Synonym name: dimethylacrylalkannin; β,β′－dimethylacrylalkannin
Catalogue No.: BP0260
Cas No.: 24502-79-2
Formula: C₂₁H₂₂O₆
Mol Weight: 370.401
Botanical Source: Lithospermum erythrospermum, Lithospermum euchromum, Alkanna tinctoria, Alkanna hirsutissima and Jatropha glandulifera

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

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

HPLC of Beta,beta-Dimethylacrylshikonin

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

Introduction/Overview

Beta,beta-dimethylacrylshikonin (hereinafter referred to as "dimethylacryl shikonin") is a natural product with significant biological activity, belonging to the hydroxy-1,4-naphthoquinone class compound. Due to their unique structure and diverse pharmacological activities, these compounds have attracted widespread attention in the field of natural product pharmacology in recent years. Dimethylacryliconin is mainly extracted from plants of the Lithospermum genus. Due to its potential in antitumor, anti-inflammatory, and antibacterial properties, it has become a hot topic in tumor treatment, especially in melanoma research. Melanoma, as a highly malignant skin tumor with a poor prognosis, is difficult to treat and urgently needs to develop new effective drugs. Dimethylacrylic shikonin demonstrates the ability to inhibit melanoma cell proliferation and induce apoptosis by regulating multiple key molecular targets, showing promising prospects for drug development.

This paper will systematically review the chemical structure and physicochemical properties of dimethylacrylic shikonin, plant origin and extraction process, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, and, combined with its potential applications in melanoma treatment, explore its future clinical development directions.

Chemical structure and physicochemical properties

The chemical structure of dimethylacryl shikonin belongs to the hydroxy-1,4-naphthoquinone class, with a molecular formula C22H26O5 and a molecular weight of 370.39. Its structural features include a 1,4-naphthoquinone core with hydroxyl and β,β-dimethylacryl side chains. The presence of this side chain gives the molecule strong hydrophobicity and a certain steric hindrance effect, which may affect its binding affinity with biological targets.

In terms of physicochemical properties, the LogP value of dimethylacrylicylshikonin is about 3.8, indicating good lipid solubility that facilitates cell membrane penetration, but may also affect its water solubility and bioavailability. The molecular polar surface area (TPSA) is 103.7 Ų, indicating moderate polarity and the ability to form hydrogen bonds with biological macromolecules. The molecule contains six hydrogen bond receptors, suggesting that it may form multi-point interactions when binding to protein targets. Low blood-brain barrier permeability suggests a lower risk of central nervous system side effects.

Currently, there are no clear reports on safety indicators such as hepatotoxicity, cardiotoxicity (including hERG channel inhibition), and genotoxicity (Ames test), and further systematic evaluation is needed.

Plant Origins and Extraction Methods

Dimethylacrylic shikonin is mainly found in the roots of Lithospermum species (such as Lithospermum erythrorhizon). Lithospermum plants are widely used in traditional Chinese medicine to treat inflammation, burns, and tumors. Their roots are rich in various natural naphthoquinone products, among which dimethylacrylicoylshikonin is one of the main active ingredients.

The extraction method typically uses organic solvent extraction combined with chromatography separation technology. Common extraction solvents include ethanol, methanol, and ethyl acetate. The extraction process requires controlling temperature and time to prevent degradation of active ingredients. After concentration, the extract was purified using silica gel column chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC), ultimately obtaining high-purity dimethacrylicylshikonin.

In recent years, green and efficient technologies such as supercritical CO2 extraction and microwave-assisted extraction have also been applied to the extraction of this compound, significantly improving extraction efficiency and purity, reducing the use of organic solvents, and meeting the environmental requirements of modern drug development.

Pharmacological activity research

Pharmacological studies on dimethylacrylic shikonin mainly focus on its antitumor effects, especially its role in melanoma cell lines. In vitro experiments have shown that this compound can significantly inhibit the proliferation of melanoma cells, induce cell cycle arrest, and apoptosis. Its antitumor activity is closely related to the regulation of apoptosis-related protein expression.

Additionally, dimethylacrylic shikonin has anti-inflammatory and antioxidant activities, reducing the activity of inflammatory factors such as NF-κB, alleviating inflammatory responses in the tumor microenvironment, and indirectly inhibiting tumor progression. Some studies have also indicated that it inhibits tumor cell migration and invasion, suggesting it may block the metastatic process of tumors.

Animal models are scarce, but preliminary data support its in vivo inhibition of melanoma growth, with low toxicity, demonstrating a good balance of safety and efficacy.

