Equol [(-)-Equol, (3S)-Equol, (S)-Equol, AUS 131] is an isoflavandiol estrogen metabolized from daidzein, specifically, it is produced by intestinal bacteria in response to soy isoflavone intake in human. Equol is a metabolite of soybeans and is an important isoflavone that shows a wide range of activities including antioxidant activity, anti-inflammation activity and anticancer activity. It is reported that Equol specifically binds to 5α-DHT and has a modest affinity for recombinant estrogen receptor ERβ, which may be responsible for most of Equol's biological properties.
Physicochemical Properties
| Molecular Formula | C15H14O3 | |
| Molecular Weight | 242.27 | |
| Exact Mass | 242.094 | |
| Elemental Analysis | C, 74.36; H, 5.82; O, 19.81 | |
| CAS # | 531-95-3 | |
| Related CAS # | (±)-Equol;94105-90-5;(R)-Equol;221054-79-1 | |
| PubChem CID | 91469 | |
| Appearance | White to yellow solid | |
| Density | 1.3±0.1 g/cm3 | |
| Boiling Point | 441.7±45.0 °C at 760 mmHg | |
| Melting Point | 189-190ºC | |
| Flash Point | 220.9±28.7 °C | |
| Vapour Pressure | 0.0±1.1 mmHg at 25°C | |
| Index of Refraction | 1.645 | |
| Source | Endogenous Metabolite | |
| LogP | 2.98 | |
| Hydrogen Bond Donor Count | 2 | |
| Hydrogen Bond Acceptor Count | 3 | |
| Rotatable Bond Count | 1 | |
| Heavy Atom Count | 18 | |
| Complexity | 273 | |
| Defined Atom Stereocenter Count | 1 | |
| SMILES | O1C2C([H])=C(C([H])=C([H])C=2C([H])([H])[C@@]([H])(C2C([H])=C([H])C(=C([H])C=2[H])O[H])C1([H])[H])O[H] |
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| InChi Key | ADFCQWZHKCXPAJ-GFCCVEGCSA-N | |
| InChi Code | 1S/C15H14O3/c16-13-4-1-10(2-5-13)12-7-11-3-6-14(17)8-15(11)18-9-12/h1-6,8,12,16-17H,7,9H2/t12-/m1/s1 | |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | ER/estrogen receptor β (Ki = 0.73 nM) |
| ln Vitro | (-)-(S)-Equol has the highest affinity for ERβ (Ki=0.73±0.2 nM), although its affinity for ERα is rather poor (Ki=6.41±1 nM) [1]. (-)-(S)-Equol suppresses the proliferation of the LnCaP, DU145, and PC3 human prostate cancer cell lines. (-)-(S)-Equol causes cell cycle arrest in G2 in PC3 cells by downregulating cyclin B1 and CDK1 and upregulating CDK inhibitors (p21 and p27), as well as apoptosis by upregulating Fas ligand (FasL). /M phase) and production of pro-apoptotic Bim. (-)-(S)-Equol promotes FOXO3a expression, inhibits p-FOXO3a expression, and improves FOXO3a nuclear stability. (-)-(S)-Equol also lowers the expression of MDM2, which acts as an E3 ubiquitin ligase for p-FOXO3a, preventing p-FOXO3a from being destroyed by the proteasome. [2]. (-)-(S)-Equol enantioselectively promotes INS-1 cell viability, potentially by activating PKA signaling. (-)-(S)-Equol may be useful as an anti-type 2 diabetes medication. In INS-1 pancreatic beta cells, (-)-(S)-Equol phosphorylates cAMP response element-binding protein Ser 133 and promotes cAMP response element-mediated transcription [3]. |
| ln Vivo |
(-)-(S)-Equol demonstrated no overt toxicity on day 33, as evidenced by its ability to inhibit tumor growth by 43.2% and 28.4% when compared to the control [2]. Moreover, treatment with S-equol inhibited the growth of PC3 xenograft tumors in BALB/c nude mice. [2] |
| Enzyme Assay | With the use of chiral-phase HPLC and mass spectrometry, equol was isolated from human urine and plasma, and its enantiomeric structure was defined. Human fecal flora were cultured in vitro and incubated with daidzein to ascertain the stereospecificity of the bacterial production of equol. The pharmacokinetics of S- and R- equol were determined in 3 healthy adults after single-bolus oral administration of both enantiomers, and the affinity of each equol enantiomer for estrogen receptors was measured [1]. |
