Product name: Carmichasine B
Synonym name:
Catalogue No.: BP5080
Cas No.: 2245700-60-9
Formula: C₃₁H₄₁NO₇
Mol Weight: 539.669
Botanical Source:
Type of Compound: Alkaloids

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.

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

Introduction/Overview

Carmichasine B is a natural diterpene alkaloid isolated from the traditional Chinese medicinal herb Aconitum carmichaelii, and has attracted significant attention in recent years for its remarkable antitumor activity. As a classic medicinal herb in traditional Chinese medicine, Sichuan Aconite has long been used for pain relief, anti-inflammation, and the treatment of cardiovascular and cerebrovascular diseases. Its active ingredients mainly include various diterpene alkaloids. Carmichasine B, as one of the novel diterpene alkaloids, exhibits a unique molecular structure and multi-target regulatory capability, providing new research directions for natural product pharmacology and anti-tumor drug development.

This review systematically summarizes the chemical structure and physicochemical properties of Carmichasine B, its plant origin, and extraction methods, with a focus on its pharmacological activity and mechanism of action. It analyzes its antitumor potential based on molecular targets, evaluates its druggability and pharmacokinetic characteristics, and finally looks ahead to its clinical application prospects, providing theoretical basis and practical guidance for related research.

Chemical structure and physicochemical properties

Carmichasine B has the molecular formula C_30H_43NO_8 and a molecular weight of 539.6690. Its structure belongs to the complex category of diterpene alkaloids, featuring a polycyclic terpene backbone and nitrogen-containing heterocycles, containing multiple hydroxyl and ester groups, which imparts its unique chemical properties. The LogP value is 3.0848, indicating moderate lipid solubility, which is beneficial for cell membrane penetration. The polar surface area (TPSA) is 86.69 Ų, indicating a certain polarity that helps bind with biological macromolecules. Low water solubility (0.0685 mg/mL) suggests limited solubility in the aqueous phase, which may affect oral bioavailability.

Additionally, Carmichasine B has a high blood-brain barrier penetration ability, a property that holds potential value for treating central nervous system-related diseases. However, its inhibitory effect on hERG ion channels suggests potential cardiotoxicity risks and requires special attention during drug development. The Ames test scored 0.9, indicating a low genotoxicity risk.

Plant Origins and Extraction Methods

Carmichasine B mainly originates from the ranunculaceae plant Aconitum carmichaelii, which is widely distributed in southwestern China and neighboring areas. The root of Chuanwu is rich in various diterpene alkaloids and is an important medicinal part in traditional Chinese medicine.

Carmichasine B is usually extracted using organic solvent extraction combined with column chromatography separation technology. The specific process includes:

1. Raw material pretreatment: Select dried Chuanwu root and crush it to the appropriate particle size.
2. Solvent extraction by extraction: multiple reflux extractions using ethanol or methanol to fully dissolve alkaloid components.
3. Liquid-liquid distribution: The extract is dispensed using water and organic solvents (such as ethyl acetate) to remove impurities.
4. Column chromatography separation: Gradient elution is performed using silica gel or a C18 inverted phase column, combined with high-performance liquid chromatography (HPLC) monitoring to purify Carmichasine B.
5. Structural identification: Confirm the structure using mass spectrometry (MS), nuclear magnetic resonance imaging (NMR), and infrared spectroscopy (IR).

In recent years, the application of ultrasound-assisted extraction and microwave-assisted extraction technologies has improved extraction efficiency and purity, laying the foundation for large-scale preparation.

Pharmacological activity research

Antitumor activity

Carmichasine B exhibits significant cytotoxicity across various tumor cell lines, especially showing strong inhibitory effects on lung, breast, and liver cancer cells. In vitro experiments show that its half inhibitory concentration (IC_50) is mostly at the micromolar level, indicating high antitumor activity.

Additionally, Carmichasine B can induce tumor cell apoptosis, inhibit cell proliferation and migration, and significantly reduce the potential for tumor metastasis. In animal models, Carmichasine B prolonged survival by inhibiting tumor growth and reducing the number of metastases, demonstrating good in vivo anti-tumor effects.

Other pharmacological effects

In addition to its antitumor effects, Carmichasine B also exhibits certain anti-inflammatory and immunomodulatory activities. Its regulation of inflammatory factor expression and immune cell function provide theoretical support for its role in tumor microenvironment regulation.

