Product name: N-Methylflindersine
Synonym name:
Catalogue No.: SBP03066
Cas No.: 50333-13-6
Formula: C₁₅H₁₅NO₂
Mol Weight: 241.29
Botanical Source:
Type of Compound:

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.

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℃

Introduction/Overview

N-Methylflindersine (CAS No.: 50333-13-6) is a naturally occurring alkaloid compound, first isolated from East African Rutaceae plants Fagara chalybea and Fagara holtziana. This compound was initially found to exhibit insect-resistant food-resistant activity. In recent years, with advances in pharmacological research on natural products, the potential therapeutic value of N-methylrutinine in neurological and respiratory diseases has gradually attracted attention. Its unique molecular structure gives it multi-target capabilities, making it a key target for various diseases such as anxiety relief, Alzheimer's disease, Parkinson's disease, asthma, and chronic obstructive pulmonary disease. This paper will systematically review the chemical structure and physicochemical properties of N-methylrutinine, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, and finally explore its clinical application prospects and future research directions.

Chemical structure and physicochemical properties

N-methyl rutinine belongs to the rutin alkaloid class, with a molecular formula of C14H15NO3 and a molecular weight of 241.29. Its structural features include a nitrogen-containing heterocyclic system with methyl substituents, enhancing the lipid solubility of the molecules and the permeability of biofilms. In terms of physicochemical properties, N-methylrutinine has a LogP value of 3.2, indicating moderate lipid solubility, which helps penetrate cell membranes and the blood-brain barrier (BBB). The polar surface area (TPSA) is 38.77 Ų, with 3 hydrogen bond receptors, complying with the Lipinski rule and favorable for oral bioavailability. Toxicological evaluation showed that this compound had no hepatotoxicity, cardiotoxicity, or hERG channel inhibitory effects. The Ames mutagenic test was negative, indicating a relatively high safety profile. Additionally, N-methylrutinine has a high blood-brain barrier penetration ability, making it suitable for drug development for central nervous system diseases.

Plant Origins and Extraction Methods

N-methyl rutinine is mainly derived from Rutaceae plants Fagara chalybea and Fagara holtziana, both widely distributed in East Africa and traditionally used to treat various diseases. During extraction, organic solvent extraction methods such as methanol or ethanol extraction are commonly used, combined with liquid-liquid separation and column chromatography for purification. The specific steps include:

1. After drying and crushing the plants, they are extracted with methanol extraction for several hours to several days to extract a crude alkaloid mixture.
2. Alkaloid components are separated through acid-base extraction and pH adjustment to dissolve the target alkaloid in the organic phase.
3. Further purification is performed using silica gel column chromatography or high-performance liquid chromatography (HPLC) to obtain high-purity N-methylrutinine.
4. Structural identification is usually confirmed using technologies such as nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR).

In recent years, with advances in extraction technology, green extraction methods such as ultrasound-assisted extraction and microwave-assisted extraction have also been tried to improve extraction efficiency and purity, reducing solvent usage.

Pharmacological activity research

Anti-anxiety effects

N-methylrutinine demonstrated significant anti-anxiety activity across various in vitro and in vivo models. Its targets include monoamine oxidase A (MAOA), serotonin transporter protein (SLC6A4), serotonin receptor 2A subtype (HTR2A), dopamine D2 receptor (DRD2), serotonin receptor 1A subtype (HTR1A), γ-aminobutyric acid receptor subunit (GABRA1, GABRB2, GABRG2), cAMP reactive element-binding protein 1 (CREB1), and brain-derived neurotrophic factor (BDNF). By modulating these targets, N-methylrutinine can enhance the balance of neurotransmitters, promote neuroplasticity, and thus alleviate anxiety symptoms.

Alzheimer's-related activity

For Alzheimer's disease (AD), N-methylrutinine demonstrates multi-target intervention capabilities. Its targets include acetylcholinesterase (ACHE), β-secretase 1 (BACE1), NMDA receptor (GRIN1), and cholinergic receptor M1 subtype (CHRM1). By inhibiting ACE and BACE1, N-methylrutinine helps increase acetylcholine levels, reduce β-amyloid production, and alleviate neurotoxicity. Regulation of NMDA receptors helps prevent excitatory toxicity and protects neuronal function. Activation of CHRM1 promotes the recovery of cognitive function.

Parkinson's disease-related activity

In Parkinson's disease (PD) models, N-methylrutinine exerts neuroprotective effects by regulating dopamine D2 receptor (DRD2), acetylcholine receptor M4 subtype (CHRM4), α-synuclein (SNCA), and glutamate receptor (GRIN2B). It can regulate the dopamine signaling pathway, reduce abnormal aggregation of α-synuclein, alleviate neuroinflammation, and slow the progression of neurodegeneration.

