Synonym name: Lycoricidinol
Catalogue No.: BP0978
Cas No.: 29477-83-6
Formula: C₁₄H₁₃NO₇
Mol Weight: 307.258
Botanical Source: Alkaloid from Narcissus incomparabilis, all Narcissus spp. examined, and present in many other Amaryllidaceae spp. Also found in the Texas grasshopper Brachystola magna

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.

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

Introduction/Overview

Narciclasine (CAS No.: 29477-83-6) is a natural product derived from plants of the genus Narciclasine, belonging to the isoquinoline alkaloids. Since its first isolation from Narcissus spp. in the mid-20th century, Narcissus cycline has attracted widespread attention due to its unique biological activity, especially its potential in antitumor treatment. As a plant growth regulator, Narcissandin's ability to regulate the Rho/Rho kinase/LIM kinase/cofilin signaling pathways not only plays an important role in plant physiology, but also provides a molecular basis for its function in cytoskeletal remodeling and cell motility. In recent years, with advances in molecular pharmacology and medicinal chemistry, the antitumor mechanisms of Narcissian Cycline have gradually been revealed. Its targets cover multiple key signaling molecules and transcription factors such as MCL1, BCL2, and STAT3, showing promising prospects for drug development.

This paper will systematically review the chemical structure and physicochemical properties of Narcissusin, plant origin and extraction methods, pharmacological activity and mechanism, druggability evaluation, and pharmacokinetic characteristics, and finally discuss its clinical application potential, aiming to provide comprehensive reference materials for researchers and drug developers in the field of natural product pharmacology.

Chemical structure and physicochemical properties

The molecular formula of Narcissus cycline is C16H15NO5, with a molecular weight of 307.2580. Its structure belongs to the isoquinoline alkaloids, featuring polyhydroxyl-substituted benzene rings and nitrogen-containing heterocycles, with multiple hydroxyl and ketone groups within the molecule, giving it high polarity. The unique chemical structure determines its biological activity and ability to bind to targets.

In terms of physicochemical properties, the LogP value of Narcissus Cycline is about -0.4825, indicating strong hydrophilicity, with a water solubility of 10.2780, indicating good water solubility. Its topological pole surface area (TPSA) is 128.48 Ų, and a higher TPSA value is usually associated with poor cell membrane permeability, which may affect its oral bioavailability. The low permeability of the blood-brain barrier suggests its limited distribution in the central nervous system, which helps reduce the risk of CNS toxicity. The hERG channel inhibition test was negative, indicating a low risk of cardiac toxicity in narcine cycline. The Ames test scored 0.6, indicating a low genotoxicity risk and meeting safety requirements.

Plant Origins and Extraction Methods

Narcissus spp. is mainly found in the bulbs and leaves of plants of the genus Narcissus and is one of the isoquinoline alkaloids unique to this genus. Daffodil plants are widely distributed across Europe, North Africa, and parts of Asia, and have traditionally been used for horticulture and medicinal purposes.

The process for extracting Narcissus cycline typically includes the following steps:

1. Raw material preparation: collect mature narcissus bulbs or leaves, dry them, and crush them into fine powder.
2. Solvent extraction: Extraction uses polar solvents such as methanol, ethanol, or ethyl acetate, with ultrasound-assisted extraction or reflux extraction to improve extraction efficiency.
3. Crude Extract Concentration: Concentrate the extract to an appropriate volume and remove most of the solvent.
4. Separation and purification: Separation and purification of narcissus cycline are performed using liquid-liquid separation, column chromatography (such as silica gel columns, C18 reversed-phase columns), and high-performance liquid chromatography (HPLC).
5. Structural identification: Confirm the structure using methods such as nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR).

In recent years, with advances in separation technology, supercritical fluid extraction and molecular blotting techniques have also been attempted for efficient extraction and purification of narcissus, significantly improving yield and purity.

Pharmacological activity research

Narcissianin exhibits significant pharmacological effects across various biological activities, especially in the antitumor field.

Antitumor activity

Narcissian exerts anti-tumor effects through multiple targets and pathways, covering various tumor cell lines including breast cancer, lung cancer, liver cancer, colorectal cancer, and brain tumors. Its main manifestations are:

• Inhibition of tumor cell proliferation: Narcissandin can induce tumor cell cycle arrest, slowing down the rate of cell proliferation.
• Promoting apoptosis: By regulating the expression of BCL2 family proteins (such as MCL1 and BCL2), mitochondrial pathways are activated to induce apoptosis.
• Inhibiting tumor invasion and metastasis: By downregulating the expression of matrix metalloproteinase MMP2, tumor cells reduce their ability to migrate and invade.
• Anti-angiogenesis: Inhibits HIF1A-mediated angiogenesis signals, blocking tumor nutrient supply.
• Regulatory signaling pathways: Inhibits STAT3, MAPK1, and other signaling pathways, blocking tumor cell survival and proliferation signals.

