Product name: Norboldine
Synonym name: Laurolistine;Laurolitsine;Norisoboidine；(+)-Norboldine

Catalogue No.: BP2011
Cas No.: 5890-18-6(Free base)
Formula: C₁₈H₁₉NO₄
Mol Weight: 349.11
Botanical Source:
Physical Description:
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
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.

HPLC of Norboldine

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

Introduction/Overview

Norboldine (CAS No.: 5890-18-6) is an apophine alkaloid with unique structural characteristics, originally isolated from plants such as Lindera aggregata and Chinese yam (Dioscorea spp.). As a derivative of normorphine, desmethylbordine has molecular structures with substitution characteristics for 2-position and 9-position hydroxyl groups as well as 1- and 10-position methoxy positions, giving it unique biological activity. In recent years, with the deepening development of natural product pharmacology, norambordine has attracted attention due to its inhibitory effect on HIV-1 integrase, demonstrating its potential value in antiviral drug development. Moreover, as a representative of apophine alkaloids, it shows broad application prospects in pharmacological activity studies such as anti-inflammation, anti-tumor, and neuroprotection.

This paper aims to systematically review the chemical structure and physicochemical properties of desmethylpordine, its plant origin, and extraction methods, thoroughly explore its pharmacological activity and mechanism of action, combine druggability evaluation and pharmacokinetic characteristics, and anticipate its potential and future development direction in clinical applications, providing a theoretical basis and research reference for the drug development of this natural product.

Chemical structure and physicochemical properties

Normeboldine belongs to the aporphine alkaloid class, with a molecular formula C19H23NO4 and a molecular weight of 313.35. Its structural features include 2 and 9 hydroxyl (-OH) substitutions in the desmethylmorphine backbone, as well as 1- and 10-position methoxy (-OCH3) substitutions, forming functional groups of phenolic and aromatic ethers. This structure imparts high polarity, with a TPSA (topological pole surface area) of 71.04 Ų, indicating it possesses certain hydrogen bond receptor capacity (five hydrogen bond acceptors), which facilitates stable interactions with biological targets.

The LogP value of desmapoldine is 1.7, showing moderate lipid solubility and facilitating cell membrane penetration, but its blood-brain barrier permeability is low (Low), suggesting that its efficacy in the central nervous system may be limited. Its physicochemical properties are stable and suitable for drug formulation development, but safety indicators such as hepatotoxicity, cardiotoxicity, hERG channel inhibition, and mutagenicity (Ames assay) remain unclear and require further systematic evaluation.

Plant Origins and Extraction Methods

Normapoldine is mainly distributed in plants of the genus Lindera (litsea liquor) and some plants of the genus Dioscorea (Dioscorea spp.). As a traditional Chinese medicinal herb, Litsea Ginger is widely used to treat digestive system diseases and inflammation. Its rhizomes and leaves are rich in apophine alkaloids. Yam is known for its dual-purpose properties as food and medicine, and some types have also been detected with desmethyl beridine.

Common methods for extracting desmethylbordine include:

1. Solvent extraction: Methanol, ethanol, or methanol-water mixed solvents are used for reflux extraction of dry plant powders, effectively dissolving target alkaloids by utilizing their polar characteristics.

2. Liquid-liquid distribution: By adjusting the pH value, alkaloids are transferred from the aqueous phase to the organic phase (such as chloroform or ethyl acetate), achieving preliminary purification.

3. Column chromatography separation: Separation and purification are performed using silica gel or C18 reversed phase columns, combined with gradient elution technology to obtain high-purity desmethylbordine.

4. High-Performance Liquid Chromatography (HPLC) Analysis: Used for qualitative and quantitative detection to ensure the quality and purity of extracts.

In recent years, ultrasound-assisted extraction and microwave-assisted extraction technologies have also been introduced, improving extraction efficiency and purity, reducing solvent usage and extraction time, and providing technical support for industrial production.

Pharmacological activity research

Anti-HIV activity

The most notable pharmacological activity of desmethylpoldine is its inhibition of HIV-1 integrase (IN). HIV-1 integrase is a key enzyme in the viral replication cycle, responsible for integrating viral DNA into the host genome, and is an important target for antiretroviral therapy. In vitro experiments have shown that desmaboldine can effectively inhibit HIV-1 integrase activity, blocking the integration of the viral genome and thereby suppressing viral replication.

In addition, the effects of desmapoldine on other key HIV enzymes such as reverse transcriptase (RT) and protease (PR) still require further research, but its multi-target potential as a natural product offers new ideas for anti-HIV drug development.

Anti-inflammatory activity

Apomorphine alkaloids generally have anti-inflammatory effects. Normapoldine inhibits the nuclear factor κB (NF-κB) signaling pathway and cyclooxygenase-2 (COX-2, PTGS2) expression, reducing the release of inflammatory mediators such as tumor necrosis factor α (TNF-α), demonstrating significant anti-inflammatory effects. This mechanism of action provides a theoretical basis for its application in inflammatory diseases such as arthritis and inflammatory bowel disease.

