Product name: Isoeleutherin
Synonym name: (+)-allo-Eleutherin
Catalogue No.: BP4431
Cas No.: 1078723-14-4
Formula: C₁₆H₁₆O₄
Mol Weight: 272.3
Botanical Source:
Type of Compound:

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 Isoeleutherin

HNMR of Isoeleutherin

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

Introduction/Overview

Melanoma is an invasive malignant tumor originating from skin melanocytes. Its incidence rate continues to rise worldwide, and the prognosis of late patients is very poor. It is easy to develop resistance to traditional chemotherapy and radiotherapy. Therefore, the development of new, efficient, and low toxicity anti melanoma drugs is an important direction in current tumor pharmacology research. Natural products have always been an important source of innovative drug discovery due to their structural diversity and rich biological activity. Isoeleutherin (CAS number: 1078723-14-4), as a naphthopyranone compound isolated from traditional medicinal plants, has attracted much attention in recent years due to its significant anti proliferative and pro apoptotic activities in various tumor models, especially melanoma. Research has shown that isoquercetin can exert multi-target anti-tumor effects by intervening in multiple key signaling pathways and molecular targets, providing potential strategies for overcoming tumor heterogeneity and drug resistance. This article aims to systematically review the chemical properties, plant sources, pharmacological activities, mechanisms of action, medicinal properties, and application prospects of isoquercetin in the field of melanoma resistance, in order to provide comprehensive scientific references for the in-depth research and development of this compound.

Chemical structure and physicochemical properties

Isoquercetin is a natural product of naphthopyranone, with a molecular formula of C16H16O4 and a molecular weight of 272.3000. Its core structure is composed of a fused naphthalene ring and a pyranone ring, with specific substituents such as methoxy and methyl. This unique fused ring structure gives it a specific spatial conformation and electronic distribution, which is the structural basis for its interactions with various biomolecules such as enzymes and receptors.

From the analysis of physical and chemical properties, the lipid water partition coefficient (LogP) of isoquercetin is 2.5329, indicating that the compound has moderate lipophilicity, which is conducive to its penetration of the cell membrane and entry into the cell to exert its effects. Its topological polar surface area (TPSA) is 52.6000 Å ², which is relatively low, further indicating its good membrane permeability. However, its water solubility is poor, about 0.0610 mg/mL, which may pose challenges in formulation development and in vivo administration routes. It is worth noting that based on its physicochemical parameters prediction, isoquercetin has a high blood-brain barrier permeability, which provides unique advantages for its potential application in the treatment of melanoma that may undergo brain metastasis. In addition, preliminary pharmacological risk assessment showed negative hERG inhibition, indicating a low risk of inducing cardiac toxicity (such as long QT syndrome); However, the Ames test result is 1.5, indicating a possible slight risk of mutagenicity and requiring close attention and in-depth evaluation in subsequent development.

Plant sources and extraction methods

Isoquercetin is mainly derived from the Iridaceae family of the Allium genus（Eleutherine）Plants, especially American red onions（Eleutherine bulbosa (Mill.) Urb.， Also known as Eleutherine americana）The bulbs. This genus of plants has a long history of application in traditional medicine in Southeast Asia and South America, often used to treat inflammation, infections, cardiovascular diseases, and digestive system diseases.

The extraction and separation of isoquercetin from plant materials usually use organic solvent extraction combined with chromatographic separation technology. The common process is as follows: first, the dried plant bulbs are crushed, and polar organic solvents such as methanol, ethanol, or acetone are used for cold soaking or heating reflux extraction to obtain the crude extract. Subsequently, the crude extract was preliminarily segmented using liquid-liquid extraction methods (such as ethyl acetate, chloroform, etc.). The obtained fraction rich in naphthopyranone compounds is further separated and purified by column chromatography, using commonly used stationary phases such as silica gel and reverse phase silica gel (such as C18), and mobile phases of different proportions of petroleum ether ethyl acetate or methanol water systems. Monitor by thin layer chromatography (TLC) or high performance liquid chromatography (HPLC), and ultimately obtain high-purity isoquercetin monomer by preparative HPLC or recrystallization methods. In recent years, green extraction techniques such as supercritical fluid extraction have also been explored to improve extraction efficiency and selectivity.

Pharmacological activity research

A large number of in vitro and in vivo pharmacological studies have confirmed that isoquercetin has a wide range of biological activities, and its core research focus is on the field of anti-tumor, especially targeting melanoma.

