Product name: 7-Hydroxyflavanone
Synonym name:
Catalogue No.: BP4558
Cas No.: 6515-36-2
Formula: C₁₅H₁₂O₃
Mol Weight: 240.258
Botanical Source:
Type of Compound: Flavonoids

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.

For Reference Standard and R&D, Not for Human Use Directly.

HPLC of 7-Hydroxyflavanone

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Aromatase (CYP19) is a key rate limiting enzyme that catalyzes the conversion of androgen into estrogen in vivo. Its abnormal activity is closely related to the occurrence and development of estrogen dependent tumors such as breast cancer and endometrial cancer. Therefore, finding efficient and low toxicity aromatase inhibitors has become an important strategy for the development of anti estrogen therapeutic drugs. Among the candidate molecules from various natural product sources, 7-Hydroxyflavanone (CAS: 6515-36-2) has attracted much attention due to its specific inhibitory activity against aromatase (IC50=65 μ M). As a typical flavanone compound, 7-hydroxyflavanone not only exhibits direct anti estrogenic effects, but its pharmacological activity spectrum also covers multiple dimensions such as anti-cancer, antioxidant, and anti-inflammatory, indicating its potential for multi-target and multi pathway regulation of hormone homeostasis and intervention in related diseases. In recent years, with the in-depth exploration of its mechanism of action, especially its regulatory role in inflammation related signaling pathways, the research value of 7-hydroxyflavanone has surpassed single aromatase inhibition and become a bridge molecule connecting hormone metabolism and inflammation microenvironment regulation. This article aims to systematically review the chemical properties, plant sources, pharmacological activities, molecular mechanisms of action, medicinal properties, and clinical application prospects of 7-hydroxyflavanone, in order to provide comprehensive academic references for the in-depth development and transformation research of this natural product.

Chemical structure and physicochemical properties

7-Hydroxyflavanone, chemical name 2,3-dihydro-7-hydroxy-2-phenyl-4H-1-benzopyran-4-one, molecular formula C15H12O3, molecular weight 240.2580. Its core structure is the flavanone skeleton, which is the basic parent nucleus of dihydroflavones. Its characteristic is the chiral carbon atom at C-2 position (usually in racemic form), and the C ring (pyran ring) is partially saturated. Compared with flavonoids, the C2-C3 single bond of flavanones makes their conformation more flexible, but the non planarity of the C-ring also affects their binding mode with certain targets. The specificity of 7-hydroxyflavanone lies in the presence of a free phenolic hydroxyl group at the C-7 position of its A ring, which is a key pharmacophore for its antioxidant activity and participation in hydrogen bonding interactions.

From the analysis of physical and chemical properties, the calculated lipid water partition coefficient (LogP) of this compound is 2.8113, indicating that it has moderate lipophilicity, which is beneficial for transmembrane transport and bioavailability. The topologically polar surface area (TPSA) is 46.53 Å ², which is relatively small and further supports its good membrane permeability. The predicted value of its water solubility is 0.1078 mg/mL, which belongs to the category of slightly soluble to poorly soluble. This suggests that solubilization strategies may need to be considered in formulation development. It is worth noting that based on its physicochemical parameters, 7-hydroxyflavanone has a high blood-brain barrier permeability, which provides the possibility for its potential applications in the central nervous system, such as neuroinflammation regulation. In addition, preliminary pharmacological risk assessment showed that it has no inhibitory activity on hERG potassium channels (hERG inhibition: no), and the Ames test predicted a negative result (Ames test: 0.0), indicating that its cardiac toxicity risk and genetic toxicity risk are low, and it has a preliminary safety basis for further development.

Plant sources and extraction methods

7-Hydroxyflavones are widely present in various plants, especially in Fabaceae, Asteraceae, and Rutaceae, where they are abundant. Common plant sources include the skin and flowers of plants in the Glycyrrhiza and Citrus genera, as well as certain medicinal plants such as Psoralea corylifolia. In these plants, 7-hydroxyflavanones often coexist with other flavonoids and flavanone compounds, and are an important component of their secondary metabolites, which may participate in plant defense responses and signal regulation.

