Synonym name:
Catalogue No.: BP0341
Cas No.: 3895-92-9
Formula: C₂₁H₁₈ClNO₄
Mol Weight: 383.828
Botanical Source:

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 Chelerythrine chloride

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

Introduction/Overview

Chelerythrine chloride (CAS No.: 3895-92-9) is a compound derived from the natural plant genus Chelidonium, an alkaloid that has attracted much attention for its remarkable biological activity and unique molecular mechanism. As an effective inhibitor of protein kinase C (PKC), cecetylline chloride can penetrate cell membranes, regulate multiple signaling pathways, induce apoptosis and autophagy, and demonstrate broad pharmacological potential. In recent years, with the deepening development of tumor biology and molecular pharmacology, cestrine chloride has shown significant therapeutic value in the study of malignant tumors such as liver cancer, becoming a research hotspot in the field of natural product pharmacology.

This paper aims to systematically review the chemical structure and physicochemical properties, plant origin and extraction methods, pharmacological activity, and mechanism of action of Cestragalus chloride red alkaloid. Combined with its druggability evaluation and pharmacokinetic characteristics, it explores its potential clinical application prospects in diseases such as liver cancer, providing theoretical basis and research directions for subsequent drug development and clinical translation.

Chemical structure and physicochemical properties

Chloride white celandine red alkaloid is a benzoisoquinoline alkaloid with the molecular formula C21H18ClNO4 and a molecular weight of 387.83. Its structural features include a benzoisoquinoline framework with multiple methoxy substituents and a chloride ion coordination, which imparts good lipophilicity and membrane permeability. Its LogP value is 1.89, indicating moderate lipid solubility, which is beneficial for intracellular targeting.

The topological surface area (TPSA) of celandine chloride red alkaloid is 55.84 Ų, with 4 hydrogen bond acceptors, indicating certain polarity and hydrogen bonding ability in intermolecular interactions, which facilitates binding to protein targets. Its high blood-brain barrier permeability suggests that this compound also holds potential value in research on central nervous system diseases.

However, chloride cysthesine has certain hepatotoxicity and cardiotoxicity and inhibits hERG channels. A positive Ames test indicates a genotoxic risk, posing safety challenges for clinical application.

Plant Origins and Extraction Methods

Chloride white celandine red alkali mainly comes from the papavery genus Chelidonium majus L. and related plant species. As a traditional Chinese medicinal herb, Baiqucai is widely distributed in parts of Europe and Asia, with its rhizomes and above-ground parts rich in isoquinoline alkaloids.

Common methods for extracting chlorinated white celandine red alkali include:

1. Solvent extraction method: Using organic solvents such as methanol, ethanol, or ethyl acetate to extract dried plant materials, then enriching alkaloid components through liquid-liquid partitioning and acid-base adjustment.

2. Column chromatography separation: The crude extract is separated and purified using silica gel or a C18 reversed-phase column, and high-purity chloride celandine red alkaloid is obtained by gradient elution.

3. High-performance liquid chromatography (HPLC) detection: Used for qualitative and quantitative analysis of the content of chlorinated celandine red alkaloid in extracts, ensuring the stability and repeatability of the extraction process.

In recent years, the application of ultrasound-assisted extraction and microwave-assisted extraction technologies has improved extraction efficiency and purity, providing technical support for industrial production.

Pharmacological activity research

As a PKC inhibitor, white celandine chloride red alkaloid exhibits multiple pharmacological activities, mainly including anti-tumor, anti-inflammatory, antibacterial, and neuroprotective effects.

Antitumor activity

Chloride white crustine shows significant cytotoxicity in various tumor cell lines, especially in liver cancer cells, inducing apoptosis and autophagy by inhibiting PKC activity (IC50 about 660 nM) and regulating the function of Bcl-2 family proteins. Its IC50 inhibition of Bcl-XL-Bak BH3 peptide binding is 1.5 μM, which can replace Bax from Bcl-XL, disrupt the protective function of anti-apoptotic proteins, and promote programmed cancer cell death.

Additionally, chlorogene red alkaloid can regulate tumor-related signaling pathways such as STAT3, PI3K/AKT, NF-κB, inhibiting tumor cell proliferation, migration, and invasion, reducing MMP9 expression, and suppressing malignant progression in the tumor microenvironment.

Anti-inflammatory and immunomodulatory

By inhibiting the PKC and NF-κB signaling pathways, chlorocythine shows anti-inflammatory activity, reduces the secretion of inflammatory factors such as TNF-α and IL-6, alleviates inflammatory responses, and has potential therapeutic value for immune-related diseases.

Other activities

Some studies have shown that brocadine chloride has protective effects on nerve cells and may slow the progression of neurodegenerative diseases by regulating apoptosis and autophagy mechanisms. Moreover, its antibacterial activity also makes its application possible in infectious diseases.

