Synonym name:
Catalogue No.: BP0333
Cas No.: 24316-19-6
Formula: C₁₈H₂₁NO₄
Mol Weight: 315.369
Botanical Source: Alkaloid from Cephalotaxus harringtonia var. harringtonia, Cephalotaxus harringtonia var. drupacea, Cephalotaxus fortunei, Cephalotaxus hainanensis, Cephalotaxus wilsoniana, Cephalotaxus sinensis and Cephalotaxus oliveri (Cephalotaxaceae)

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 Cephalotaxine

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

Introduction/Overview

Cephalotaxine is an important natural benzoazaza alkaloid, first isolated and identified from Eucalyptus species. As a class of natural products with unique structures and bioactivity, tritaxine and its derivatives have attracted widespread attention in the field of antitumor drug development. In recent years, with further research into its pharmacological activity and mechanism of action, tricaptaxine has shown potential application value in the treatment of various malignant tumors such as lung cancer. This paper aims to systematically review the chemical structure, plant origin, pharmacological activity, mechanism of action, and druggability evaluation of tricarcinine, explore its clinical application prospects, and provide a theoretical basis for subsequent research and drug development.

Chemical structure and physicochemical properties

Tricapsuline has the molecular formula C18H21NO4, molecular weight 315.36, and CAS number 24316-19-6. Its structure is the basic parent of benzoazepinate alkaloids, including benzoazezein heterocyclic rings, organic heteropentacyclic rings, secondary alcohols, enol ethers, tertiary amino groups, and cyclic acetals, among other functional groups. The LogP value of tricyclane is about 1.5, indicating moderate lipid solubility, which facilitates penetration of cell membranes. TPSA (Topological Polar Surface Area) is 61.76 Ų, indicating certain polarity that facilitates binding to biological targets. The molecule contains five hydrogen bond receptors, which may enhance its interaction with protein targets.

In terms of physical and chemical properties, tricanine is a white to pale yellow crystalline solid with good thermal and light stability. The polycyclic systems and heterocyclic features in its structure endow it with unique chemical reactivity and facilitate subsequent chemical modifications and derivative synthesis.

Plant Origins and Extraction Methods

Tricarpine is mainly found in plants of the genus Cephalotaxus, especially in the branches, leaves, and seeds of Cephalotaxus spp., where its content is relatively high. Species of the Tricarpus genus are widely distributed throughout East Asia and are an important source of traditional Chinese medicinal materials. Due to its relatively low content, optimizing extraction and purification processes is key to achieving industrialized production of tricapsis soda.

Traditional extraction methods mostly rely on organic solvent extraction combined with acid-base adjustment. The specific process includes: crushing the dried Tridentia plant material, reflux extraction with methanol or ethanol, extracting the extract by concentration and separating alkaloids by acid-base methods, followed by column chromatography (such as silica gel columns, C18 reversed phase columns) for purification. In recent years, the application of ultrasound-assisted extraction, microwave-assisted extraction, and high-performance liquid chromatography (HPLC) purification technologies has significantly improved extraction efficiency and purity.

Moreover, with the development of biosynthesis and semi-synthesis technologies, the synthesis of triscapaline and its derivatives through plant cell culture or microbial fermentation pathways has become a research hotspot, aiming to address the dual challenges of limited natural resources and environmental protection.

Pharmacological activity research

Research on the pharmacological activity of tritaxane mainly focuses on its anti-tumor effects, especially showing significant cytotoxicity and antiproliferative effects in the field of lung cancer. In vitro experiments show that tricyclaneine can inhibit the proliferation of various lung cancer cell lines, inducing cell cycle arrest and apoptosis. Additionally, tricycline has relatively low toxicity to normal cells and shows certain selectivity.

In animal models, tricyclanesine and its derivatives can significantly inhibit the growth of lung cancer tumors and extend survival in experimental animals. Its anti-tumor effects are not limited to lung cancer, but also involve various solid tumors such as breast cancer and stomach cancer, demonstrating broad anti-cancer potential.

In addition to its antitumor activity, tricescarcinine also exhibits certain anti-inflammatory, antioxidant, and immunomodulatory effects, which may provide synergistic effects for its comprehensive tumor treatment. Currently, toxicological research on it is insufficient, and safety indicators such as hepatotoxicity and cardiotoxicity still require further evaluation.

Mechanism of action and molecular targets

The antitumor mechanism of tricyclamine involves multiple signaling pathways and key molecular targets. Studies show that its main targets include BCL2, STAT3, ESR2, MAPT, PIK3CG, RELA, MAPK1, CASP9, MAPK8, and PPARG.

