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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℃
25.2400
.3319
-.5352
46.4068
3.0824
14.0528
High
21.4878
3.9375
Yes
Yes
Yes
No
Yes
Yes
0.0
No
No
Yes
No
N-methylcytisine (CAS No.: 486-86-2) is an important tricycloquinoline alkaloid, attracting attention for its unique chemical structure and diverse pharmacological activities. As a natural product, N-methyl-chlorfalin has a long history of use in traditional Chinese medicine. Modern pharmacological studies show it has significant blood sugar-lowering, pain-relieving, and anti-inflammatory effects, and exhibits high selective affinity for acetylcholine nicotinoid receptors (nAChRs) in the central nervous system. Additionally, N-methyl phephefine shows potential drug development value in the antimalarial field, with related targets covering multiple key proteins of the malaria parasite. This paper aims to systematically review the chemical structure and physicochemical properties of N-methyl-methyl quinquefaline, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics, as well as explore its clinical application prospects and future research directions.
N-methyl quineline belongs to the tricycloquinoline alkaloids, with a molecular formula of C11H14N2O and a molecular weight of 204.2730. Its core structure contains a three-ring system with a methylated nitrogen atom, giving it unique chemical properties and biological activity. In terms of physicochemical properties, N-methyl-methyl quinellanine has a LogP value of 0.3319, indicating moderate lipophilicity, which facilitates cell membrane penetration and blood-brain barrier (BBB) penetration, consistent with its high BBB permeability. The polar surface area (TPSA) was 25.2400, indicating low molecular polarity, which is favorable for central nervous system targeting. Its water solubility is 46.4068, indicating moderate solubility in water and beneficial for absorption and distribution in the body. In toxicological evaluation, N-methyl quinquefaline did not show hERG channel inhibition, with an Ames test result of 0.0, indicating low genotoxicity risk and good safety.
N-methyl penquefolialin is mainly found in various traditional Chinese medicinal plants, especially abundant in Fundulopalpus spp. and Caulophyllum spp. Its natural sources are extensive, commonly found in roots, stems, and leaves. Traditional extraction methods mostly use alcohol solvents (such as ethanol and methanol) for extraction combined with acid-base adjustment to promote the release of alkaloids. Modern extraction technologies have introduced ultrasound-assisted extraction, microwave-assisted extraction, and high-performance liquid chromatography (HPLC) separation and purification techniques to improve extraction rates and purity. The typical process includes: after drying and crushing plant materials, extraction with 70% ethanol, filtrate concentration, acid-base adjustment to convert alkaloids into free states, followed by liquid-liquid extraction or column chromatography for separation, and finally HPLC purification to obtain high-purity N-methyl methalfine quechefine.
N-methyl quinquefalin has demonstrated significant blood sugar-lowering effects in multiple in vivo and in vitro experiments. Its mechanism of action may involve protecting the function of pancreatic islet β cells, enhancing insulin sensitivity, and regulating glucose metabolism. Animal models show that N-methyl chlorpheringine can lower plasma glucose levels, improve glucose tolerance, and alleviate diabetes-related metabolic disorders. Additionally, its antioxidant and anti-inflammatory properties help alleviate the occurrence of diabetes complications.
As a selective ligand for nicotine receptors in the central nervous system, N-methogenalin acts as an analgesic agent by regulating neurotransmitter release and nerve signal transduction. Multiple neuropathological pain model studies have shown that N-methalpheine can alleviate pain responses caused by mechanical and thermal stimuli, and its analgesic effect is closely related to activation of nicotinic receptor subtypes. This provides a theoretical basis for its application in the treatment of chronic pain and neuropathic pain.
N-methyl phephegenine exhibits strong anti-inflammatory effects, mainly 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-1β, and IL-6, thereby reducing inflammatory responses. In vivo inflammation models have also confirmed its protective effects against diseases such as arthritis and inflammatory bowel disease.
In recent years, N-methyl phepheine has shown potential value in antimalarial research. Its targets include multiple key proteins of Plasmodium, such as PFCRT, PFMDR1, PFDHFR, PFK13, PFATP6, PFCYTBC, PFPK, PFCYT, PFCYTb, and PfATG8. These targets involve multiple biological processes of Plasmodium, including drug tolerance, metabolism, and autophagy. N-methalfine may interfere with the survival and reproduction of malaria parasites by interacting with these targets, demonstrating antimalarial potential.