Mechanism of action and molecular targets

The main mechanism of action of celandine chloride is concentrated on inhibition of the protein kinase C (PKC) family. As a key enzyme in cell signaling, PKC is involved in cell proliferation, differentiation, apoptosis, and metabolic regulation. Chloride white celandine red alkaloid competitively binds to the catalytic site of PKC, blocking its kinase activity and inhibiting downstream signal transduction.

In addition, chloride white cystrial red alkaloid is especially crucial for regulating Bcl-2 family proteins. It can inhibit the binding of Bcl-XL to Bak BH3 peptide, promote the release of Bax from Bcl-XL, and activate mitochondrial apoptosis. This mechanism is especially pronounced in liver cancer cells, promoting programmed death of cancer cells.

Molecular targets also include:

• STAT3: Chlorophylline inhibits STAT3 phosphorylation, blocks its transcriptional activity, and suppresses tumor cell growth and survival.
• PIK3CA/AKT1: Interferes with the PI3K/AKT signaling pathway, regulates cellular metabolism and apoptosis.
• MMP9: Downregulates stromal metalloproteinase 9, reducing tumor invasion and metastasis capacity.
• EGFR: Inhibits epidermal growth factor receptor signaling and blocks cell proliferation signals.
• TP53: promotes cell cycle arrest and apoptosis by regulating p53-related pathways.
• NFKB1: Inhibits NF-κB activity, reduces inflammation and tumor survival signaling.

In summary, cytrolin chloride red aline achieves its anti-tumor and cellular regulatory functions through multi-target and multi-pathway synergistic effects.

Druggability evaluation and pharmacokinetics

The molecular weight (387.83) and LogP (1.89) of chloride red alkaloid comply with the Lipinski rule, theoretically providing good oral bioavailability and cellular permeability. Its TPSA value is moderate, which is beneficial for target binding and in vivo distribution.

However, multiple safety risks have been exposed in druggability evaluations:

• Hepatotoxicity: Chlorophylline can trigger toxic reactions in liver cells, limiting its long-term or high-dose use.
• Cardiotoxicity: Its effects on cardiac electrophysiology, especially inhibition of hERG channels, increase the risk of arrhythmias.
• Genotoxicity: A positive Ames test suggests possible mutagenic risk and requires further safety assessment.

Pharmacokinetics, white celandine chloride has high blood-brain barrier permeability, suggesting potential application value in central nervous system diseases, but central toxicity is also warranted.

Currently, data on its metabolic pathways, half-life, and excretion modes in vivo are not yet complete. Systematic pharmacokinetic studies are needed in the future to support clinical dose design and safety evaluation.

Prospects and outlooks for clinical applications

With its significant PKC inhibitory activity and multi-target regulatory effects, white celandine chloride shows broad application prospects in the treatment of malignant tumors such as liver cancer. Its dual mechanisms of inducing apoptosis and autophagy offer new ideas for overcoming tumor drug resistance and improving treatment outcomes.

However, its potential hepatotoxicity, cardiotoxicity, and genotoxicity limit its direct clinical application. Future research should focus on:

1. Structural modification and derivative development: Chemical modification reduces toxicity, improving selectivity and safety.
2. Nanocarriers and targeted delivery: Utilizing nanotechnology to achieve targeted drug delivery and reduce systemic toxic side effects.
3. Combination therapy strategy: combine with other antitumor drugs to achieve synergistic effects and reduce single-agent dosage.
4. Preclinical safety evaluation: Systematic toxicological and pharmacokinetic studies are conducted to clarify safe dosage ranges.
5. Expansion of multiple disease indications: exploring its potential applications in neurodegenerative diseases and inflammatory diseases.

Overall, as a candidate molecule for natural product drug development, chloride white celandine red alkaloid has significant research and development value, but its clinical translation still faces multiple challenges.

Conclusion

As a naturally derived PKC inhibitor, Celandine chloride demonstrates significant pharmacological activity in anti-tumor treatment, especially liver cancer, due to its unique chemical structure and multi-target regulatory mechanism. Its ability to induce apoptosis and autophagy offers new strategies for tumor treatment. However, safety issues in druggability, especially hepatotoxicity and cardiotoxicity, have become the main bottlenecks in clinical application.

Future research should focus on structural optimization, targeted delivery, and combination therapy strategies, while strengthening pharmacokinetics and toxicology studies to promote the transition from laboratory research to clinical application. As an important representative in the field of natural product pharmacology, in-depth research on cesy chloride red alkaloid not only helps enrich the natural product drug library but also provides new ideas and possibilities for treating major diseases such as liver cancer.