Mechanism of action and molecular targets

Dimethylacrylic shikonin exerts its anti-melanoma effect through multiple targets and multiple pathways. Its main targets include:

• BCL2: This protein is a member of the anti-apoptotic family, and dimethylacrylicylshikonin can downregulate BCL2 expression and promote apoptosis.
• TYR (tyrosinase): As a key enzyme in melanin synthesis, its activity regulates the biological behavior of melanoma cells.
• MAPK1 (ERK2), MAP2K1 (MEK1), BRAF: These are key members of the MAPK signaling pathway, involved in cell proliferation and survival regulation. Dimethylacrylicoylshikonin blocks tumor cell proliferation signals by inhibiting this pathway.
• TP53: As a tumor suppressor gene, activation of TP53 helps with cell cycle arrest and apoptosis. This compound may enhance apoptosis by activating the TP53 pathway.
• The NFKB1:NF-κB signaling pathway plays an important role in tumor inflammation and survival. Dimethylacrylic shikorin inhibits this pathway, weakening the anti-apoptotic capacity of tumor cells.
• NRAS, CDKN2A, MITF: These genes play key roles in the development of melanoma, regulating cell proliferation, differentiation, and apoptosis. Dimethylacrylic shikonin may regulate tumor cell fate by influencing these targets.

In summary, dimethylacrylic shikonin exerts its comprehensive anti-melanoma effect through synergistic regulation of multiple signaling pathways, demonstrating its potential as a multi-target antitumor drug.

Druggability evaluation and pharmacokinetics

From the perspective of druggability parameters, the molecular weight (370.39) and LogP (3.8) of dimethylacrylic shikonin met the basic drug affinity requirements in the Lipinski rule, suggesting good oral bioavailability potential. TPSA is 103.7 Ų, slightly above the ideal range (generally less than 90 Ų), which may affect cell membrane permeability but remains within acceptable limits.

Its number of hydrogen bond acceptors is 6, indicating moderate polarity, which facilitates stable binding to target proteins. The blood-brain barrier has low permeability, reducing the risk of toxic side effects in the central nervous system.

Currently, there is a lack of systematic research on pharmacokinetic parameters such as hepatic metabolic pathways, half-life, and plasma protein binding rate, and data on hepatotoxicity, cardiotoxicity, and genotoxicity remain unclear. Further improvement is needed through in vitro and vitro toxicology and pharmacokinetic studies.

Given its structural characteristics, dimethylacrylicylshikonin may be metabolized by the hepatic cytochrome P450 enzyme system, posing risks of metabolic activity or toxicity. Future research should focus on its metabolic stability and safety evaluation.

Prospects and outlooks for clinical applications

Dimethylacryl shikonin, as a natural naphthoquinone compound, demonstrates promising clinical development potential due to its multi-target anti-melanoma activity. Currently, melanoma treatment faces challenges such as targeted drug resistance and side effects from immunotherapy, and natural products provide new drug molecular sources and mechanisms of action.

In the future, dimethylacryl shikonin can be used as a monotherapy or in combination with existing targeted drugs (such as BRAF inhibitors) and immunotherapy as an adjunct to enhance efficacy and reduce the risk of resistance. Additionally, its anti-inflammatory and antioxidant effects help improve the tumor microenvironment and promote therapeutic outcomes.

During clinical translation, the following issues need to be addressed:

1. Safety Assessment: Systematic toxicological studies, especially tests for hepatorenal toxicity, cardiotoxicity, and genotoxicity.
2. Pharmacokinetic optimization: Enhancing bioavailability and in vivo stability through structural modification or drug carrier technologies.
3. Dosage Form Development: Developing dosage forms suitable for clinical applications, such as oral formulations, injections, or targeted delivery systems.
4. Clinical trial design: Conduct early-stage clinical trials to verify safety and preliminary efficacy.

Moreover, due to its multi-target properties, dimethylacryl shikonin may also expand into other therapeutic areas of malignancies and inflammation-related diseases, which is worth further exploration.

Conclusion

Beta, beta-dimethylacryl shikonin, as a hydroxy-1,4-naphthoquinone natural product derived from plants of the Lithospermum genus, has become an important subject of natural product pharmacological research due to its unique chemical structure and multi-target anti-melanoma activity. By regulating key molecules such as BCL2, MAPK pathways, TP53, and NF-κB, it exerts effects on inhibiting tumor cell proliferation and inducing apoptosis, demonstrating promising potential for drug development.

Although its safety and pharmacokinetic data are still incomplete, based on existing research, dimethylacrylic shikonin has the potential to become a novel anti-melanoma drug. In the future, it is necessary to integrate modern medicinal chemistry, pharmacokinetics, and clinical research to promote systematic development of this compound, providing new strategies and options for the treatment of melanoma and related diseases.