1. Anti melanoma activity Multiple cell experiments have shown that isoquercetin exhibits significant concentration - and time-dependent growth inhibitory activity against various human melanoma cell lines (such as A375, SK-MEL-28, B16-F10, etc.), with IC50 values typically at the micromolar level. Its function is not limited to inhibiting cell proliferation, but can also effectively induce cell cycle arrest (often occurring in the G2/M or S phase) and cell apoptosis.
2. Inducing cell apoptosis Typical morphological changes of apoptosis, such as cell shrinkage, chromatin condensation, and formation of apoptotic bodies, can be observed in melanoma cells treated with eosin. Flow cytometry analysis showed a significant increase in the proportion of Annexin V positive cells, accompanied by activation of key apoptosis executing proteins such as Caspase-3, -8, and -9.
3. Inhibit cell migration and invasion Through scratch healing experiments and Transwell chamber experiments, it has been confirmed that isoquercetin can effectively inhibit the migration and invasion ability of melanoma cells, indicating its potential for anti-tumor metastasis.
4. Other activities In addition to its anti-tumor activity, research also suggests that isoquercetin may have antioxidant, anti-inflammatory, and antibacterial effects. These auxiliary activities may synergize with its core anti-tumor effects, such as enhancing therapeutic efficacy by regulating the tumor microenvironment.

Mechanism of action and molecular targets

The anti melanoma effect of isoquercetin is not achieved through a single pathway, but involves a complex multi-target regulatory network. Existing research has preliminarily revealed its interactions with multiple key targets involved in the development and progression of melanoma

1. Regulating the apoptotic pathway Isoquercetin can downregulate the expression of anti apoptotic protein BCL2 and may also affect the activity of TP53 (p53), thereby relieving the inhibition of mitochondrial apoptosis pathway, promoting cytochrome C release, and ultimately activating the Caspase cascade reaction, inducing cell apoptosis.
2. Intervention in MAPK/ERK signaling pathway This pathway is abnormally activated in melanoma, especially in types carrying BRAF or NRAS mutations. Research has shown that isoquercetin can inhibit the phosphorylation or activity of key kinases in this pathway, such as BRAF, MAP2K1 (MEK1), and MAPK1 (ERK2), thereby blocking downstream signaling pathways that promote cell proliferation and survival.
3. Inhibition of NF - κ B signaling pathway NFKB1 (NF - κ B) is an important inflammatory and survival transcription factor, and its sustained activation is closely related to tumor drug resistance and metastasis. Isoquercetin can inhibit the activity of I κ B kinase (IKK) or the degradation of I κ B α, prevent NF - κ B nuclear translocation, and reduce the expression of downstream pro survival and pro-inflammatory genes.
4. Affects cell cycle regulation The cell cycle arrest caused by isoquercetin is related to its regulation of the expression of cyclins, cyclin dependent kinases (CDKs), and CDK inhibitors (such as p16INK4a, encoded by the CDKN2A gene). Stagnation of cell cycle progression is achieved by upregulating CDKN2A or downregulating the activity of specific Cyclin CDK complexes.
5. Inhibition of enzymes related to melanin production Isoquercetin exhibits certain inhibitory activity against tyrosinase (TYR). Although this is mainly related to skin whitening, in melanoma, TYR acts as a differentiation marker and its activity is complexly regulated, which may indirectly affect the biological behavior of tumor cells.
6. Interaction with protein kinase C There are studies suggesting that isoquercetin may affect the activity of PRKCA (protein kinase C alpha), which plays multiple roles in cell proliferation, differentiation, and apoptosis signaling transduction. The specific mechanism of action of PKC needs further clarification.

In summary, isoquercetin exerts a synergistic anti-tumor effect by simultaneously acting on multiple targets such as BCL2, TP53, MAPK pathway, NF - κ B pathway, and cell cycle checkpoint, which may be its potential advantage in overcoming single target drug resistance.

