Synonym name:
Catalogue No.: BP0528
Cas No.: 519-23-3
Formula: C₁₇H₁₄N₂
Mol Weight: 246.313
Botanical Source: Alkaloid from Ochrosia elliptica, Ochrosia moorei and several other Ochrosia spp., Senecio sp., Strychnos dinklagei, Aspidosperma subincanum,

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

Ellipticine (CAS No.: 519-23-3) is an organic heterotetracyclic alkaloid derived from plants, attracting significant attention in pharmacology and natural product chemistry due to its remarkable antitumor activity. Roseordin, first isolated from plants in the Apocynaceae family, has become an important candidate compound for anticancer drug development due to its unique chemical structure and multi-target mechanism. As a pyridine-[4,3-b]carbazole compound, rosushine not only inhibits DNA topoisomerase II but also exhibits various cytotoxic effects, particularly showing significant growth inhibition in various tumor cell lines. This paper will systematically review the chemical structure, plant origin, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects of rosalin, aiming to provide theoretical basis and reference for in-depth research and drug development of this natural product.

Chemical structure and physicochemical properties

Rose alkaloid is an organic nitrogen heterocyclic compound with a molecular formula of C17H14N2 and a molecular weight of 246.31. Its structural feature is a pyridine-b[4,3-b]carbazole backbone, with two methyl substituents at positions 5 and 11, belonging to the polycyclic heteroaromatic hydrocarbon and indole alkaloid compounds. This structure gives it a unique planar rigid conformation, which facilitates insertion binding with DNA molecules, thereby interfering with the normal function of DNA.

In terms of physicochemical properties, rosine has a LogP value of 2.8, indicating moderate lipid solubility, which facilitates cell membrane penetration. Its topological pole surface area (TPSA) is 38.88 Ų, and it has 2 hydrogen bond acceptors, suggesting that it possesses certain affinity for binding to biomacromolecules. Rosephylline has a high blood-brain barrier penetration (BBB high permeability), which offers potential applications in the treatment of central nervous system tumors. However, it carries relatively high risks of hepatotoxicity and cardiotoxicity, and it shows hERG channel inhibitory activity and positive Ames tests, suggesting potential genotoxicity and cardiac safety concerns, which require special attention during drug development.

Plant Origins and Extraction Methods

Rosethering alkali was originally isolated from plants of the genus Apocynaceae, especially the roots and leaves of plants in the genus Elliptica. These plants are widely distributed in tropical and subtropical regions and have traditionally been used in folk herbal medicine to treat various diseases.

The extraction methods mainly include organic solvent extraction extraction, column chromatography separation, and high-performance liquid chromatography (HPLC) purification. Common extraction solvents include methanol, ethanol, or ethyl acetate. After crude extraction, silica gel column chromatography is used for separation, purity is monitored by thin-layer chromatography (TLC), and high-purity rosalkaloid is ultimately obtained by HPLC. In recent years, supercritical CO2 extraction technology and microwave-assisted extraction methods have also been applied to improve extraction efficiency and purity, reduce the use of organic solvents, and align with green chemistry principles.

Pharmacological activity research

The pharmacological activity of rosaline is mainly reflected in its antitumor effects. Multiple in vitro and in vivo studies have shown that rosushidine has significant cytotoxic and growth-inhibiting effects on various tumor cell lines (such as breast cancer, lung cancer, leukemia, brain tumors, etc.). Its IC50 value typically ranges from nanomoles to micromoles, showing strong pharmacodynamic activity.

In addition, rosalin also exhibits certain antibacterial, anti-inflammatory, and antioxidant activities, but research on these non-tumor-related effects is relatively limited and requires further exploration. It is worth noting that the efficacy of rosalophyrrine in vivo is limited by its metabolic stability and toxic side effects, especially in the liver and heart, which restrict its broad clinical application.

Mechanism of action and molecular targets

The antitumor mechanism of rosushicine is mainly realized through the following aspects:

1. DNA topoisomerase II inhibition
   Rose alkaloid can insert and bind to DNA double helix structures, blocking the activity of DNA topoisomerase II, leading to DNA strand breaks and replication disorders. This mechanism severely disrupts tumor cells during DNA replication and division, inducing cell cycle stagnation and apoptosis.

