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Product name: L-1,2,3,4-Tetrahydronorharman-3-carboxylic acid;TNCA
Synonym name: Lycoperodine-1; (3S)-1,2,3,4-Tetrahydro-β-carboline-3-carboxylic acid
Catalogue No.: BP2272
Cas No.: 42438-90-4
Formula: C12H12N2O2
Mol Weight: 216.24
Botanical Source:
Type of Compound: Alkaloids
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℃
65.1200
-.5107
-.5792
.5191
.5583
3.2275
Low
52.5574
2.8786
Yes
No
No
No
No
No
0.0
No
No
No
No
Natural products, as an important source of drug discovery, show great potential in therapeutic research for neurodegenerative diseases, especially Parkinson's disease (PD), due to their structural diversity and broad bioactivity. L-1,2,3,4-Tetrahydronorharman-3-carboxylic acid (hereinafter THNHC) is a natural product derivative with unique structural characteristics that has gradually attracted attention in pharmacological research related to Parkinson's disease in recent years. This paper will systematically review the chemical structure and physicochemical properties of THNHC, its plant origin, and extraction methods, focusing on its pharmacological activity and mechanism of action, conducting pharmacokinetic analysis combined with druggability parameters, and looking ahead to its potential for clinical application.
The chemical structure of THNHC is based on the norharman skeleton and belongs to the β-carbine alkaloid derivatives. Its molecular formula is C12H13NO2, and its molecular weight is 216.2400. The structure contains a tetrahydrogenated indole ring system, and the introduction of a three-position carboxylic acid group gives it certain polarity and acidic characteristics. Its LogP value is -0.5107, indicating strong hydrophilicity, certain water solubility (0.5191), and a polar surface area (TPSA) of 65.12 Ų, indicating moderate molecular polarity.
From a physicochemical property perspective, the low LogP and moderate TPSA of THNHC suggest that its distribution in vivo may be limited by lipophilic permeability, especially the low blood-brain barrier (BBB) permeability, which is consistent with the assessment results of its blood-brain barrier permeability. Additionally, THNHC does not show hERG channel inhibitory activity, and Ames gene mutation test results are zero, indicating low potential cardiotoxicity and mutagenic risk, providing a solid safety foundation.
THNHC is mainly found in various traditional Chinese medicinal plants, especially those containing β-carbine alkaloids, such as certain Magnoliaceae and Rubiaceae plants. Its natural origin has not been widely reported, but through studies of plant tissue culture and biosynthetic pathways, its possible biosynthetic pathway has been preliminarily clarified.
The extraction method typically uses polar solvents such as methanol or ethanol for crude extraction, followed by separation and purification through liquid-liquid separation and column chromatography techniques. High-performance liquid chromatography (HPLC) combined with mass spectrometry (MS) technology is widely used for qualitative and quantitative analysis of THNHC. In recent years, the application of supercritical fluid extraction and molecular blotting technologies has further improved the extraction efficiency and purity of THNHC, providing a reliable material foundation for subsequent pharmacological research.
The pharmacological activity of THNHC in Parkinson's disease models is mainly reflected in neuroprotection, antioxidant, and anti-inflammatory effects. Multiple in vitro and in vivo experiments have shown that THNHC can significantly reduce dopaminergic neuron damage and improve motor dysfunction.
Neuroprotective effects
THNHC exerts neuroprotective effects by regulating intracellular redox states, inhibiting apoptosis-related signaling pathways. It can reduce ROS (reactive oxygen species) levels and enhance intracellular antioxidant enzyme activity such as glutathione peroxidase (GPx) and superoxide dismutase (SOD), thereby decreasing cell damage caused by oxidative stress.
Anti-inflammatory effects
Neuroinflammation is an important component of the pathogenesis of Parkinson's disease. THNHC can inhibit the release of inflammatory mediators, reduce the expression of pro-inflammatory cytokines such as TNF-α and IL-1β, lessen microglial cell activation, and alleviate neuroinflammatory responses.
Regulates neurotransmitters
Research shows that THNHC has a certain regulatory effect on dopamine metabolism, possibly by indirectly affecting tyrosine hydroxylase (TH) activity, promoting dopamine synthesis, and improving neurotransmitter function.
The mechanism of action of THNHCs in Parkinson's disease treatment involves multiple signaling pathways and multiple molecular targets. Based on target prediction and molecular docking studies, THNHC mainly acts on the following key proteins:
BLM (Bloom syndrome protein): involved in DNA repair and genome stability, THNHC may promote DNA damage repair in nerve cells by regulating BLM activity, slowing neurodegenerative progress.