Other biological activities

Besides anti-tumor effects, Narcissandin acts as a plant growth regulator, significantly enhancing GTPase RhoA activity by regulating the Rho/Rho kinase/LIM kinase/cofilin signaling pathways, promoting actin stress fiber formation, and affecting cytoskeleton remodeling and cell motility. This mechanism is not only significant for regulating plant cell growth but also provides a molecular basis for its role in tumor cell migration and invasion.

Mechanism of action and molecular targets

The anti-tumor mechanisms of Narcissian are complex and diverse, mainly achieved through the following key targets and signaling pathways:

1. RhoA signal path regulation

Narcissus cycline significantly activates RhoA GTPase, which in turn activates downstream Rho kinase (ROCK) and LIM kinase (LIMK), regulating the phosphorylation state of actin-binding protein cofilin and promoting the formation of actin stress fibers. This process affects cell morphology and motility, inhibiting the migration and invasion of tumor cells.

2. Regulation of anti-apoptotic proteins

Narcissipcon downregulates the expression of anti-apoptotic proteins such as MCL1 and BCL2, disrupts mitochondrial membrane potentials, promotes the generation of intracellular reactive oxygen species (ROS), and activates apoptosis signaling pathways.

3. Signal transduction pathway suppression

• STAT3 inhibition: Narcissipin inhibits STAT3 phosphorylation and nuclear translocation, blocking its transcriptional activity and reducing tumor cell proliferation and survival.
• MAPK1 regulation: By modulating MAPK1 signaling, it influences the cell cycle and apoptosis processes.
• HIF1A inhibition: Reduces tumor hypoxia response, inhibits angiogenesis and tumor growth.
• TOP1 and TOP2A inhibition: interferes with DNA topoisomerase activity, blocks DNA replication and transcription, leading to tumor cell death.

4. Other targets

Narcissandin also affects estrogen receptors (ESR1) and aromatase (CYP19A1), suggesting its potential application value in hormone-dependent tumors such as breast cancer.

Druggability evaluation and pharmacokinetics

Druggability parameters

The molecular weight of Narcissusian cycline is 307.2580, meeting the molecular weight requirements of the Lipinski rule. Its LogP value is -0.4825, indicating good water solubility, but lower lipid solubility may limit its cell membrane permeability. The TPSA value is 128.48 Ų, and the higher polarity may affect oral absorption and bioavailability. Narcissiptracycline does not inhibit hERG channels, reducing the risk of cardiotoxicity. Ames test results show a low genotoxicity risk and good safety.

Pharmacokinetic characteristics

Currently, pharmacokinetic research on Narcissus cycline is relatively limited. Previous studies have shown that the oral bioavailability of Narcissus cycline is relatively low, mainly due to its high polarity and pronounced first-pass effect. Its low blood-brain barrier permeability limits its application in central nervous system tumors. Metabolism in the body mainly occurs through the liver enzyme system, and the metabolites still require further identification.

To enhance the pharmacokinetics of Narcissus, researchers have attempted strategies such as nanocarriers, liposome encapsulation, and structural modification to improve its in vivo stability and targeting properties, thereby enhancing its antitumor effect.

Prospects and outlooks for clinical applications

As a multi-target antitumor natural product, Narcissandanine has broad clinical development potential. Its unique mechanism of action enables it to show good inhibitory effects across various tumor types, especially showing advantages in refractory and drug-resistant tumors.

Future research directions include:

• Preclinical safety evaluation: Systematic evaluation of the toxicological characteristics and long-term safety of Narcissusin.
• Drug delivery system development: Utilizing nanotechnology and targeted delivery strategies to improve in vivo stability and tumor targeting.
• Structural optimization and derivative development: Chemical modification improves its pharmacokinetic properties and biological activity.
• Combination drug research: exploring combined use with chemotherapy drugs and immune checkpoint inhibitors to enhance anti-tumor effects.
• Clinical trial design: Promote Narcissandin's entry into clinical trials to verify its safety and efficacy.

Moreover, research on Narcissus cycline in plant growth regulation and cytoskeletal regulation has provided new ideas for its applications in agriculture and cell biology.

Conclusion

As a natural product with a unique structure and multi-target mechanism, Narcissandin-Cycline demonstrates significant anti-tumor potential. By regulating the RhoA signaling pathway and various key regulatory factors, it inhibits tumor cell proliferation, migration, and angiogenesis, promoting tumor cell apoptosis. Although its druggability remains challenging, through modern drug delivery technology and structural optimization, Narcine cycline is expected to become an important candidate for the new generation of anti-tumor drugs. In the future, in-depth mechanistic research and clinical development will further advance the drug development of Narcinocycline, bringing new hope to cancer treatment.