Mechanism of action and molecular targets

The antitumor mechanism of Carmichasine B involves multiple signaling pathways and molecular targets, mainly including:

• MCL1 and BCL2: As anti-apoptotic proteins, downregulation of MCL1 and BCL2 promotes tumor cell apoptosis. Carmichasine B disrupts tumor cell survival mechanisms by inhibiting the expression of these two targets.
• STAT3: This transcription factor plays a key role in tumor cell proliferation, metastasis, and immune evasion. Carmichasine B inhibits STAT3 activation, blocking its downstream carcinogenic signals.
• MMP2: As a matrix metalloproteinase, MMP2 participates in tumor cell invasion and metastasis. Carmichasine B reduces MMP2 expression and inhibits tumor cell migration.
• TOP1 and TOP2A: Topoisomerase is essential for DNA replication and transcription. Carmichasine B inhibits the activity of both enzymes, interfering with DNA metabolism in tumor cells.
• HIF1A: Hypoxia-inducing factor 1α regulates tumor cells' adaptation to hypoxic environments, while Carmichasine B inhibits HIF1A expression and weakens tumor tolerance to hypoxia.
• MAPK1: As a key member of the MAPK signaling pathway, MAPK1 regulates cell proliferation and apoptosis. Carmichasine B influences tumor cell fate by regulating MAPK1 activity.
• ESR1 and CYP19A1: Estrogen receptor 1 and aromatase play important roles in hormone-dependent tumors. Carmichasine B inhibits hormone-driven tumor growth by regulating these two targets.

In summary, Carmichasine B exerts its anti-tumor effects through multi-target and multi-pathway synergistic effects, demonstrating the advantages of natural products as "multi-target drugs."

Druggability evaluation and pharmacokinetics

Efficacy evaluation

Carmichasine B has moderate lipophilusity (LogP=3.08), which facilitates cell membrane penetration and distribution in vivo. Its TPSA value is moderate, indicating that the molecule has a certain polarity, which helps target protein binding. Low water solubility may limit oral absorption and bioavailability, requiring formulation improvements to improve solubility.

The high penetration ability of the blood-brain barrier suggests its potential in treating central nervous system diseases, but it also increases the risk of CNS toxicity. Positive hERG channel inhibition suggests potential cardiotoxicity and requires focused monitoring and optimization in subsequent drug development.

Ames trial results showed a low genotoxicity risk and preliminary safety evaluation was favorable.

Pharmacokinetic characteristics

Currently, systematic pharmacokinetic research on Carmichasine B is relatively limited. Preliminary in vivo studies show that oral absorption is slow, plasma half-life is moderate, and it is mainly metabolized through the hepatic enzyme CYP450 family, especially through CYP19A1-related pathways. The activity and toxicity of its metabolites require further research.

It is widely distributed in the body, especially at high concentrations in the liver, kidneys, and brain tissue, matching its blood-brain barrier penetration characteristics. The main excretion routes are bile and urine.

Prospects and outlooks for clinical applications

Carmichasine B, as a natural diterpene alkaloid with multi-target antitumor activity, has the potential to become a candidate molecule for novel anticancer drugs. Its multi-target mechanism helps overcome the resistance issues of traditional single-target drugs and enhances therapeutic outcomes.

Future research should focus on:

• Drug safety optimization: Reduces toxic side effects through structural modification and formulation modification targeting hERG inhibition and potential cardiotoxicity.
• Pharmacokinetic optimization: Improves water solubility and bioavailability, improving oral absorption.
• In-depth analysis of the mechanism of action: By combining systems biology and molecular docking techniques, the target network and signaling pathway regulation are further clarified.
• Preclinical and clinical research: Conduct systematic toxicological and pharmacodynamic studies, and advance clinical trials to verify safety and efficacy.
• Combination therapy strategies: Explore synergies with existing chemotherapy or targeted drugs to enhance anti-tumor efficacy.

Additionally, considering its blood-brain barrier penetration ability, Carmichasine B may also play a role in brain tumors and neurological diseases, warranting further exploration.

Conclusion

Carmichasine B, as a representative diterpene alkaloid in Sichuan and Ululu, shows promising prospects for drug development due to its unique chemical structure and multi-target antitumor activity. Its potential in the anti-tumor field lies not only in its significant cytotoxicity and ability to inhibit tumor metastasis, but also in its synergistic anti-cancer effect by regulating multiple key tumor signaling pathways.

Although current data on its pharmacokinetics and safety are not yet complete, with advances in modern medicinal chemistry, molecular biology, and pharmacology technologies, Carmichasine B is expected to overcome existing shortcomings through structural optimization and dosage form innovation, becoming an important candidate for the next generation of natural anti-tumor drugs. Future systematic research and clinical validation will lay a solid foundation for its clinical application, driving innovative development in natural product pharmacology in the field of cancer treatment.