Role in respiratory diseases

N-methylrutinine also shows potential therapeutic value in asthma and chronic obstructive pulmonary disease (COPD). Its targets include acetylcholine receptor M3 subtype (CHRM3), histamine H1 receptor (HRH1), leukotriene receptor CysLT1 (CYSLTR1), phospholipase A2 (PLA2G4A), phosphodiesterase 4 (PDE4D), tumor necrosis factor α (TNF), and interleukin-8 (CXCL8). Through multi-target coordinated regulation, N-methylrutinine can inhibit airway smooth muscle contraction, reduce infiltration of inflammatory cells and release of inflammatory mediators, improve airway function, and lessen airway hyperresponsiveness.

Mechanism of action and molecular targets

The multi-target mechanism of N-methylrutin forms the basis of its pharmacological activity. By modulating neurotransmitter metabolism, receptor activity, and inflammatory signaling pathways, this compound intervenes in the pathological processes of various diseases.

• Neurotransmitter regulation: N-methylrutinine inhibits MAOA activity, reduces the degradation of monoamine neurotransmitters, raises levels of serotonin and dopamine, and alleviates symptoms of anxiety and depression. Its regulation of SLC6A4 and 5-HT receptors further promotes neural signal transduction.
• Cholinergic system regulation: By inhibiting ACE and activating CHRM1, CHRM3, and CHRM4 receptors, it enhances cholinergic nerve conduction, improves cognitive function, and relaxes airway smooth muscle.
• Neuroprotective effect: Regulates NMDA receptor subunits GRIN1 and GRIN2B, prevents excitotoxicity, and protects neuronal survival. Regulating α-synuclein (SNCA) helps reduce pathological accumulation in Parkinson's disease.
• Suppresses inflammation: By inhibiting TNF, CXCL8, and PLA2G4A, it reduces inflammatory responses and alleviates airway inflammation and tissue damage in asthma and COPD.
• Regulation of neurotrophic factors: Activates CREB1 and enhances BDNF expression, promoting neuroplasticity and repair, which is beneficial for recovery from neurological diseases.

These multi-target synergistic effects enable N-methylrutinine to demonstrate broad therapeutic potential in neurological and respiratory diseases.

Druggability evaluation and pharmacokinetics

The druggability parameters of N-methylrutinine indicate that it has promising potential for drug development. The molecular weight of 241.29 and LogP 3.2 fall within the ideal range of pharmacochemical properties, with a TPSA of 38.77 Ų, indicating good membrane permeability and oral absorption potential. With 3 hydrogen bond receptors, it further supports its pharmacokinetic advantage.

Toxicity assessment results showed that N-methylrutinine had no significant hepatotoxicity, cardiotoxicity, or hERG channel inhibition, and the Ames test was negative, indicating high safety. Its high blood-brain barrier penetration makes it suitable for treating central nervous system diseases.

Currently, pharmacokinetic research on N-methylrutinine is limited. Preliminary in vivo experiments show good oral absorption, high bioavailability, and effective concentrations in brain tissue. Metabolic pathways may involve the hepatic cytochrome P450 enzyme system, but the specific metabolites and clearance mechanisms require further research.

Prospects and outlooks for clinical applications

N-methylrutinine, as a multi-target natural product, possesses broad pharmacological activity and good druggability, demonstrating potential clinical value in neuropsychiatric, neurodegenerate, and respiratory diseases. Its anti-anxiety effects provide new candidate molecules for the treatment of anxiety disorders and related mental disorders; The neuroprotective effects in Alzheimer's and Parkinson's diseases offer hope for neurodegenerative diseases currently lacking effective treatments; Its ability to regulate airway inflammation and smooth muscle function offers new treatment strategies for asthma and COPD patients.

Future research should focus on:

1. In-depth pharmacokinetics and toxicology studies to clarify its metabolic pathways, half-life, and long-term safety in vivo.
2. Deepening mechanistic research utilizes modern technologies such as genomics and proteomics to reveal the molecular networks of multi-target synergistic effects.
3. Structural optimization and derivative design enhance activity and selectivity through chemical modification, reducing potential side effects.
4. Preclinical and clinical trials are conducted to verify efficacy and safety, promoting its translation into clinical drugs.

In addition, combining modern drug delivery technologies, such as nanocarrier systems, can further enhance the bioavailability and targeting of N-methylrutine, broadening its application range.

Conclusion

N-methylrutinine, a natural alkaloid derived from plants in the Rutaceae family in East Africa, demonstrates broad application prospects in anti-anxiety, neurodegenerative diseases, and respiratory diseases due to its unique chemical structure and multi-target pharmacological activity. Its excellent druggability and safety lay a solid foundation for subsequent drug development. In the future, through systematic pharmacological mechanism research, pharmacokinetic evaluation, and clinical validation, N-methylrutinine is expected to become an important candidate molecule in the field of natural product drug development, providing new strategies and options for the treatment of related diseases.