Biochanin A
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Basic Info
| Common Name | Biochanin A(F05582) |
| 2D Structure | |
| Description | The phytoestrogen biochanin A is an isoflavone derivative isolated from red clover Trifolium pratense with anticarcinogenic properties. Treating MCF-7 human breast carcinoma cells with biochanin A alone caused the accumulation of CYP1A1 mRNA and an increase in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. Biochanin A may be a natural ligand to bind on aryl hydrocarbon receptor acting as an antagonist/agonist of the pathway. (A7920). Biochanin A suppress nuclear factor-kappaB-driven interleukin-6 (IL6) expression. In addition to its physiologic immune function as an acute stress cytokine, sustained elevated expression levels of IL6 promote chronic inflammatory disorders, aging frailty, and tumorigenesis. (A7921). Biochanin A induces a decrease in invasive activity of U87MG cells in a dose-related manner. (A7922). Biochanin A activates peroxisome proliferator-activated receptors (PPAR) PPARalpha, PPARgamma, and adipocyte differentiation in vitro of 3T3-L1 preadipocytes, suggesting potential value of isoflavones, especially biochanin A and their parent botanicals, as antidiabetic agents and for use in regulating lipid metabolism. (A7923). |
| FRCD ID | F05582 |
| CAS Number | 491-80-5 |
| PubChem CID | 5280373 |
| Formula | C16H12O5 |
| IUPAC Name | 5,7-dihydroxy-3-(4-methoxyphenyl)chromen-4-one |
| InChI Key | WUADCCWRTIWANL-UHFFFAOYSA-N |
| InChI | InChI=1S/C16H12O5/c1-20-11-4-2-9(3-5-11)12-8-21-14-7-10(17)6-13(18)15(14)16(12)19/h2-8,17-18H,1H3 |
| Canonical SMILES | COC1=CC=C(C=C1)C2=COC3=CC(=CC(=C3C2=O)O)O |
| Isomeric SMILES | COC1=CC=C(C=C1)C2=COC3=CC(=CC(=C3C2=O)O)O |
| Synonyms |
biochanin A
491-80-5
Biochanin
4'-Methylgenistein
5,7-Dihydroxy-4'-methoxyisoflavone
5,7-Dihydroxy-3-(4-methoxyphenyl)-4H-chromen-4-one
Genistein 4-methyl ether
Pratensol
Biochanine A
4H-1-Benzopyran-4-one, 5,7-dihydroxy-3-(4-methoxyphenyl)-
|
| Classifies |
Plant Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Phenylpropanoids and polyketides |
| Class | Isoflavonoids |
| Subclass | O-methylated isoflavonoids |
| Intermediate Tree Nodes | 4'-O-methylated isoflavonoids |
| Direct Parent | 4'-O-methylisoflavones |
| Alternative Parents |
|
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | 4p-o-methylisoflavone - Isoflavone - Hydroxyisoflavonoid - Chromone - Benzopyran - 1-benzopyran - Anisole - Phenoxy compound - Phenol ether - Methoxybenzene - 1-hydroxy-4-unsubstituted benzenoid - 1-hydroxy-2-unsubstituted benzenoid - Pyranone - Alkyl aryl ether - Monocyclic benzene moiety - Benzenoid - Pyran - Vinylogous acid - Heteroaromatic compound - Ether - Organoheterocyclic compound - Oxacycle - Organooxygen compound - Organic oxygen compound - Hydrocarbon derivative - Organic oxide - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as 4'-o-methylisoflavones. These are isoflavones with methoxy groups attached to the C4' atom of the isoflavone backbone. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 284.267 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 2 |
| Complexity | 424 |
| Monoisotopic Mass | 284.068 |
| Exact Mass | 284.068 |
| XLogP | 3 |
| Formal Charge | 0 |
| Heavy Atom Count | 21 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB- | 0.5674 |
| Human Intestinal Absorption | HIA+ | 0.9816 |
| Caco-2 Permeability | Caco2+ | 0.9526 |
| P-glycoprotein Substrate | Substrate | 0.6232 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.8111 |
| Inhibitor | 0.6095 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8889 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.7877 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7181 |
| CYP450 2D6 Substrate | Non-substrate | 0.8957 |
| CYP450 3A4 Substrate | Non-substrate | 0.6019 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.9540 |
| CYP450 2C9 Inhibitor | Inhibitor | 0.8287 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.6939 |
| CYP450 2C19 Inhibitor | Inhibitor | 0.9470 |
| CYP450 3A4 Inhibitor | Inhibitor | 0.7746 |
| CYP Inhibitory Promiscuity | High CYP Inhibitory Promiscuity | 0.8845 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9521 |
| Non-inhibitor | 0.8682 | |