| Cell Assay | PC3 cells are seeded in 96-well culture plates (about 5×103 cells/ well) and cultured overnight at 37°C. Next, the cells are incubated with medium containing the indicated concentrations of (-)-(S)-Equol and/or DMSO for 72hr at 37°C. The cell viability is determined by the MTT assay [2]. |
| Animal Protocol | Mice are randomly divided into three groups of six mice each, and are treated by intragastric administration. The experimental groups are treated with 10 mg/kg or 20 mg/kg bodyweight of (-)-(S)-Equol (mice are treated everyday for 33 days). The control group is treated with an identical volume of 0.01ml sesame seed oil and 0.09 mL normal saline. The tumor size is examined every three days [2]. |
| Toxicity/Toxicokinetics | No indication of carcinogenicity to humans (not listed by IARC). |
| References |
[1]. S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora. Am J Clin Nutr. 2005 May;81(5):1072-9. [2]. S-equol, a Secondary Metabolite of Natural Anticancer Isoflavone Daidzein, Inhibits Prostate Cancer Growth In Vitro and In Vivo, Though Activating the Akt/FOXO3a Pathway. Curr Cancer Drug Targets. 2016;16(5):455-65. [3]. S-equol nantioselectively activates cAMP-protein kinase A signaling and reduces alloxan-induced cell death in INS-1 pancreatic β-cells. J Nutr Sci Vitaminol (Tokyo). 2014;60(4):291-6. |
| Additional Infomation |
Equol is a member of hydroxyisoflavans. Equol has been used in trials studying the treatment of Breast Cancer. Equol has been reported in Punica granatum with data available. S-equol is an orally bioavailable, non-steroidal estrogen naturally produced by the metabolism of the isoflavonoid daidzein by human intestinal microflora, with potential chemoprotective and estrogen receptor (ER) modulating activities. S-equol preferentially binds to and activates the beta isoform of ER in certain target tissues, while having an antagonistic effect in other tissues. This modulates the expression of ER-responsive genes in a tissue-specific manner. This agent may increase bone mineral density, affect vasomotor symptoms, and may decrease the proliferation rate of susceptible cancer cells. In addition, this agent interferes with the activity of enzymes involved in steroid biosynthesis. S-equol inhibits dihydrotestosterone (DHT) production and may inhibit the proliferation of androgen-driven prostate cancer. S-equol is the biologically active enantiomer while R-equol is essentially inactive and has a weak affinity for alpha-ER. Equol is a metabolite of daidzein, a phytoestrogen common in the human diet and abundant in soy. Intestinal bacteria in humans can reduce daidzein to equol, and can be found in normal human urine. The clinical effectiveness of soy isoflavones may be a function of the ability to biotransform soy isoflavones to the more potent estrogenic metabolite, equol, which may enhance the actions of soy isoflavones, owing to its greater affinity for estrogen receptors, unique antiandrogenic properties, and superior antioxidant activity. However, not all individuals consuming daidzein produce equol. Only approximately one-third to one-half of the population is able to metabolize daidzein to equol. This high variability in equol production is presumably attributable to interindividual differences in the composition of the intestinal microflora, which may play an important role in the mechanisms of action of isoflavones. (A3188, A3189). A non-steroidal ESTROGEN generated when soybean products are metabolized by certain bacteria in the intestines. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (10.32 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.32 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (10.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 10 mg/mL (41.28 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.1276 mL | 20.6381 mL | 41.2763 mL | |
| 5 mM | 0.8255 mL | 4.1276 mL | 8.2553 mL | |
| 10 mM | 0.4128 mL | 2.0638 mL | 4.1276 mL |