Synonym name: Caulophylline
Catalogue No.: BP0999
Cas No.: 486-86-2
Formula: C12H16N2O
Mol Weight: 204.273
Botanical Source: Alkaloid from Cytisus laburnum, Genista spp., Leontice spp., Spartium junceum and very many other spp. and genera in the Leguminosae
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℃
N-Methylcytidine (CAS number: 486-86-2) is an important tricyclic quinoline alkaloid that has attracted much attention due to its unique chemical structure and diverse pharmacological activities. As a natural product, N-methyl quercetin has a long history of application in traditional Chinese medicine. Modern pharmacological studies have shown that it has significant hypoglycemic, pain relieving, and anti-inflammatory effects, and exhibits highly selective affinity for acetylcholine nicotinic receptors (nAChRs) in the central nervous system. In addition, N-methylquercetin has shown potential drug development value in the field of anti malaria, with related targets covering multiple key proteins of malaria parasites. This article aims to systematically review the chemical structure and physicochemical properties, plant sources and extraction methods, pharmacological activity and mechanism of action, pharmacological evaluation and pharmacokinetic characteristics of N-methyl quercetin, and explore its clinical application prospects and future research directions.
N-Methylquercetin belongs to the tricyclic quinoline alkaloids, with a molecular formula of C11H14N2O and a molecular weight of 204.2730. Its core structure consists of a tricyclic system with a methylated nitrogen atom, endowing it with unique chemical properties and biological activity. In terms of physicochemical properties, the LogP value of N-methylquercetin is 0.3319, indicating its moderate lipophilicity, which facilitates cell membrane penetration and blood-brain barrier (BBB) penetration, consistent with its high BBB permeability. The polar surface area (TPSA) is 25.2400, indicating that the molecular polarity is low and beneficial for targeting the central nervous system. The water solubility is 46.4068, indicating its moderate solubility in water, which is beneficial for absorption and distribution in the body. In the toxicological evaluation, N-methyl quercetin did not exhibit hERG channel inhibition, and the Ames test result was 0.0, indicating a low genetic toxicity risk and good safety.
N-Methylquercetin is mainly found in various traditional Chinese medicinal plants, especially in plants of the Passeriformes family such as Fundulopalpus spp. and Caulophyllum spp., which are abundant in content. It has a wide range of natural sources and is commonly found in roots, stems, and leaves. Traditional extraction methods often use alcohol solvents (such as ethanol and methanol) for extraction, combined with acid-base regulation to promote the release of alkaloids. Modern extraction techniques introduce ultrasound assisted extraction, microwave-assisted extraction, and high-performance liquid chromatography (HPLC) separation and purification techniques to improve extraction efficiency and purity. The typical process includes: drying and crushing of plant materials, extraction with 70% ethanol, concentration of filtrate, acid-base adjustment to convert alkaloids into free state, followed by liquid-liquid extraction or column chromatography for separation, and finally purification by HPLC to obtain high-purity N-methyl quercetin.
N-Methylquercetin has shown significant hypoglycemic effects in multiple in vitro and in vivo experiments. Its mechanism of action may involve the protection of pancreatic beta cell function, increased insulin sensitivity, and regulation of glucose metabolism. Animal models show that N-methylgenistein can reduce plasma glucose levels, improve glucose tolerance, and alleviate diabetes related metabolic disorders. In addition, its antioxidant and anti-inflammatory properties also help to alleviate the complications of diabetes.
As a selective ligand for nicotine receptors in the central nervous system, N-methylquercetin exerts analgesic effects by regulating neurotransmitter release and neural signal transduction. Multiple studies on neuropathic pain models have shown that N-methylquercetin can alleviate pain responses caused by mechanical and thermal stimuli, and its analgesic effect is closely related to the activation of nicotine receptor subtypes. This provides a theoretical basis for its application in the treatment of chronic pain and neuropathic pain.
N-Methylquercetin exhibits excellent anti-inflammatory effects, mainly achieved by inhibiting the release of inflammatory mediators and regulating immune cell function. In vitro cell experiments have shown that it can inhibit the expression of pro-inflammatory cytokines such as TNF - α, IL-1 β, and IL-6, and alleviate inflammatory responses. The in vivo inflammatory model also confirms its protective effect on diseases such as arthritis and inflammatory bowel disease.
