Synonym name:
Catalogue No.: BP0464
Cas No.: 67909-49-3
Formula: C₁₉H₁₅N₃O
Mol Weight: 301.35
Botanical Source: Alkaloid from the unripe fruit of Evodia rutaecarpa (Rutaceae)

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, up tp kilograms.

For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.

HNMR of Dehydroevodiamine

HPLC of Dehydroevodiamine

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Dehydroevodiamine (DHEVD), CAS number 67909-49-3, is a quinazolian alkaloid isolated from the traditional Chinese medicinal herb Evodiae fructus. As one of the important active components in evodia, dehydroevodia alkaloid has attracted widespread attention in recent years due to its multi-target pharmacological activity. Research shows that DHEVD not only has a significant protective effect on the cardiovascular system, especially in antiarrhythmia, but also demonstrates its ability to regulate inflammatory responses, particularly in suppressing inflammatory mediator expression in macrophages. Moreover, its multi-target effect in the field of analgesia has laid the foundation for its development as a novel analgesic drug.

This paper will systematically review the chemical structure and physicochemical properties of dehydroevoderine alkaloids, plant origins and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, and finally look ahead to its clinical application prospects, aiming to provide researchers in the field of natural product pharmacology with comprehensive and in-depth reference materials.

Chemical structure and physicochemical properties

Dehydroevodiacriline belongs to the quinazoliline alkaloids, with a molecular formula of C19H19N3O and a molecular weight of 301.3490. Its molecular structure centers on the quinazolin backbone, containing multiple aromatic rings and nitrogen heterocycles, giving it unique chemical properties and biological activity. The LogP value is 0.2822, indicating moderate lipid solubility, which facilitates penetration through cell membranes. The polar surface area (TPSA) is 39.98 Ų, and its lower polarity helps it cross the blood-brain barrier, matching its activity in the central nervous system.

Water solubility is 0.3054, indicating limited solubility in water but sufficient to support absorption in the body. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames test result was 1.8, indicating a low genotoxicity risk and meeting drug safety requirements.

In summary, the physicochemical properties of dehydroevoderine are suitable for its development as a drug molecule, especially in the fields of central nervous system and cardiovascular diseases.

Plant Origins and Extraction Methods

Dehydroevodiae is mainly found in Evodiae fructus, a dried mature fruit of a plant in the Rutaceae family, and is widely used in traditional Chinese medicine to treat stomach pain, headache, and cold-damp pain. Evodia is mainly distributed in southern China and Southeast Asia, with a long medicinal history and rich chemical components.

Common methods for extracting dehydroevoderine include:

1. Solvent extraction method: Using ethanol or methanol as solvent, extracting alkaloids from evodia via reflux or ultrasound assistance.

2. Acid-base precipitation method: Utilizes the alkaline characteristics of alkaloids to precipitate by adjusting the pH value, further purifying.

3. Column chromatography separation: Using silica gel or C18 inverted column chromatography technology combined with gradient elution achieves efficient separation and purification of dehydroevodiacaline alkaloids.

4. High-Performance Liquid Chromatography (HPLC): Used for qualitative and quantitative analysis and purity testing to ensure extract quality.

In recent years, supercritical CO2 extraction and molecular blotting technologies have also been attempted to improve the extraction efficiency and purity of dehydroevoderine (Evodiacaline), promoting its feasibility for large-scale production.

Pharmacological activity research

Antiarrhythmic effects

Dehydroevodine exhibited significant antiarrhythmic effects on ventricular myocytes in guinea pigs. Experimental data show that DHEVD can regulate the action potentials of myocardial cells, prolong the effective refractory period, and inhibit abnormal excitation conduction, thereby reducing the occurrence of arrhythmias. Its mechanism of action may involve regulation of potassium ion channels, improving the electrophysiological properties of the myocardium, and has potential clinical value.

Anti-inflammatory effects

Dehydroevodine demonstrates good anti-inflammatory activity in inflammation models. In particular, in LPS (lipopolysaccharide)-induced mouse macrophages, DHEVD significantly inhibits the expression of induced nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and nuclear factor κB (NF-κB), thereby reducing inflammatory responses. This action suggests that it may exert anti-inflammatory effects by inhibiting the NF-κB signaling pathway, reducing the release of pro-inflammatory factors.

Analgesic effect

Research on dehydroevoderine in analgesia shows that it acts on various pain-related targets, including TRPV1 (vanilla acid subtype 1 with transient receptor potential), CNR1 (cannabinoid receptor 1), OPRD1 (δ-opioid receptor), PTGS1 (cyclooxygenase-1), TRPA1 (vanillin subtype A1), PTGS2 (cyclooxygenase-2), SLC6A4 (serotonin transporter), OPRM1 (μ-opioid receptor), OPRK1 (κ-opioid receptor) and DRD2 (dopamine D2 receptor), among others. Through multi-target synergistic effects, DHEVD can effectively alleviate inflammatory and neuropathic pain, demonstrating potential as a novel analgesic drug.