| AMES Toxicity | Non AMES toxic | 0.9132 |
| Carcinogens | Non-carcinogens | 0.9347 |
| Fish Toxicity | High FHMT | 0.8680 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9965 |
| Honey Bee Toxicity | High HBT | 0.7212 |
| Biodegradation | Not ready biodegradable | 0.8757 |
| Acute Oral Toxicity | III | 0.7005 |
| Carcinogenicity (Three-class) | Non-required | 0.6169 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.1911 | LogS |
| Caco-2 Permeability | 1.0841 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.8328 | LD50, mol/kg |
| Fish Toxicity | 0.4944 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 1.4646 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Main Isoflavones Found in Dietary Sources as Natural Anti-inflammatory Agents. | Curr Drug Targets | 2018 | 29141545 |
| Aluminum-induced molecular neurodegeneration: The protective role of genisteinand chickpea extract. | Food Chem Toxicol | 2017 Sep | 28552514 |
| Neurochemical and Behavior Deficits in Rats with Iron and Rotenone Co-treatment: Role of Redox Imbalance and Neuroprotection by Biochanin A. | Front Neurosci | 2017 Nov 23 | 29217997 |
| Multiresidue determination of estrogens in different dairy products by ultra-high-performance liquid chromatography triple quadrupole mass spectrometry. | J Chromatogr A | 2017 May 5 | 28363417 |
| Phytoestrogens in milk: Overestimations caused by contamination of the hydrolytic enzyme used during sample extraction. | J Dairy Sci | 2016 Sep | 27394955 |
| Biochanin A improves hepatic steatosis and insulin resistance by regulating thehepatic lipid and glucose metabolic pathways in diet-induced obese mice. | Mol Nutr Food Res | 2016 Sep | 27145114 |
| Biochanin A Protects Against Lipopolysaccharide-Induced Damage of Dopaminergic Neurons Both In Vivo and In Vitro via Inhibition of Microglial Activation. | Neurotox Res | 2016 Oct | 27417698 |
| Natural product HTP screening for antibacterial (E.coli 0157:H7) and anti-inflammatory agents in (LPS from E. coli O111:B4) activated macrophages and microglial cells; focus on sepsis. | BMC Complement Altern Med | 2016 Nov 15 | 27846826 |
| Biochanin A protects dopaminergic neurons against lipopolysaccharide-induced damage and oxidative stress in a rat model of Parkinson's disease. | Pharmacol Biochem Behav | 2015 Nov | 26394281 |
| Isoflavones in food supplements: chemical profile, label accordance andpermeability study in Caco-2 cells. | Food Funct | 2015 Mar | 25653232 |
| Thermal stability of kudzu root (Pueraria Radix) isoflavones as additives to beefpatties. | J Food Sci Technol | 2015 Mar | 25745227 |
| Biochanin A attenuates LPS-induced pro-inflammatory responses and inhibits the activation of the MAPK pathway in BV2 microglial cells. | Int J Mol Med | 2015 Feb | 25483920 |
| Cellular DNA breakage by soy isoflavone genistein and its methylated structuralanalogue biochanin A. | Mol Nutr Food Res | 2009 Nov | 19743405 |
| Biochanin A protects dopaminergic neurons against lipopolysaccharide-induced damage through inhibition of microglia activation and proinflammatory factors generation. | Neurosci Lett | 2007 May 1 | 17399896 |
| Differential modulation of ochratoxin A absorption across Caco-2 cells by dietary polyphenols, used at realistic intestinal concentrations. | Toxicol Lett | 2005 Oct 15 | 15955639 |
| Suppression of arachidonic acid metabolism and nitric oxide formation by kudzu isoflavones in murine macrophages. | Mol Nutr Food Res | 2005 Dec | 16254887 |
| Phytoestrogens derived from red clover: an alternative to estrogen replacementtherapy? | J Steroid Biochem Mol Biol | 2005 Apr | 15876415 |
| Determination of unusual soya and non-soya phytoestrogen sources in beer, fishproducts and other foods. | Food Addit Contam | 2004 Oct | 15712520 |
| Combined effects of multiple flavonoids on breast cancer resistance protein(ABCG2)-mediated transport. | Pharm Res | 2004 Jul | 15290869 |
| Phytoestrogens possess a weak antioxidant activity on low density lipoprotein in contrast to the flavonoid quercetin in vitro in postmenopausal women. | Climacteric | 2004 Dec | 15799611 |
Targets
- General Function:
- Zinc ion binding
- Specific Function:
- Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism. Induces the expression of PERM1 in the skeletal muscle.