In recent years, N-methylquercetin has shown potential value in anti malaria research. Its targets include various key proteins of malaria parasites, such as PFCRT, PFMDR1, PFDHFR, PFK13, PFATP6, PFCYTBC, PFPK, PFCYT, PFCYTb, and PfATG8. These targets involve multiple biological processes such as drug tolerance, metabolism, and autophagy in malaria parasites. N-Methylquercetin may interfere with the survival and reproduction of malaria parasites by interacting with these targets, demonstrating potential for anti malaria effects.
The pharmacological effects of N-methyl quercetin mainly rely on its high affinity binding to acetylcholine nicotinic receptors (nAChRs) in the central nervous system. This compound exhibits a high affinity for nicotinic acetylcholine receptors in squid optic ganglia with a Kd of approximately 50 nM, indicating that it is a potent receptor ligand. By activating or regulating nAChRs, N-methylquercetin can affect the release of neurotransmitters, regulate neural excitability, and thus achieve analgesic and neuroprotective effects.
In terms of anti-inflammatory and hypoglycemic mechanisms, N-methyl quercetin may alleviate inflammation and oxidative stress by regulating the expression of NF - κ B signaling pathway and related inflammatory mediators. In addition, its regulatory effect on the insulin signaling pathway also provides a molecular basis for its hypoglycemic effect.
The anti malaria effect involves a multi-target mechanism. N-Methylquercetin can bind to Plasmodium membrane proteins PFCRT and PFMDR1, affecting drug efflux and resistance; Acting on PFDHFR to inhibit folate metabolism and interfere with nucleic acid synthesis; Targeting PFK13 and PFATP6 affects energy metabolism and calcium homeostasis; Regulating the autophagy process involving PfATG8 and disrupting the cellular homeostasis of malaria parasites. These multi-target effects make it a potential candidate for the development of antimalarial drugs.
The pharmacological parameters of N-methyl quercetin indicate that it has good potential for drug development. The molecular weight of 204.2730 conforms to Lipinski's rule, and the LogP value of 0.3319 indicates moderate lipophilicity, which is beneficial for in vivo distribution and cell membrane penetration. The TPSA value of 25.2400 is below 90, supporting its good oral absorption and blood-brain barrier penetration ability. Preclinical data also confirms its high BBB permeability, making it suitable for the treatment of central nervous system diseases.
In terms of toxicological evaluation, N-methyl quercetin did not show hERG channel inhibition, reducing the risk of cardiac toxicity. The Ames test result is 0.0, indicating no significant genetic toxicity. In addition, moderate water solubility (46.4068) is beneficial for formulation development and in vivo absorption.
Pharmacokinetic studies are still in the preliminary stage, and existing data indicate that N-methylquercetin is well absorbed orally and widely distributed in the body, especially at high concentrations in brain tissue. The metabolic pathway mainly involves the liver enzyme system, and the safety of metabolites is good. Excretion is mainly completed through the kidneys, with a moderate half-life, supporting the dosage design of clinical medication.
Based on its multiple pharmacological activities and good drug properties, N-methyl quercetin has shown broad prospects in clinical applications. Firstly, its high affinity for nicotinic receptors in the central nervous system makes it a novel candidate drug for the treatment of neurological disorders such as chronic pain and neurodegenerative diseases. Secondly, its hypoglycemic and anti-inflammatory effects provide a possibility for its application in diabetes and related complications. Again, the multi-target action against malaria gives it a unique advantage in the development of anti malaria drugs, especially in the context of increasingly severe drug resistance, making the development of new anti malaria drugs urgent.
Future research should focus on in-depth analysis of its molecular mechanism of action, optimizing extraction and purification processes, conducting systematic pharmacokinetic and toxicological evaluations, and designing reasonable clinical trial protocols. In addition, based on structural optimization and drug design, the development of derivatives or combination therapy strategies of N-methyl quercetin is expected to enhance its efficacy and safety, and expand its clinical application scope.
N-Methylquercetin, as a natural tricyclic quinoline alkaloid with unique structure and diverse pharmacological activities, exhibits significant hypoglycemic, analgesic, anti-inflammatory, and anti malaria potential due to its high affinity for nicotinic receptors in the central nervous system. Its good pharmacological parameters and safety evaluation have laid a solid foundation for clinical development. In the future, through interdisciplinary research and in-depth exploration of its mechanism of action and optimization of drug properties, N-methylquercetin is expected to become an important breakthrough in the field of natural product pharmacology, providing new ideas and strategies for the treatment of related diseases.