• BCL2: Triaceal anesine promotes tumor cell apoptosis by downregulating the expression of the anti-apoptotic protein BCL2, relieving survival pressure.
• STAT3: As an important regulatory factor for tumor cell proliferation and immune evasion, inhibition of STAT3 activity is one of the key mechanisms of tritaxane in anti-cancer activities.
• ESR2 (estrogen receptor β): Regulates tumor cell proliferation and differentiation; tricyclaneine may play a role by modulating ESR2-mediated signaling pathways.
• MAPT (microtubule-associated protein Tau): affects the stability of the cytoskeleton, and tricapsuline influences cell cycle and migration capacity by modulating MAPT.
• PIK3CG :P key member of the I3K signaling pathway, involved in cell survival and metabolic regulation. Tricycline inhibits its activity and blocks tumor cell proliferation signals.
• RELA (NF-κB p65 subunit): regulates inflammation and cell survival. Tricarcinine inhibits RELA activity, helping to suppress pro-cancer inflammatory responses in the tumor microenvironment.
• MAPK1 and MAPK8: Involved in cellular stress response and apoptosis signaling, tricyclaneline promotes tumor cell death by modulating the MAPK pathway.
• CASP9: A key endogenous apoptosis initiator enzyme, tricyclaneine activates CASP9 and induces programmed cell death.
• PPARG: A member of the nuclear receptor family, regulates lipid metabolism and cell differentiation. Tricargonine may regulate tumor metabolic status through PPARG.

Overall, tricyclanesine inhibits tumor cell proliferation, migration, and survival through multi-target and multi-pathway synergistic effects, promotes apoptosis, and demonstrates a complex and effective anti-cancer mechanism.

Druggability evaluation and pharmacokinetics

From the perspective of druggability parameters, tricapsuline has relatively ideal medicinal properties. Its molecular weight of 315.36 complies with the Lipinski rule, which is beneficial for oral absorption. A LogP value of 1.5 indicates moderate lipid solubility, ensuring membrane penetration without excessive hydrophobicity that reduces bioavailability. TPSA was 61.76 Ų, indicating good polarity when targeted binding within cells.

Tritaxane has high blood-brain barrier permeability, indicating its potential for treating central nervous system-related diseases, but this also suggests that its potential neurotoxicity risks warrant attention. Data on hepatotoxicity, cardiotoxicity, and Ames-related mutagenicity assays are still unclear, and further systematic safety evaluation is needed. Notably, trisalane does not inhibit hERG channels, suggesting a lower risk of cardiotoxicity.

Currently, there are few public reports on pharmacokinetics. Preliminary studies show that tricycline is well absorbed orally, has a moderate plasma half-life, and can maintain effective concentrations in the body. Its metabolic pathway may involve enzymatic reactions in the liver, and the metabolites and their toxicity still require further study. In the future, pharmacokinetic studies in vivo and in vitro are needed to clarify its absorption, distribution, metabolism, and excretion (ADME) characteristics, providing a basis for clinical formulation design and administration regimens.

Prospects and outlooks for clinical applications

As a naturally occurring antitumor active molecule, tricyclanesine and its derivatives show broad application prospects in lung cancer treatment. As one of the malignant tumors with the highest incidence and mortality rates worldwide, lung cancer urgently needs novel, efficient, and low-toxicity treatments. Tricyclanesine regulates the biological behavior of tumor cells through multiple targets, offering a new therapeutic strategy.

Currently, tricapaline derivatives based on trisaline esters, such as tricapsaline ester compounds, have entered clinical trial stages, demonstrating good anticancer activity and tolerability. Future research should focus on optimizing the structure of tricyclane, improving its bioavailability and targeting, and reducing potential toxic side effects. In addition, combining modern drug delivery systems (such as nanocarriers and targeted drug delivery technologies) can further enhance clinical efficacy.

At the same time, the potential of tricyclaneine in combination therapy is also worth noting. By combining them with chemotherapy drugs, immunomodulators, or targeted drugs, synergistic anti-cancer effects can be achieved, overcoming the problem of single-drug resistance.

Future research should also strengthen systematic evaluation of the safety and pharmacokinetics of tritaxane, promote its transition from laboratory research to clinical application, and ultimately realize its clinical value in the treatment of lung cancer and other malignant tumors.

Conclusion

Tricyclane, as a naturally occurring benzoazine alkaloid with a unique structure and significant bioactivity, has become an important research subject in the treatment of lung cancer and other malignancies, thanks to its multi-target anti-tumor mechanism and excellent druggability. Although research on its clinical application is still in its early stages, its potential drug development value cannot be ignored. In the future, through chemical modification, optimized drug delivery, and systematic pharmacological and toxicological research, tricarceline is expected to become an important component of the new generation of anticancer drugs. Ongoing and in-depth basic and translational research will pave the way for clinical application, driving the development and innovation of natural product pharmacology.