
• Boiling Point: 331.43°C (rough estimate)
• Flash Point: 183.4 °C
• Appearance: White to light beige/Powder
• Density: 1.1529 (rough estimate)
• Vapor Pressure: 8.17E-10mmHg at 25°C
• Refractive Index: 1.4350 (estimate)
• Storage Temp.: Refrigerator
• Solubility: Soluble in DMSO (up to 100 mg/ml).
• PKA: 6.99±0.20(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month.
• Merck: 14,4244
• BRN: 237979
• CAS DataBase Reference: Formononetin(CAS DataBase Reference)
• NIST Chemistry Reference: Formononetin(485-72-3)
• EPA Substance Registry System: Formononetin(485-72-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 37/39-26-36
• WGK Germany: 3
• RTECS: DJ3100114
• Hazardous Substances Data: 485-72-3(Hazardous Substances Data)

Usage

Chemical Properties

off-white powder

Uses

Different sources of media describe the Uses of 485-72-3 differently. You can refer to the following data:
1. An isoflavone found in a variety of plants. When metabolized in the rumen this compound transforms into a potent estrogen.
2. Formononetin is an isoflavone found as one of the main plant estrogens in animal feed. When metabolized in the rumen this compound transforms into a potent estrogen.
3. phytoestrogen
4. Formononetin is an isoflavonoid phytoestrogenic compound found in soy-based foods and is the precursor of daidzein . It acts as an agonist of the aryl hydrocarbon receptor with an EC50 value of 0.13 μM. Formononetin has been reported to possess antitumor and antiviral activity.

General Description

Formononetin belongs to the isoflavones class of polyphenols.

Flammability and Explosibility

Notclassified

Biochem/physiol Actions

Isoflavone found in red clover. Effective against Giardia lamblia infection, at least partially by inducing detachment of trophozoites from intestinal mucosa.

References

1) Nie?et al.?(2018),?The natural compound, formononetin, extracted from Astragalus membranaceus increases adipocyte thermogenesis by modulating PPARγ activity; Br. J. Pharmacol.,?175?1439 2) Gautam?et al.?(2017),?Formononetin, an isoflavone, activates AMO-activated protein kinase/?β-catenin signaling to inhibit adipogenesis and rescues C57BL/6 mice from high-fat diet-induced obesity and bone loss; Br. J. Nutrit.,?117?645 3) Huh?et al. (2011),?Formononetin accelerates wound repair by the regulation of early growth response factor-1 transcription factor through the phosphorylation of the ERK and p38 MAPK pathways; Int. Immunopharmacol.,?11?46 4) Ong?et al.?(2019),?Focus on Formononetin: Anticancer Potential and Molecular Targets; Cancers (Basel),?11?E611 5) Li?et al.?(2018),?Neuroprotective effect of formononetin against TBI in rats via suppressing inflammatory reaction in cortical neurons; Biomed. Pharmacother.,?106?349

InChI:InChI=1/C16H12O4/c1-19-12-5-2-10(3-6-12)14-9-20-15-8-11(17)4-7-13(15)16(14)18/h2-9,17H,1H3

Upstream product

• 853925-87-8 7-hydroxy-3-(4-methoxyphenyl)-4-oxo-4H-chromene-2-carboxylic acid 
• 487-49-0 1-(2,4-dihydroxyphenyl)-2-(4-methoxyphenyl)ethanone 
• 122-51-0 orthoformic acid triethyl ester 
• 486-62-4 ononin 
• 109-94-4 formic acid ethyl ester 
• 186581-53-3 diazomethane 
• 486-66-8 daidzein 
• 290-87-9 1,3,5-Triazine 
• 2258-42-6 formyl acetic anhydride 
• 4637-24-5 N,N-dimethyl-formamide dimethyl acetal 
• 68-12-2 N,N-dimethyl-formamide 
• 485-80-3 S-adenosyl-L-methionine 
• 109963-62-4 2,7,4'-trihydroxyisoflavanone 
• 69097-97-8 7,4'-dihydroxy-dihydroflavone 

