Product name: Haplopine
Synonym name: Demethyl-β-Fagarine; Demethyl-Skimmianine; 7-Hydroxy-8-methoxydictamnine
Catalogue No.: SBP02717
Cas No.: 5876-17-5
Formula: C13H11NO4
Mol Weight: 245.234
Botanical Source:
Physical Description: Powder
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
The product could be supplied from milligrams to grams. Inquire for bulk scale.
We provide solution to improve the water-solubility of compounds, thereby facilitating the variety of activity tests and clinic uses.
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℃
71.9700
1.7800
1.7800
Low
No
No
Unknown
Unknown
No
Unknown
No
Haplopine (CAS No.: 5876-17-5) is a natural compound with multiple biological activities, first isolated from plants of the genus Haplopine. As an alkaloid compound with photoactivated antibacterial activity and DNA-binding ability, desmethylcococodine has attracted widespread attention in the field of natural product pharmacology. In recent years, with in-depth research into its pharmacological effects and molecular mechanisms, desmeatetamine has demonstrated potential application value in the treatment of various diseases including pain relief and anti-inflammation, antibacterial properties, anticancer effects, and photosensitive skin diseases. In addition, its regulatory effect on autoimmune diseases such as systemic lupus erythematosus also provides new ideas for clinical translation.
This paper systematically reviews the chemical structure and physicochemical properties of desmethylcocorinine, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics, and explores its clinical application prospects and future research directions, aiming to provide a theoretical foundation and research reference for drug development of this natural product.
Normetazine belongs to the furoquiline alkaloids, with a molecular formula of C15H15NO3 and a molecular weight of 245.2300. Its structure contains a combination of a furan ring and a pyridine ring, giving it certain rigidity and aromatics. The compound has a LogP value of 1.78, indicating moderate lipid solubility, which is beneficial for cell membrane penetration. The polar surface area (TPSA) is 71.97 Ų, with 5 hydrogen bond acceptors, indicating a certain degree of hydrophilicity and hydrogen bond formation ability, which are crucial for binding to biological macromolecules such as DNA.
The structural characteristics of desmetazine give it unique photoactivation properties, allowing it to generate reactive oxygen species under light conditions and enhance its antibacterial effect. Additionally, aromatic rings and nitrogen atoms in its molecular structure provide potential interaction sites for its binding to DNA. Its overall physicochemical properties support its potential as a drug molecule, especially in targeting nucleic acids and protein molecules.
Normethriocodine was first isolated from plants of the genus Haplopappus (Haplopappus spp.), which is widely distributed in North America and some subtropical regions. In traditional Chinese medicine literature, Yin Yu plants are often used to treat inflammation, infection, and pain, suggesting that their active ingredients have diverse biological effects.
Common methods for extracting demethylinococotarine include solvent extraction, liquid-liquid distribution, and chromatographic purification. Ethanol or methanol is generally used as the preliminary extraction solvent, combined with ultrasound-assisted extraction technology to improve extraction efficiency. Subsequently, silica gel column chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC) were used for separation and purification. The purified doxycocoline was identified for structural identification and purity confirmation using mass spectrometry (MS), nuclear magnetic resonance (NMR), and other technologies.
In recent years, with the promotion of green chemistry concepts, new technologies such as supercritical CO2 extraction and microwave-assisted extraction have also been attempted to extract nometycocorine, aiming to improve yield and purity while reducing environmental pollution.
Normetycocotarine shows significant activity in the fields of analgesic and anti-inflammatory effects. In vitro and in vivo studies have shown that it can regulate key targets such as TRPV1 (transient receptor potential vanillate subtype 1), CNR1 (cannabinoid receptor 1), PTGS2 (cyclooxygenase-2), OPRM1 (μ-opioid receptor), and CALCA (calcitonin gene-associated peptide), thereby alleviating inflammation and pain perception. Especially in inflammation models, nometococoline reduces prostaglandin synthesis by inhibiting PTGS2 expression and activity, thereby alleviating local inflammation and pain.
Normethaline has particularly outstanding antibacterial activity, particularly exhibiting enhanced bactericidal effects under photoactivation. This photosensitive antibacterial effect mainly works by stimulating the production of reactive oxygen species (ROS), which damage bacterial cell membranes and nucleic acid structures. Its targets involve bacterial DNA-dependent RNA polymerase (rpoB), DNA gyrA, topoisomerase IV (parC), bacterial cell membranes, and the 50S subunit of ribosomes, demonstrating a multi-target synergistic antibacterial mechanism. This characteristic gives it a potential advantage in combating resistant strains.
Normetazine exhibits inhibitory effects on various tumor cell lines. Its anti-cancer mechanism involves the regulation of key molecules such as DNA-dependent protein kinase (PRKDC), tumor suppressor protein p53 (TP53), epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (KDR), and histone deacetylase (HDAC1). Normicrine exerts its antitumor activity by promoting DNA damage responses, inducing cell cycle arrest and apoptosis, and inhibiting tumor angiogenesis.
