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℃
Ellipticine (CAS number: 519-23-3) is an organic heterocyclic alkaloid derived from plants, which has attracted much attention in the fields of pharmacology and natural product chemistry due to its significant anti-tumor activity. The rose bark alkaloid, which was first isolated from Apocynaceae plants, has become an important candidate compound for anti-cancer drug development due to its unique chemical structure and multi-target mechanism of action. As a pyrido [4,3-b] carbazole compound, rosepine alkaloid not only has the activity of inhibiting DNA topoisomerase II, but also exhibits various cytotoxic effects, especially significant growth inhibitory effects in various tumor cell lines. This article will provide a systematic review of the chemical structure, plant sources, pharmacological activities, mechanisms of action, pharmacological evaluation, and clinical application prospects of Rosaceae alkaloids, aiming to provide theoretical basis and reference for the in-depth research and drug development of this natural product.
Rose tree 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 pyrido [4,3-b] carbazole skeleton with two methyl substituents at positions 5 and 11, belonging to polycyclic aromatic hydrocarbons and indole alkaloids. This structure endows it with a unique planar rigid conformation, which facilitates insertion binding with DNA molecules, thereby interfering with the normal function of DNA.
In terms of physical and chemical properties, the LogP value of rose bark alkaloid is 2.8, indicating its moderate lipid solubility, which is beneficial for cell membrane penetration. Its topological polar surface area (TPSA) is 38.88 Å ² and the number of hydrogen bond acceptors is 2, indicating that it has a certain affinity when binding to biomolecules. Rosebark alkaloids have a high blood-brain barrier permeability (BBB high permeability), which provides the possibility for their potential application in the treatment of central nervous system tumors. However, it has a high risk of hepatotoxicity and cardiotoxicity, and exhibits hERG channel inhibitory activity and positive Ames test, indicating potential genetic toxicity and cardiac safety issues, which need to be given special attention in drug development.
Rosepine alkaloids were initially isolated from plants in the Apocynaceae family, particularly from the roots and leaves of plants in the Elliptica genus. This type of plant is widely distributed in tropical and subtropical regions and has traditionally been used in folk herbal medicine to treat various diseases.
The extraction methods mainly include organic solvent extraction, column chromatography separation, and high-performance liquid chromatography (HPLC) purification. The commonly used extraction solvents are methanol, ethanol, or ethyl acetate. After crude extraction, they are separated by silica gel column chromatography, and the purity is monitored by thin layer chromatography (TLC). Finally, high-purity rosealkaloids are 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 comply with green chemistry principles.
The pharmacological activity of rosepine alkaloids is mainly reflected in their anti-tumor effects. A number of in vitro and in vivo studies have shown that rosaniline has significant cytotoxicity and growth inhibition effects on a variety of tumor cell lines (such as breast cancer, lung cancer, leukemia, brain tumor, etc.). Its IC50 value is usually in the range of nanomoles to micromoles, demonstrating strong pharmacological activity.
In addition, Rosaceae also exhibits certain antibacterial, anti-inflammatory, and antioxidant activities, but there is relatively little research on these non tumor related effects, and further exploration is needed. It is worth noting that the pharmacological performance of rosmarine in vivo is limited by its metabolic stability and toxic side effects, especially the toxic reactions in the liver and heart, which limit its widespread clinical application.
The anti-tumor mechanism of Rosaceae alkaloids is mainly achieved through the following aspects:
Inhibition of DNA Topoisomerase II
Rosepine alkaloids can insert and bind to the double helix structure of DNA, blocking the activity of DNA topoisomerase II, leading to DNA strand breaks and replication disorders. This mechanism causes severe interference to tumor cells during DNA replication and division, inducing cell cycle arrest and apoptosis.
Inducing cell apoptosis
By activating the endogenous apoptotic pathway, Rosaine promotes mitochondrial membrane potential loss, cytochrome C release, and caspase cascade activation, ultimately leading to programmed cell death in tumor cells.
Oxidative stress regulation
Rosebark alkaloids can cause an increase in intracellular reactive oxygen species (ROS) levels, disrupt cellular redox balance, and promote oxidative stress-induced cell damage and apoptosis.
Affects cellular signaling pathways
Research has shown that rosepine alkaloids can regulate multiple key cellular signaling pathways, such as PI3K/Akt, MAPK, and NF - κ B pathways, further inhibiting the proliferation and migration of tumor cells.
Multi-target effect
In addition to DNA topoisomerase II, rosepine alkaloids may also act on other molecular targets, such as DNA methyltransferases and epigenetic regulatory factors, exhibiting complex multi-target anti-cancer properties.
The pharmacological evaluation of rose bark alkaloid shows that it has certain advantages and significant challenges. It has a moderate molecular weight, good lipid solubility, and can effectively penetrate cell membranes and the blood-brain barrier, making it suitable for treating brain tumors. However, its hepatotoxicity and cardiotoxicity, especially the hERG channel inhibitory effect, increase the potential risk of arrhythmia and limit the safe dose increase.
Pharmacokinetic studies have shown that rosmarine is rapidly metabolized in vivo, mainly through the CYP450 enzyme system in the liver, and the 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 high concentrations in brain tissue. To improve its pharmacokinetic properties, researchers have attempted to enhance its stability and targeting, and reduce toxic side effects through drug carrier systems (such as liposomes, nanoparticles) and structural modification strategies.
In addition, the positive Ames test results of Rosepine alkaloids suggest a potential genetic toxicity risk and need to be closely monitored in preclinical safety evaluations.
Despite exhibiting excellent anti-tumor activity, the clinical application of rosepine alkaloids still faces many challenges. Currently, rosepine alkaloids have not received widespread clinical approval, mainly due to their toxicity risks and pharmacokinetic limitations. Future research directions include:
Toxicity mitigation strategy
By optimizing drug structure, improving dosage forms, and using combination therapy, liver and cardiac toxicity can be reduced, and safety can be improved.
Targeted drug delivery system
By utilizing nanotechnology, antibody drug conjugates (ADCs), and other techniques, precise targeted delivery to tumor tissues can be achieved, reducing damage to normal tissues.
Combination therapy
Combining with other anti-cancer drugs, radiotherapy, or immunotherapy to achieve synergistic effects, improve treatment efficacy, and reduce the occurrence of drug resistance.
Treatment of central nervous system tumors
Due to its high blood-brain barrier penetration ability, the potential of rose alkaloids in the treatment of central nervous system malignancies such as brain tumors is worth further exploration.
Development of new derivatives
Design and synthesize novel derivatives based on the rose tree alkaloid skeleton, optimize their efficacy and safety, and expand their indications.
In summary, as a natural anti-tumor agent, Rosaceae has broad research and application prospects, but it still needs to overcome the bottlenecks of toxicity and pharmacokinetics to promote its clinical translation.
Rose tree alkaloids, as a natural product with unique chemical structure and multi-target anti-tumor mechanism, exhibit significant anti-cancer potential. It achieves effective killing of tumor cells by inhibiting DNA topoisomerase II, inducing cell apoptosis, and regulating multiple signaling pathways. However, the risks of liver toxicity, cardiac toxicity, and genetic toxicity limit its clinical application. In the future, combining modern drug design and nanotechnology to optimize the pharmacokinetics and safety of rosuvastatin is the key to achieving its clinical translation. Continuous basic and applied research will provide solid scientific support for the development of rose bark alkaloids as anti-tumor drugs, promoting them to become important drugs in the field of cancer treatment.