Downstream Products

• 853927-76-1 7-hydroxy-3-(4-methoxyphenyl)-4-oxo-4H-1-benzopyran-8-carboxaldehyde 
• 13293-49-7 3-(4-methoxyphenyl)-4-oxo-4H-chromene-7-yl acetate 
• 76260-67-8 7-ethoxy-3-(4-methoxyphenyl)-4H-chromen-4-one 
• 487-49-0 1-(2,4-dihydroxyphenyl)-2-(4-methoxyphenyl)ethanone 
• 10499-17-9 3,4-dihydro-7-hydroxy-3-(4-methoxyphenyl)-2H-1-benzopyran 
• 42868-84-8 formononetin tetra-O-acetyl-β-D-glucopyranoside 
• 57203-25-5 2,4-dimethyl-7-hydroxy-4'-methoxyisoflavene 
• 110560-94-6 2,4-diethyl-7-hydroxy-4'-methoxyisoflavene 
• 4267-37-2 4'-methoxy-7-trimethylsilyloxyisoflavone 
• 4626-22-6 Dihydroformononetin 
• 124093-20-5 trans-7-hydroxy-4'-methoxyisoflavan-4-ol 
• 64474-51-7 (3R)-7,2'-dihydroxy-3',4'-dimethoxyisoflaven 
• 642-39-7 angolensin 
• 64-18-6 formic acid 

Relevant articles and documents

Metabolic studies of four soy isoflavones in rats by HPLC-HR-MS

In this paper, the metabolites of four soy isoflavones, daidzein, daidzin, genistein, and genistin, on perfused rat intestine-liver model were investigated by high-performance liquid chromatography coupled with high-resolution mass spectrometer/tandem mass spectrometer. Totally 16 metabolites were detected and identified based on accurate mass, fragmentation patterns, and multiple-stage mass data (MSn). The metabolic site of dadzein-7-methyl ether (D-7-M) was further confirmed by nuclear magnetic resonance. Methylation, glucuronide conjugation, and sulfate conjugation were the primary metabolic processes. Among them, six metabolites, daidzin-4′,7-diglucoside, genistein-4′- glucoside, D-7-M, dadzein-4′,7-dimethyl ether, genistein-4′-methyl ether, and genistein-7-methyl ether were detected in rats for the first time and not reported in humans. The metabolic pathways of daidzein, daidzin genistein, and genistin in rats were postulated. The biological effects of these metabolites are worthy of further investigation.

New scheme of the biosynthesis of formononetin involving 2,7,4′-trihydroxyisoflavanone but not daidzein as the methyl acceptor

Glycyrrhiza echinata cell-free extract produced isoformononetin by the 7-O-transmethylation of daidzein from S-adenosyl-L-methionine (SAM). When the yeast microsome expressing 2-hydroxyisoflavanone synthase was mixed with the cell-free extract and incubated with liquiritigenin and SAM, formononetin emerged. Furthermore, the cell-free extract yielded formononetin on incubation with 2,7,4′-trihydroxyisoflavanone and SAM. We propose a novel pathway of formononetin biosynthesis involving 2,7,4′-trihydroxyisoflavanone as the methyl acceptor.

INDUCIBLY-FORMED ISOFLAVONOIDS FROM LEAVES OF SOYBEAN

Isoformononetin, glyceollins I, II and III, and 2-isopentenyl-3,6α,9-trihydroxypterocarpan (glyceocarpin) accumulated in soybean (Glycine max) leaves after treatment with aqueous sodium iodoacetate or a cell suspension of the bacterium, Pseudomonas pisi.These compounds were also accompanied by two previously unreported pterocarpans, glycerofuran and its 9-O-methyl derivative.Glyceocarpin is described for the first time as a plant product.Key Word Index- Glycine max; Leguminosae; soybean; Pseudomonas pisi; isoflavonoids; pterocarpans; isoflavone; phytoalexins; antibacterial activity.

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

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.

Scope and Applications of 2,3-Oxidative Aryl Rearrangements for the Synthesis of Isoflavone Natural Products

The reaction of flavanones with hypervalent iodine reagents was investigated with a view to the synthesis of naturally occurring isoflavones. In contrast to several previous reports in the literature, we did not observe the formation of any benzofurans via a ring contraction pathway, but could isolate only isoflavones, resulting from an oxidative 2,3-aryl rearrangement, and flavones, resulting from an oxidation of the flavanones. Although the 2,3-oxidative rearrangement allows a synthetically useful approach toward some isoflavone natural products due to the convenient accessibility of the required starting materials, the overall synthetic utility and generality of the reaction appear to be more limited than previous literature reports suggest.