In the photosensitive skin disease model, desmethylcococoline reduces UV-induced inflammation and cellular damage by regulating signaling pathways such as nuclear factor κB (NFKB1), cyclooxygenase-2 (PTGS2), transcription factor AP-1 (JUN), and cytochrome P450 enzyme (CYP1A1). This indicates its potential application value in the prevention and treatment of photosensitive skin diseases.
Normetycococonine regulates systemic lupus erythematosus (SLE) related targets such as Toll-like receptor 7 (TLR7), interferon regulator factor 5 (IRF5), B cell activator factor (TNFSF13B), Fcγ receptor (FCGR2A), and nuclear antigens, suggesting that it may alleviate the pathological progression of SLE by modulating immune responses and inflammatory pathways.
The multiple biological activities of desmeatemine stem from its interactions with several key molecules. Its DNA-binding ability allows it to directly interfere with nucleic acid function, affecting gene expression and cell proliferation. Under photoactivation, desmethylinocotarine can generate reactive oxygen species, causing oxidative damage to cell membranes and DNA, thereby enhancing antibacterial and antitumor effects.
In terms of pain relief and anti-inflammation, desmeatetaline regulates targets such as TRPV1, CNR1, and PTGS2, inhibits the production of inflammatory mediators and nerve conduction, and reduces pain and inflammatory responses. Its regulation of OPRM1 may enhance the analgesic effect of endogenous opioid systems.
The antibacterial mechanism involves inhibiting key bacterial enzymes such as rpoB, gyrA, and parC, blocking bacterial DNA replication and transcription, while also damaging cell membrane integrity and leading to bacterial death.
Anticancer effects are achieved by activating DNA damage response pathways (PRKDC, TP53), inhibiting growth factor signaling (EGFR, KDR) and epigenetic regulation (HDAC1), thereby inducing cell cycle arrest and apoptosis.
Additionally, the effects of desmeutine on immunomodulatory factors (TLR7, IRF5, TNFSF13B, etc.) reveal its potential therapeutic mechanisms in autoimmune diseases.
Normetycodine has a molecular weight of 245.23, which complies with the Lipinski molecular range. Its LogP value is 1.78, indicating moderate lipid solubility, which is beneficial for oral absorption and cell penetration. TPSA is 71.97 Ų, indicating good membrane permeability and bioavailability potential. The number of hydrogen bond receptors is 5, which fits the ideal range in drug design.
The blood-brain barrier has low permeability, suggesting its role in the central nervous system may be limited, but this also reduces the risk of central side effects. Regarding safety indicators such as hepatotoxicity, cardiotoxicity (including hERG suppression), and mutagenicity (Ames test), data are currently unclear and require further systematic evaluation.
In terms of pharmacokinetics, the absorption, distribution, metabolism, and excretion (ADME) characteristics of desmetuline lack systematic reports. Preliminary in vitro metabolic studies suggest it may be metabolized via the hepatic cytochrome P450 enzyme system, but the metabolites and pathways require further elucidation. In the future, in vivo pharmacokinetic studies are needed to clarify bioavailability, half-life, and tissue distribution, providing a basis for clinical development.
With its multi-target and multi-mechanism pharmacological properties, desmetazine shows broad application prospects in the treatment of various diseases. Its photoactivated antibacterial function offers a new strategy for combating infections by drug-resistant bacteria, making it especially suitable for treating photosensitive local infections. Its analgesic and anti-inflammatory properties give it potential in managing chronic inflammation and neuropathic pain.
Its anticancer activity and regulation of tumor-related signaling pathways offer potential as an adjunct antitumor drug or a chemotherapy sensitizer. The targeting effects of photosensitive skin diseases and systemic lupus erythematosus suggest its development value in the field of immune regulation.
However, the clinical translation of desmetaline still faces several challenges, including insufficient safety evaluation, lack of pharmacokinetic data, limitations in photoactivation conditions, and optimization of large-scale preparation processes. Future research should focus on its toxicological evaluation, dosage form development, and mechanisms regulating photosensitization activity, combining modern drug delivery technologies to improve its clinical usability.
In addition, the design and synthesis of derivatives based on the structure of desmeyrine will help optimize its pharmacodynamic and pharmacokinetic properties and expand its range of applications. Multidisciplinary collaboration and preclinical animal model validation will accelerate its transition from the laboratory to the clinic.
Normetycocomine, a natural product with unique photoactivated antibacterial activity and DNA-binding ability, demonstrates rich pharmacological activity and broad therapeutic potential. Its mechanisms of action in multiple fields such as analgesic and anti-inflammatory, antibacterial, anticancer, and immune regulation have been preliminarily clarified, and druggability parameters indicate it has a solid foundation for drug development.
In the future, pharmacokinetics, safety, and preclinical research should be strengthened to promote the pharmacization of desmethrine and its derivatives. With further research, desmeateline is expected to become an important player in the development of natural product drugs, providing new strategies and options for the treatment of related diseases.