The extraction and separation method follows the conventional process of natural product chemistry. Firstly, organic solvents such as methanol, ethanol, acetone, or their aqueous solutions are used to extract or reflux the dried and crushed plant materials to obtain crude extracts rich in flavonoids. Subsequently, liquid-liquid extraction (commonly using ethyl acetate or n-butanol extraction) was used to preliminarily enrich the concentrated equipolar flavanone components. Further purification relies on various chromatographic techniques. Silica gel column chromatography is a commonly used separation method, which uses eluents of different polarities (such as petroleum ether ethyl acetate gradient system) for separation. High performance liquid chromatography (HPLC), especially preparative HPLC, has become a key technology for obtaining high-purity 7-hydroxyflavanones due to its high resolution. C18 reverse phase chromatography columns are often used, with methanol water or acetonitrile water (pH adjusted with a small amount of formic acid or acetic acid) as the mobile phase for elution. Structural identification involves the comprehensive use of ultraviolet spectroscopy (UV, characteristic absorption of flavanones), mass spectrometry (MS, providing molecular weight and fragment information), and nuclear magnetic resonance spectroscopy (NMR, especially 1H NMR and 13C NMR) to determine its planar and stereo structures. In recent years, green extraction techniques such as supercritical fluid extraction and microwave-assisted extraction have also been explored to improve extraction efficiency and selectivity.

Pharmacological activity research

7-Hydroxyflavones exhibit diverse pharmacological activities, and their research has expanded from initial aromatase inhibition to multiple disease fields.

1. Anti estrogen and anticancer activity As an effective inhibitor of aromatase, 7-hydroxyflavanone can directly reduce the biosynthesis of estrogen, thereby inhibiting the proliferation of estrogen dependent tumor cells. Studies have shown that it can inhibit the growth of breast cancer cells (such as MCF-7), and can induce cell cycle arrest and apoptosis. Its anti-cancer effect is not limited to hormone dependent tumors, but may also exert broad-spectrum anti-tumor effects through other pathways such as inducing oxidative stress and inhibiting metastasis related proteins.

2. antioxidant activity The phenolic hydroxyl group at position 7 of the A ring is a potent hydrogen donor that can scavenge free radicals (such as DPPH free radicals, ABTS free radical cations) and inhibit lipid peroxidation. This antioxidant capacity not only helps protect normal cells from oxidative damage, but may also indirectly affect their biological behavior by regulating the redox state within tumor or inflammatory cells.

3. anti-inflammatory activity This is an increasingly important aspect of pharmacological research on 7-hydroxyflavone ketone. In various in vitro inflammatory models (such as macrophages stimulated by lipopolysaccharide LPS) and in vivo models (such as carrageenan induced paw swelling in rats and acetic acid-induced increased peritoneal capillary permeability in mice), 7-hydroxyflavanone has shown significant anti-inflammatory effects. It can effectively inhibit the excessive production and release of inflammatory mediators, reduce tissue edema and inflammatory cell infiltration.

4. Other potential activities Based on its structural similarity, 7-hydroxyflavanone may also have antibacterial, antiviral, neuroprotective and other activities, but more experimental data is needed to support these aspects.

Mechanism of action and molecular targets

The multiple pharmacological activities of 7-hydroxyflavanone stem from its regulation of multiple key molecular targets and signaling pathways, and its mechanism of action is complex and synergistic.

1. Core target: Aromatase (CYP19)7-Hydroxyflavanone binds to the active site of aromatase through competitive or non competitive means, interfering with its binding to substrates such as androstenedione or testosterone, thereby directly inhibiting estrogen synthesis, which is the cornerstone of its anti estrogenic effect.