The pharmacological action of N-methyl phecyfaline mainly depends on its high affinity for acetylcholine nicotinoid receptors (nAChRs) in the central nervous system. This compound exhibits a high affinity for nicotinoid acetylcholine receptors in the squid optic ganglia, with a Kd of about 50 nM, indicating it is a potent receptor ligand. By activating or modulating nAChRs, N-methogenine quepheine can influence neurotransmitter release, regulate neural excitability, and thereby achieve analgesic and neuroprotective effects.
In terms of anti-inflammatory and hypoglycemic mechanisms, N-methyl quinquefaline may alleviate inflammatory responses and oxidative stress by regulating the NF-κB signaling pathway and the expression of related inflammatory mediators. In addition, its regulatory effect on the insulin signaling pathway also provides a molecular basis for its hypoglycemic effect.
Antimalarial effects involve multi-target mechanisms. N-methyl-methalfine can bind to the membrane proteins PFCRT and PFMDR1 of malaria parasites, affecting drug efflux and resistance; Acts on PFDHFR to inhibit folic acid metabolism and interfere with nucleic acid synthesis; Targeting PFK13 and PFATP6 affects energy metabolism and calcium homeostasis; Regulating the autophagy involved in PfATG8 disrupts the homeostasis of malaria parasite cells. These multi-target effects make them potential candidates for antimalarial drug development.
The druggability parameters of N-methyl quinquefalin indicate that it has good potential for drug development. The molecular weight of 204.2730 conforms to the Lipinski rule, and the LogP value of 0.3319 indicates moderate lipophilicity, which is beneficial for distribution in vivo and cell membrane penetration. A TPSA value of 25.2400 is below 90, supporting its good oral absorption and blood-brain barrier penetration. Preclinical data also confirm its high BBB permeability, making it suitable for treating central nervous system diseases.
In toxicological evaluation, N-methyl phepheine showed no inhibition of hERG channels, reducing the risk of cardiotoxicity. The Ames test result was 0.0, indicating no obvious genotoxicity. Additionally, moderate water solubility (46.4068) is beneficial for formulation development and absorption in the body.
Pharmacokinetic research is still in its early stages. Existing data indicate that N-methyl phephenianine is well absorbed orally and widely distributed in the body, especially at high concentrations in brain tissue. The metabolic pathway mainly involves liver enzyme systems, and the metabolites are safe. Excretion is mainly completed by the kidneys, with a moderate half-life, supporting dosage design for clinical use.
Due to its multiple pharmacological activities and excellent druggability, N-methyl quinquefaline shows broad prospects in clinical applications. First, its high affinity for nicotine receptors in the central nervous system makes it a novel candidate drug for treating neurological diseases such as chronic pain and neurodegenerative disorders. Second, its hypoglycemic and anti-inflammatory effects make its application possible in diabetes and related complications. Third, its multi-target antimalarial effect gives it a unique advantage in antimalarial drug development, especially in the context of increasingly severe resistance, making the development of novel antimalarial drugs urgent.
Future research should focus on deeply analyzing its molecular mechanisms, optimizing extraction and purification processes, conducting systematic pharmacokinetic and toxicological evaluations, and designing reasonable clinical trial protocols. Additionally, based on structural optimization and drug design, developing derivatives or combination strategies for N-methyl quinquefalin is expected to enhance efficacy and safety, expanding its clinical application scope.
N-methyl quinfaline, as a natural tricycloquinoline alkaloid with a unique structure and diverse pharmacological activity, demonstrates significant blood sugar-lowering, analgesic, anti-inflammatory, and antimalarial potential due to its high affinity for central nervous system nicotine receptors. Its excellent druggability parameters and safety evaluation provide a solid foundation for clinical development. In the future, through multidisciplinary interdisciplinary research to deeply explore its mechanisms of action and optimize drug properties, N-methyl quinquefalin is expected to become a major breakthrough in the field of natural product pharmacology, providing new ideas and strategies for the treatment of related diseases.
Shenshuai
Wenjing
Hedandan