Other pharmacological activities

Some studies have also found that dehydroevodiacriline has neuroprotective effects, possibly reducing nerve cell damage by regulating neurotransmitters and antioxidant mechanisms. In addition, it also has certain effects on blood pressure regulation and gastrointestinal motility, but related research is still in its early stages.

Mechanism of action and molecular targets

The multi-target mechanism of dehydroevoderine is the basis for its pharmacological diversity. The main mechanisms include:

1. Regulating ion channels: By modulating potassium and calcium channels within myocardial cells, it extends the refractory period of action potentials, suppresses abnormal electrical activity, and prevents arrhythmias.

2. Inhibition of NF-κB signaling pathway: NF-κB is a key transcription factor in inflammatory responses. DHEVD reduces the expression of iNOS, COX-2, and PGE2 by inhibiting its activation, thereby alleviating inflammation.

3. Multi-target analgesic mechanism:D HEVD acts on pain receptors such as TRPV1 and TRPA1, inhibiting pain signal transmission; simultaneously activates opioid receptors (OPRD1, OPRM1, OPRK1) and cannabinoid receptor CNR1, enhancing endogenous analgesic effects; Regulates the serotonin transporter SLC6A4 and the dopamine D2 receptor DRD2, participating in central nervous system pain regulation.

4. Antioxidant and neuroprotection: By scavenging free radicals and regulating intracellular antioxidant enzyme activity, nerve cells are protected from oxidative stress damage.

The synergistic effects of these mechanisms enable dehydroevoderine to demonstrate broad therapeutic potential in cardiovascular, inflammatory, and neurological diseases.

Druggability evaluation and pharmacokinetics

From the perspective of druggability parameters, dehydroevoderine has promising potential for drug development. Its molecular weight is moderate (301.3490), meeting the requirements of the Lipinski rule. The LogP value was 0.2822, indicating suitable lipid-water phase balance, which is beneficial for distribution in vivo and cell membrane penetration. The TPSA was 39.98, and its low polarity helps it cross the blood-brain barrier, which aligns with its central nervous system pharmacological activity.

Although water solubility is limited (0.3054), formulation optimization can improve oral bioavailability. hERG channel inhibition was negative, reducing the risk of cardiotoxicity. Ames test results indicate that it carries a low genotoxicity risk and is relatively safe.

Pharmacokinetics, dehydroevoderine has a high blood-brain barrier crossing ability, indicating that its effective concentration in the central nervous system is easily achieved. The metabolic pathway in vivo is not yet fully understood, but preliminary studies suggest it is mainly processed by hepatic metabolic enzyme systems, and the activity and toxicity of these metabolites require further study.

Overall, dehydroevoderine performs well in terms of pharmacokinetics and safety, providing a foundation for further clinical development.

Prospects and outlooks for clinical applications

Due to its multi-target and multi-mechanism pharmacological properties, dehydroevodiacriline has broad clinical application prospects in cardiovascular diseases, inflammatory diseases, and pain management.

1. Arrhythmia treatment: Most existing antiarrhythmic drugs have side effects and resistance issues. DHEVD, as a natural product, offers good safety and multiple regulatory effects, and is expected to become a new generation of antiarrhythmic drugs.

2. Anti-inflammatory and immunomodulatory: By inhibiting the expression of NF-κB and inflammatory mediators, DHEVD can be used to treat chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease, offering new therapeutic approaches.

3. Analgesic drug development: For neurological and inflammatory pain, DHEVD's multi-target mechanism helps overcome the dependence and resistance of traditional analgesics and develops safe and effective new analgesics.

4. Neuroprotection and cognitive impairment: Preliminary studies show its potential in neuroprotection, and future applications may be explored in neurodegenerative diseases such as Alzheimer's and Parkinson's.

However, clinical research on dehydroevoderine is still relatively limited, urgently requiring systematic pharmacodynamics, safety evaluation, and clinical trial support. In addition, optimization of formulation processes, in-depth research on pharmacokinetics, and molecular-level analysis of mechanisms of action are also key areas of future research.

Conclusion

Dehydroevodia alkaloid, an important alkaloid component in Evodia, shows broad application prospects in antiarrhythmia, anti-inflammation, and pain relief due to its unique chemical structure and multi-target pharmacological activity. Its favorable druggability parameters and low toxicity risk provide favorable conditions for clinical translation. In the future, through in-depth mechanistic research, pharmacokinetic optimization, and clinical validation, dehydroevoderine is expected to become an important representative of the new generation of natural medicines, bringing new hope for the treatment of related diseases.

With continuous advances in natural product pharmacology and modern drug development technologies, research and application of dehydroevoderine will see broader development prospects, advancing the application of natural medicines in modern medicine to new heights.