2. The core network of anti-inflammatory effects Its anti-inflammatory mechanism involves the regulation of multiple key inflammatory targets, forming a multi-target inhibition network

   • Inhibition of nuclear factor kappa B (NF - κ B) signaling pathway NF - κ B is the core transcription factor of inflammatory response. 7-Hydroxyflavanone can inhibit the degradation of I κ B α and nuclear translocation of NF - κ B p65 subunit, thereby blocking its transcriptional activity. This leads to a decrease in the expression of a series of pro-inflammatory cytokine genes downstream.
   • Regulating pro-inflammatory cytokines Through pathways such as NF - κ B, 7-hydroxyflavanone can significantly inhibit the production of key pro-inflammatory cytokines such as tumor necrosis factor - α (TNF - α) and interleukin-6 (IL-6).
   • Inhibition of inflammatory mediator synthase Research has shown that it can downregulate the expression of inducible nitric oxide synthase (NOS2) and cyclooxygenase-2 (PTGS2/COX-2), reduce the excessive production of inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2).
   • Affects STAT3 signal STAT3 is an important pathway connecting inflammation and tumors. 7-Hydroxyflavanone can inhibit the phosphorylation activation of STAT3 and block the expression of downstream pro survival and pro-inflammatory genes.
   • Regulating inflammasomes and pain perception Has the potential to inhibit the activation of CASP1 (cysteine protease-1), thereby affecting the maturation of cytokines such as IL-1 β. In addition, its potential regulatory effects on pain and inflammation related ion channels such as TRPV1 (transient receptor potential vanillic acid subtype 1) and TRPA1 (transient receptor potential anchor protein subtype 1) may be related to its ability to alleviate inflammatory pain.

3. Antioxidant and Cellular Protection Mechanisms In addition to directly scavenging free radicals, 7-hydroxyflavanone can also upregulate the expression of endogenous antioxidant systems in cells, such as HO-1 and NQO1 enzymes downstream of the Nrf2/ARE pathway, enhancing the cell's antioxidant defense ability.

These mechanisms do not exist in isolation. For example, its antioxidant effect can alleviate the activation of the NF - κ B pathway by oxidative stress; The microenvironment created by anti-inflammatory effects may indirectly affect the survival and hormone sensitivity of tumor cells. This multi-target characteristic gives 7-hydroxyflavanone a unique advantage in intervening in complex diseases such as chronic inflammation related cancers.

Evaluation of drug properties and pharmacokinetics

Although 7-hydroxyflavanone has shown good biological activity in vitro, its pharmacological properties still require systematic evaluation.

1. Absorption, distribution, metabolism, excretion (ADME)：

   • absorb Moderate LogP values and smaller TPSA indicate that it may have better intestinal absorption after oral administration. But its low water solubility may become a key factor limiting its dissolution and absorption rate.
   • distribution The predicted high blood-brain barrier permeability means that it can be distributed to the central nervous system, which is advantageous for the development of drugs for neuroinflammatory related diseases. The degree of binding between it and plasma proteins still needs to be experimentally clarified.
   • Metabolism As a flavanone compound, it is likely to undergo extensive metabolic transformations in the body. The main metabolic pathways may include: ① glucuronidation and sulfation of phenolic hydroxyl groups; ② Oxidation and ring opening of C ring; ③ Heterocyclic cleavage under the action of gut microbiota. These metabolites may affect their activity, duration, and toxicity. 7-Hydroxyflavanone itself, as a CYP19 inhibitor, may also affect the metabolism of other drugs that rely on this enzyme.
   • excretion Metabolites are mainly excreted through urine and bile.

2. Challenges and optimization strategies for drug development：

   • Poor water solubility This is the primary challenge. Pharmaceutical methods can be used to improve its solubility and bioavailability, such as making nanocrystals, solid dispersions, cyclodextrin inclusion complexes, or liposomes.
   • Fast metabolism Possible first pass effects and rapid binding metabolism may lead to insufficient exposure and short half-life in the body. The strategy includes structural modification (such as preparing prodrugs, protective derivatization of phenolic hydroxyl groups to improve metabolic stability) or co administration with metabolic enzyme inhibitors.
   • Targeted To enhance therapeutic efficacy and reduce systemic side effects, targeted delivery systems can be developed, such as using ligand modified nanoparticles to target tumor tissue or inflammatory sites.
   • safety Although there is no preliminary prediction of hERG inhibition and genotoxicity, it still needs to be validated through comprehensive preclinical toxicology studies (acute toxicity, chronic toxicity, reproductive toxicity, etc.).