Antitumor activity

Preliminary studies show that normethordine inhibits proliferation and induces apoptosis in various tumor cell lines. Its mechanism may involve regulating the function of the p53 protein (TP53), inhibiting the expression of the anti-apoptotic protein Bcl-2 (BCL2), and blocking the signaling pathways of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (KDR), thereby suppressing tumor cell growth and angiogenesis.

Neuroprotective effects

Although norambordine has relatively low blood-brain barrier permeability, its inhibitory effect on paraacetylcholinesterase (ACHE) and regulation of pathological processes related to β-amyloid precursor protein (APP) and α-synuclein (SNCA) suggest its potential application value in neurodegenerative diseases such as Alzheimer's and Parkinson's disease.

Mechanism of action and molecular targets

The pharmacological effects of desmethylpoldine depend on its interactions with various molecular targets, with the specific mechanism as follows:

1. HIV-1 integrase inhibition: Normeboldine binds to the active site of integrase, blocking the integration of viral DNA with host chromatin and inhibiting viral replication. Molecular docking and kinetic simulations show that its hydroxyl and methoxy groups participate in key hydrogen bonds and hydrophobic interactions, enhancing binding affinity.

2. Regulation of anti-inflammatory signaling pathways: By inhibiting nuclear translocation of NF-κB, it reduces the expression of pro-inflammatory cytokines (such as TNF-α and IL-6); At the same time, it inhibits COX-2 enzyme activity, reduces prostaglandin synthesis, and alleviates inflammatory responses.

3. Tumor-related signaling pathway intervention: regulates p53-mediated cell cycle and apoptosis pathways, reduces Bcl-2 expression, and promotes tumor cell apoptosis; It simultaneously inhibits EGFR and KDR signaling, blocking tumor proliferation and angiogenesis.

4. Neuroprotective mechanism: Inhibits acetylcholinesterase activity, prolongs the duration of acetylcholine's action, and improves cognitive function; Regulates APP and SNCA protein metabolism, slowing neurotoxic protein aggregation.

Druggability evaluation and pharmacokinetics

The druggability parameters of desamporidine indicate that it has certain potential for drug development:

• The molecular weight (313.35) is moderate, complying with the Lipinski rule, which is beneficial for oral absorption.
• LogP(1.7) indicates good lipid-water compatibility, facilitating cell membrane penetration.
• TPSA (71.04 Ų) is moderate, supporting good bioavailability.
• The number of hydrogen bond receptors (5) is suitable for stable binding to protein targets.

However, the low blood-brain barrier permeability of desmapoldine limits its direct application in central nervous system diseases. In terms of safety, key indicators such as hepatotoxicity, cardiotoxicity, and hERG channel inhibition remain unclear and require systematic in vivo and vitro toxicology studies for evaluation.

Pharmacokinetic data are currently lacking. Future research should focus on its absorption, distribution, metabolism, and excretion (ADME) characteristics, especially the evaluation of metabolic pathways and the activity and safety of metabolites.

Prospects and outlooks for clinical applications

Normethoridine, as a natural apomorphine alkaloid with multi-target effects, demonstrates broad pharmacological activity, especially showing significant potential in the anti-HIV field. Its inhibitory effect on HIV-1 integrase provides an important chemical backbone and lead compound for the development of novel antiretroviral drugs. In addition, the anti-inflammatory, antitumor, and neuroprotective effects of desmoboldine have expanded its clinical application possibilities.

Future research should focus on:

1. Structural optimization and derivatives design: Chemical modification enhances targeting activity and pharmacokinetic performance, addressing poor blood-brain barrier permeability and potential toxicity.

2. Systematic pharmacological and toxicological evaluation: clarifying its safety, especially liver and cardiac toxicity, to ensure safety for clinical use.

3. In vivo efficacy and mechanism validation: Animal models were used to verify its antiviral, anti-inflammatory, and antitumor effects, further elucidating molecular mechanisms.

4. Multi-target combination therapy strategy: combining other antiviral or antitumor drugs to create synergistic effects and improve treatment outcomes.

5. Preclinical and clinical research: Promoting norapoldine and its derivatives into clinical trials to evaluate their efficacy and safety.

Conclusion

As a naturally derived apomorphine alkaloid, desamboldine demonstrates significant drug development value due to its unique chemical structure and diverse pharmacological activities, especially its inhibitory effect on HIV-1 integrase. Although its druggability and safety data are still incomplete, with the development of modern medicinal chemistry and pharmacological technologies, noramopoldine is expected to become a novel candidate for antiviral and various disease treatments. In the future, through systematic structural optimization, mechanistic research, and clinical evaluation, Norbupoldine is expected to secure a place in the field of natural product drug development, driving innovation and progress in related disease treatment strategies.