Structure-guided design and synthesis of isoflavone analogs of GW4064 with potent lipid accumulation inhibitory activities

Our group has previously reported a series of isoflavone derivatives with antidyslipidemic activity. With this background, a series of isoflavone analogs of GW4064 were designed, synthesized and evaluated the lipid-lowering activity of analogs. As a result, most of compounds significantly reduced the lipid accumulation in 3T3-L1 adipocytes and four of them (10a, 11, 15c and 15d) showed stronger inhibitory than GW4064. The most potent compound 15d exhibited promising agonistic activity for FXR in a cell-based luciferase reporter assay. Meanwhile, 15d up-regulated FXR, SHP and BSEP gene expression and down-regulated the mRNA expression of lipogenesis gene SREBP-1c. Besides, an improved safety profile of 15d was also observed in a HepG2 cytotoxicity assay compared with GW4064. The obtained biological results were further confirmed by a molecular docking study showing that 15d fitted well in the binding pocket of FXR and interacted with some key residues simultaneously.

Novel isoflavone derivative, preparation method therefor and medicinal use of novel isoflavone derivative

The invention relates to the field of pharmaceutical chemistry, relates to an isoflavone derivative, a preparation method therefor and medicinal use of the novel isoflavone derivative and particularlyrelates to isoflavone derivatives represented by a general formula (I) shown in the description, preparation methods therefor, pharmaceutical compositions containing these compounds and medicinal useof the isoflavone derivatives and the pharmaceutical compositions, particularly use of drugs for preventing or treating hyperlipidemia, type II diabetes, atherosclerosis and non-alcoholic fatty hepatitis.

CYTISINE-LINKED ISOFLAVONOID ANTINEOPLASTIC AGENTS FOR THE TREATMENT OF CANCER

Cytisine-linked isoflavonoids, or pharmaceutically acceptable salts thereof or pharmaceutically acceptable compositions thereof, are useful for the treatment of conditions in which cells have a reliance on peroxisomal HSD17B4 to degrade very long chain fatty acids and provide necessary energy for cell proliferation, such as is seen in colorectal cancer and prostate cancer, for example.

Developing antineoplastic agents that target peroxisomal enzymes: Cytisine-linked isoflavonoids as inhibitors of hydroxysteroid 17-beta-dehydrogenase-4 (HSD17B4)

Cytisine-linked isoflavonoids (CLIFs) inhibited PC-3 prostate and LS174T colon cancer cell proliferation by inhibiting a peroxisomal bifunctional enzyme. A pull-down assay using a biologically active, biotin-modified CLIF identified the target of these agents as the bifunctional peroxisomal enzyme, hydroxysteroid 17β-dehydrogenase-4 (HSD17B4). Additional studies with truncated versions of HSD17B4 established that CLIFs specifically bind the C-terminus of HSD17B4 and selectively inhibited the enoyl CoA hydratase but not the d-3-hydroxyacyl CoA dehydrogenase activity. HSD17B4 was overexpressed in prostate and colon cancer tissues, knocking down HSD17B4 inhibited cancer cell proliferation, suggesting that HSD17B4 is a potential biomarker and drug target and that CLIFs are potential probes or therapeutic agents for these cancers.

Repurposing Hsp90 inhibitors as antibiotics targeting histidine kinases

To address the growing need for new antimicrobial agents, we explored whether inhibition of bacterial signaling machinery could inhibit bacterial growth. Because bacteria rely on two-component signaling systems to respond to environmental changes, and because these systems are both highly conserved and mediated by histidine kinases, inhibiting histidine kinases may provide broad spectrum antimicrobial activity. The histidine kinase ATP binding domain is conserved with the ATPase domain of eukaryotic Hsp90 molecular chaperones. To find a chemical scaffold for compounds that target histidine kinases, we leveraged this conservation. We screened ATP competitive Hsp90 inhibitors against CckA, an essential histidine kinase in Caulobacter crescentus that controls cell growth, and showed that the diaryl pyrazole is a promising scaffold for histidine kinase inhibition. We synthesized a panel of derivatives and found that they inhibit the histidine kinases C. crescentus CckA and Salmonella PhoQ but not C. crescentus DivJ; and they inhibit bacterial growth in both Gram-negative and Gram-positive bacterial strains.