At present, there is still a lack of publicly available data on the pharmacokinetics of the 7-hydroxyflavanone system, which is a key information gap that must be filled before it can be applied clinically.

Clinical application prospects and prospects

The multi-target pharmacological properties of 7-hydroxyflavanone provide broad prospects for its application in multiple disease fields, but also face many challenges.

1. Potential application directions：

   • Adjuvant therapy for hormone dependent tumors As a natural source aromatase inhibitor, it can be used in combination with existing drugs such as trastuzumab, or used to develop alternative/complementary therapies with fewer side effects, especially for patients who are intolerant to synthetic drugs.
   • Chronic inflammatory diseases The multi-target anti-inflammatory mechanism may provide new treatment options for diseases such as rheumatoid arthritis, inflammatory bowel disease, and asthma. Its analgesic potential (via TRPV1/TRPA1) is also worth exploring in chronic pain management.
   • Cancer chemoprevention Combined with its antioxidant, anti-inflammatory, and mild anti estrogenic effects, it may be used for cancer prevention in high-risk populations.
   • Neurodegenerative diseases Due to its antioxidant and anti-inflammatory properties, as well as its potential to penetrate the blood-brain barrier, it has research value in the intervention of neuroinflammatory diseases such as Alzheimer's disease and Parkinson's disease.

2. challenges faced：

   • Effectiveness issue Compared to the potent aromatase inhibitors used clinically (IC50 in the nM range), its IC50 of 65 μ M appears weaker and requires structural optimization to improve potency.
   • The complexity brought by multi-target targeting Multi targeting is both an advantage and a challenge, and it is necessary to clarify the balance between the main therapeutic effects and potential off target side effects within its therapeutic window.
   • Lack of complete preclinical and clinical data From in vitro activity to becoming a drug, it requires complex ADME, PK/PD, toxicology, and clinical trial validation, and is currently in the early stages of research.

3. Future research directions：

   • Research on Structure Modification and Structure Activity Relationship (SAR)Systematically modify the structure of 7-hydroxyflavanone (such as hydroxyl position and number, C-ring saturation, introduction of specific functional groups), aiming to enhance its activity against aromatase or specific inflammatory targets, and improve its pharmacokinetic properties.
   • Deep analysis of the mechanism of action Using chemical biology methods such as probe molecules and proteomics to discover new direct targets and draw more accurate action network maps.
   • Delivery system development Actively developing new nano drug delivery systems to address their solubility, stability, and targeting issues.
   • Collaborative effect research Exploring its combined application with existing chemotherapy drugs, targeted drugs, or immunomodulators may result in synergistic effects and reduced drug resistance.

Conclusion

7-Hydroxyflavones, as a naturally occurring flavonoid compound, have gradually demonstrated rich pharmacological activities including anti-tumor, antioxidant, and especially multi-target anti-inflammatory effects, starting from their clear aromatase inhibitory activity. It forms a synergistic network at the molecular level by regulating multiple key inflammation related targets such as NF - κ B, STAT3, PTGS2, NOS2, etc., which makes it unique in intervening in estrogen related diseases and chronic inflammatory diseases. Although there are still shortcomings in terms of efficacy, pharmacokinetics, and systematic research data, it is expected to overcome these limitations through the cross fusion of modern medicinal chemistry, pharmacy, and pharmacology methods for structural optimization, dosage form improvement, and mechanism deepening. In the future, with the continuous deepening of basic research and the promotion of translational medicine, 7-hydroxyflavanone and its derivatives are expected to develop from potential lead compounds into new drug candidates for tumor adjuvant therapy, chronic inflammation management, and other fields, providing a beneficial example for the modern development of natural products.