2. Induces apoptosis
   By activating endogenous apoptosis pathways, rosushidine promotes mitochondrial membrane potential loss, cytochrome C release, and caspase cascade activation, ultimately leading to programmed death of tumor cells.

3. Regulation of oxidative stress
   Rose alkaloids can cause increased intracellular reactive oxygen species (ROS) levels, disrupt cellular redox balance, and promote oxidative stress-mediated cell damage and apoptosis.

4. Affects cell signaling pathways
   Research shows that rosine can regulate multiple key cellular signaling pathways, such as PI3K/Akt, MAPK, and NF-κB pathways, further inhibiting tumor cell proliferation and migration.

5. Multi-target action
   In addition to DNA topoisomerase II, rosushicine may also act on other molecular targets, such as DNA methyltransferase and epigenetic regulatory factors, exhibiting complex multi-target anti-cancer properties.

Druggability evaluation and pharmacokinetics

The druggability evaluation of rosamine shows it has certain advantages but also significant challenges. It has a moderate molecular weight and good lipid solubility, effectively penetrating cell membranes and the blood-brain barrier, making it suitable for treating brain tumors. However, its hepatotoxicity and cardiotoxicity, especially its inhibitory effects on the hERG channel, increase the risk of potential arrhythmias and limit the increase in safe doses.

Pharmacokinetic studies show that rosalin is metabolized rapidly in the body, mainly through the hepatic CYP450 enzyme system, and its metabolites may have different activities and toxicity. Its bioavailability is limited by the first-pass effect and is widely distributed in the body, especially at higher concentrations in brain tissue. To improve its pharmacokinetic properties, researchers have tried to enhance its stability and targeting by using drug carrier systems (such as liposomes and nanoparticles) and structural modification strategies to reduce toxic side effects.

Additionally, positive Ames test results for rosushidine suggest potential genotoxicity risks and require focused monitoring during preclinical safety evaluations.

Prospects and outlooks for clinical applications

Although rosushicine exhibits excellent antitumor activity, its clinical application still faces many challenges. Currently, rosalin has not yet received broad clinical approval, mainly due to its toxicity risks and pharmacokinetic limitations. Future research directions include:

1. Toxicity mitigation strategies
   By optimizing drug structure, improving dosage forms, and combining drugs, liver and cardiac toxicity is reduced and safety is enhanced.

2. Targeted drug delivery systems
   By utilizing nanotechnology, antibody-drug conjugates (ADCs), and other methods, precise targeted delivery to tumor tissues can be achieved, reducing damage to normal tissues.

3. Combination therapy
   Combined with other anticancer drugs, radiotherapy, or immunotherapy, it exerts synergistic effects, enhances treatment outcomes, and reduces the incidence of drug resistance.

4. Central nervous system tumor treatment
   Due to its high blood-brain barrier penetration ability, rosrosetine has potential for further exploration in the treatment of central nervous system malignancies such as brain tumors.

5. Development of new derivatives
   Novel derivatives are designed and synthesized based on the rosalkaloid framework to optimize efficacy and safety, expanding their indications.

In summary, rosushidine, as a natural antitumor agent, has broad research and application prospects, but it still needs to overcome bottlenecks in toxicity and pharmacokinetics to promote clinical translation.

Conclusion

Rosalin, a natural product with a unique chemical structure and multi-target anti-tumor mechanism, demonstrates significant anti-cancer potential. By inhibiting DNA topoisomerase II, inducing apoptosis, and regulating multiple signaling pathways, it effectively kills tumor cells. However, risks of hepatotoxicity, cardiotoxicity, and genotoxicity limit its clinical application. In the future, combining modern drug design with nanotechnology to optimize the pharmacokinetics and safety of rosalin will be key to achieving its clinical translation. Ongoing basic and applied research will provide solid scientific support for the development of rosogenic anti-tumor drugs, driving it to become an important drug in the field of cancer treatment.