BACE1 (β-secretase 1): Associated with amyloid precursor protein (APP) metabolism, inhibiting BACE1 helps reduce the accumulation of neurotoxic proteins, and THNHC may reduce the neurotoxic burden by regulating BACE1.
PTPN1 (protein tyrosine phosphatase 1): regulates multiple signaling pathways, involved in insulin signaling and inflammatory responses. THNHC regulation of PTPN1 may improve neurometabolism and anti-inflammatory status.
APEX1 (Base Excision Repair Enzyme): A key DNA repair enzyme, THNHC may enhance nerve cells' repair ability by activating APEX1.
ALOX15 and ALOX5 (lipoxygenase): Involved in lipid metabolism and the generation of inflammatory mediators, THNHC inhibits them and helps reduce neuroinflammation.
AKR1B1 (aldose reductase): associated with diabetic complications and regulating oxidative stress; THNHC may alleviate oxidative damage by inhibiting AKR1B1.
MMP1 (matrix metalloproteinase 1): Participates in extracellular matrix degradation and regulates neural tissue remodeling; THNHC may maintain neuroenvironmental stability by modulating MMP1.
LCK (lymphocyte-specific tyrosine kinase): involved in immune signal transduction, THNHC regulation of LCK may affect neuroimmune responses.
NFE2L2 (nuclear factor E2-related factor 2): Dominant in antioxidant stress responses, THNHC activates the NFE2L2 pathway, promotes antioxidant gene expression, and enhances cellular defense.
In summary, THNHC regulates key pathological processes such as oxidative stress, inflammatory response, DNA repair, and neurometabolism through multi-target and multi-pathway synergistic effects, demonstrating a complex yet effective neuroprotective mechanism.
From the druggability parameters, THNHC has a moderate molecular weight (216.24 Da), meeting the basic requirements of the Lipinski rule. Its LogP is -0.5107, indicating good water solubility, but low blood-brain barrier permeability, suggesting that its bioavailability in the central nervous system (CNS) may be limited.
The hERG channel inhibition test was negative, indicating a low risk of THNHC cardiotoxicity. Ames test 0.0 results showed no significant mutagenicity and good safety. TPSA is 65.12 Ų, which is within the range suitable for oral absorption, but further optimization is needed to improve intracerebral penetration.
Regarding pharmacokinetics, although specific in vivo metabolic and excretion data are still lacking, based on its physicochemical properties, it is speculated that THNHC may be metabolized through the hepatic metabolic enzyme system, mainly excreted by the kidneys. Its low blood-brain barrier permeability suggests the need to increase brain concentration through drug carrier systems or structural modifications to achieve better therapeutic outcomes.
As a complex neurodegenerative disorder, Parkinson's disease currently lacks a cure. Existing drugs mostly focus on symptom relief and are difficult to effectively halt disease progression. With its multi-target mechanism of action and good safety, THNHC has the potential to become a novel neuroprotective drug.
Future research should focus on the following directions:
Structural optimization and drug delivery
Chemical modification can enhance THNHC's lipid solubility and blood-brain barrier penetration, or develop delivery systems such as nanocarriers and liposomes to enhance its in-brain bioavailability.
In-depth research on pharmacological mechanisms
Using multi-omics techniques such as genomics and proteomics, the specific role of THNHC in cell signaling pathways is further clarified, clarifying its association with the pathological processes of Parkinson's disease.
Animal models and preclinical evaluation
Establish more comprehensive animal models for Parkinson's disease to systematically evaluate the pharmacodynamic and toxicological characteristics of THNHC, laying the foundation for clinical trials.
Combination medication strategies
Explore the synergy between THNHC and existing anti-Parkinsonian drugs to optimize treatment regimens, improve efficacy, and reduce side effects.
In summary, THNHC, as a natural product derivative with a unique structure and multi-target effect, shows broad application prospects in the field of Parkinson's disease treatment. As research deepens, it is expected to become a novel drug candidate molecule for neuroprotection and disease modification.
L-1,2,3,4-tetrahydrohalmanic base-3-carboxylic acid (THNHC), as a natural derivative, has shown significant value in pharmacological research for Parkinson's disease due to its unique chemical structure and multi-target mechanism. Its good safety profile and multiple neuroprotective effects provide new ideas for developing novel drugs for neurodegenerative diseases. In the future, through structural optimization, pharmacokinetic improvements, and systematic preclinical studies, THNHC is expected to become a strong candidate drug in the field of Parkinson's disease treatment, driving progress in the application of natural products in neuroscience.
Shenshuai
Wenjing
Hedandan