- Gene Name:
- ESRRA
- Uniprot ID:
- P11474
- Molecular Weight:
- 45509.11 Da
References
- Suetsugi M, Su L, Karlsberg K, Yuan YC, Chen S: Flavone and isoflavone phytoestrogens are agonists of estrogen-related receptors. Mol Cancer Res. 2003 Nov;1(13):981-91. [14638870 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.
- Gene Name:
- NR1H4
- Uniprot ID:
- Q96RI1
- Molecular Weight:
- 55913.915 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
- Gene Name:
- ESR2
- Uniprot ID:
- Q92731
- Molecular Weight:
- 59215.765 Da
References
- Overk CR, Yao P, Chadwick LR, Nikolic D, Sun Y, Cuendet MA, Deng Y, Hedayat AS, Pauli GF, Farnsworth NR, van Breemen RB, Bolton JL: Comparison of the in vitro estrogenic activities of compounds from hops (Humulus lupulus) and red clover (Trifolium pratense). J Agric Food Chem. 2005 Aug 10;53(16):6246-53. [16076101 ]
- General Function:
- Oxygen binding
- Specific Function:
- Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
- Gene Name:
- CYP19A1
- Uniprot ID:
- P11511
- Molecular Weight:
- 57882.48 Da
References
- Kao YC, Zhou C, Sherman M, Laughton CA, Chen S: Molecular basis of the inhibition of human aromatase (estrogen synthetase) by flavone and isoflavone phytoestrogens: A site-directed mutagenesis study. Environ Health Perspect. 1998 Feb;106(2):85-92. [9435150 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
- Gene Name:
- AR
- Uniprot ID:
- P10275
- Molecular Weight:
- 98987.9 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Atp binding
- Specific Function:
- Involved in DNA damage response. Involved in a RAD9A-related damage checkpoint, a pathway that is important in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis. Modulates the RAD9A interaction with BCL2 and thereby induces DNA damages-induced apoptosis.
- Gene Name:
- ATAD5
- Uniprot ID:
- Q96QE3
- Molecular Weight:
- 207568.185 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2.
- Gene Name:
- PPARA
- Uniprot ID:
- Q07869
- Molecular Weight:
- 52224.595 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Zinc ion binding
- Specific Function:
- The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
- Gene Name:
- PGR
- Uniprot ID:
- P06401
- Molecular Weight:
- 98979.96 Da
References
- Scippo ML, Argiris C, Van De Weerdt C, Muller M, Willemsen P, Martial J, Maghuin-Rogister G: Recombinant human estrogen, androgen and progesterone receptors for detection of potential endocrine disruptors. Anal Bioanal Chem. 2004 Feb;378(3):664-9. Epub 2003 Oct 25. [14579009 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear receptor, may regulate ESR1 transcriptional activity. Induces the expression of PERM1 in the skeletal muscle.
- Gene Name:
- ESRRB
- Uniprot ID:
- O95718
- Molecular Weight:
- 56207.085 Da
References
- Suetsugi M, Su L, Karlsberg K, Yuan YC, Chen S: Flavone and isoflavone phytoestrogens are agonists of estrogen-related receptors. Mol Cancer Res. 2003 Nov;1(13):981-91. [14638870 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
- Gene Name:
- ESR1
- Uniprot ID:
- P03372
- Molecular Weight:
- 66215.45 Da
References
- Overk CR, Yao P, Chadwick LR, Nikolic D, Sun Y, Cuendet MA, Deng Y, Hedayat AS, Pauli GF, Farnsworth NR, van Breemen RB, Bolton JL: Comparison of the in vitro estrogenic activities of compounds from hops (Humulus lupulus) and red clover (Trifolium pratense). J Agric Food Chem. 2005 Aug 10;53(16):6246-53. [16076101 ]
- General Function:
- Cholesterol binding
- Specific Function:
- Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1847678).
- Gene Name:
- TSPO
- Uniprot ID:
- P30536
- Molecular Weight:
- 18827.81 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
- General Function:
- Transcription regulatory region dna binding
- Specific Function:
- Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
- Gene Name:
- AHR
- Uniprot ID:
- P35869
- Molecular Weight:
- 96146.705 Da
References
- Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]