Evaluation of drug properties and pharmacokinetics

Although isoquercetin has shown good pharmacological activity in vitro, its successful development as a drug highly depends on systematic pharmacological evaluation and pharmacokinetic studies. At present, the preclinical pharmacokinetic data of isoquercetin is not complete, but based on its physicochemical properties and preliminary research, the following analysis can be conducted:

1. Absorption and distribution Moderate LogP values and lower TPSA indicate that oral absorption may be better, but poor water solubility may limit its dissolution rate and degree in gastrointestinal fluids, thereby affecting bioavailability. The use of nanoformulations, solid dispersions, or cyclodextrin inclusion techniques for solubilization is a potential solution. Its high blood-brain barrier permeability prediction is a significant advantage in the treatment of melanoma brain metastases.
2. Metabolism and excretion As a naphthopyranone compound, isoquercetin is likely to undergo phase I (such as oxidation and reduction by cytochrome P450 enzymes) and phase II (such as glucuronidation and sulfation) metabolism in the liver. Identifying its main metabolic enzymes, metabolites, and activities is crucial for evaluating drug drug interactions and individual differences. Its excretion pathway may mainly be through bile and urine.
3. Preliminary Safety Assessment The negative inhibition of hERG is a positive signal, but the potential mutagenicity of Ames test (result 1.5) must be confirmed by a more comprehensive combination of genetic toxicity tests (such as micronucleus test, chromosome aberration test) to assess the risk. In addition, acute and long-term toxicity tests are required to evaluate its toxicity to major organs.
4. Formulation development challenges The core challenge lies in improving its water solubility and chemical stability. Exploring appropriate drug delivery systems (such as liposomes, polymer micelles, prodrug strategies) is crucial for improving their in vivo delivery efficiency and reducing toxic side effects.

Clinical application prospects and prospects

As a natural lead compound with multiple targets against melanoma, isohongcong B has broad clinical application prospects, but also faces many challenges.

Potential advantages and prospects：
1. Multi target mechanism of action Targeting the complex signaling network of melanoma, multi-target drugs may be more effective in inhibiting tumor growth and delaying the development of drug resistance. The characteristic of isoquercetin makes it a potential candidate for monotherapy or combination therapy.
2. Blood-brain barrier penetrability For common brain metastases in advanced melanoma, the efficacy of existing drugs is limited. The high BBB permeability potential of isoquercetin provides a unique opportunity for its treatment of brain metastases.
3. Combined application with traditional therapy or immunotherapy Exploring the synergistic effects of isoquercetin with dalafenib/trametinib (targeting BRAF/MEK), chemotherapy drugs (such as dacarbazine), or immune checkpoint inhibitors (such as PD-1 antibodies) may lead to better therapeutic efficacy and overcome drug resistance.
4. Structural optimization and derivative development Using it as the parent nucleus for structural modification aims to enhance activity, improve water solubility, and reduce potential toxicity, which is an important direction in pharmaceutical chemistry research.

Challenges faced and future research directions：
1. In depth study on the mechanism of action It is necessary to clarify more accurately the direct interaction mode (whether it is direct binding or indirect regulation) between it and various targets (such as PRKCA, NRAS, etc.), and use gene knockout/knockdown techniques to verify the necessity of key targets in mediating their effects.
2. Preclinical development of the system A comprehensive pharmacokinetic study (ADME), safety pharmacology, and toxicology evaluation must be completed to clarify its therapeutic window. Pharmaceutical research needs to address the issues of solubility and stability.
3. Pharmacodynamic validation in vivo It is necessary to validate the anti-tumor efficacy and metastasis inhibition ability of monotherapy and combination therapy in more and more clinically relevant melanoma animal models, such as patient derived tumor xenograft models.
4. Risk benefit assessment The potential genetic toxicity risk is a core safety issue that must be strictly monitored and evaluated in future development.

Conclusion

Isoquercetin is a natural compound of naphthopyranone with significant anti melanoma activity discovered from traditional medicinal plants. It exerts multiple pharmacological effects such as inducing apoptosis, inhibiting proliferation, blocking the cell cycle, and resisting migration and invasion by regulating multiple signaling pathways such as BCL2, TP53, MAPK, and NF - κ B, demonstrating the characteristics of multi-target anti-tumor drugs. Despite challenges such as poor water solubility and potential genetic toxicity in drug development, its unique structure, clear biological activity, and especially its potential blood-brain barrier penetration ability make it of significant exploration value in the field of anti melanoma drug research and development. Future research should focus on in-depth analysis of its molecular action network, systematic preclinical pharmacokinetics and safety evaluation, and actively carry out derivative design and optimization based on its structure. Through interdisciplinary collaboration, isoquercetin is expected to gradually develop from a promising natural lead compound into a novel therapeutic weapon against melanoma, a malignant disease.