Synonym name: Cephaelin Dihydrochloride
Catalogue No.: BP0329
Cas No.: 5853-29-2
Formula: C₂₈H₃₈N₂O₄.2HCl
Mol Weight: 539.538
Botanical Source:

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.

HPLC of Cephaelin Hydrochloride

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

Introduction/Overview

Cephaelin hydrochloride (CAS No.: 5853-29-2), a natural alkali compound, has attracted widespread attention due to its remarkable anti-amebiasis activity. Amebiasisis, especially intestinal infections caused by the pathogenic amoeba Entamoeba histolytica, is a major global public health challenge, particularly prevalent in developing countries. Traditional treatments such as metronidazole are effective but suffer from resistance and side effects, prompting researchers to actively explore novel anti-amoeba drugs. Due to its unique chemical structure and biological activity, ephemerolalkaloid hydrochloride has become a research hotspot in the field of natural product pharmacology.

This paper will systematically review the chemical structure and physicochemical properties of emethalolic alkaloid hydrochloride, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics. Combined with its molecular targets, it will explore its potential as an anti-amoeba drug and look ahead to future clinical application prospects.

Chemical structure and physicochemical properties

Syngenolic alkaloid hydrochloride belongs to the isoquinoline alkaloids, with the molecular formula C27H33NO9 and a molecular weight of 535.53. Its structure contains multiple phenolic hydroxyl groups and ether bonds, giving it strong polarity and the ability to form multi-point hydrogen bonds. Its LogP value is about 1.89, indicating moderate lipid solubility, which facilitates cell membrane penetration without excessive lipophilus, balancing bioavailability and water solubility. The total polar surface area (TPSA) is 71.69 Ų, with 6 hydrogen bond acceptors, indicating strong binding potential in intermolecular interactions.

Structurally, emethalolic alkaloid hydrochloride is in hydrochloride form, which increases its water solubility and stability, facilitating drug formulation development. The complexity of its molecular structure and multifunctional groups provide the basis for its binding to various biological targets.

Plant Origins and Extraction Methods

Eparic root phenolic alkali hydrochloride mainly comes from the traditional Chinese medicinal material Tugen (Cephaelis ipecacuanha) and its related plant species and genera. Tugen belongs to the Rubiaceae family, traditionally used to treat dysentery and digestive system diseases. Its roots are rich in isoquinoline alkaloids, with emetylene hydrochloride being one of the main active ingredients.

The extraction process typically uses acidic aqueous solutions or organic solvents (such as methanol, ethanol) to extract dried plant roots, followed by alkaline precipitation and hydrochloric acid salting through acid-base adjustment. The purification steps include liquid-liquid extraction, column chromatography (silica gel column, C18 reversed-phase column), and high-performance liquid chromatography (HPLC) separation to ensure the purity and activity of the target compound. In recent years, the application of ultrasound-assisted extraction and microwave-assisted extraction technologies has improved extraction efficiency and yield, while reducing solvent consumption.

Pharmacological activity research

The main pharmacological activity of emegenolic alkaloid hydrochloride is concentrated in anti-amebiasis, showing significant inhibitory effects on Entamoeba histolytica. In vitro experiments have shown that this compound can effectively inhibit the proliferation and motility of Amoeba, reducing its aggressiveness.

Additionally, emegenolic alkaloid hydrochloride regulates the intracellular enzyme system of Amoeba, interfering with their metabolic and signaling pathways. Some studies have shown that this compound inhibits the permeability and endocytosis of amoeba cell membranes, reducing parasite damage to host cells.

In animal models, emethalic phenolic hydrochloride showed good anti-amoeba infection, reducing intestinal inflammation and tissue damage, and promoting lesion repair. Its anti-inflammatory and immunomodulatory effects have also been partially confirmed by research, supporting its comprehensive therapeutic potential.

Mechanism of action and molecular targets

The anti-amebias mechanism of emegenolalline hydrochloride involves multiple molecular targets, mainly targeting key proteins and receptors of Entamoeba histolytica:

• EHI_115350, EHI_182180, EHI_056990, EHI_089710, EHI_123030: These encoded proteins are involved in the metabolic regulation and maintenance of amoeba cell structure. Etygic phenolic hydrochloride binds to it to interfere with amoeba energy metabolism and cytoskeletal stability, inhibiting their growth and migration.
• EhSTIRP (Entamoeba histolytica Stress-Induced Protein): As a stress protein, it regulates amoeba's ability to adapt to environmental changes. Emegenolalkaloid hydrochloride may reduce parasite viability by inhibiting EhSTIRP expression.
• EhADH (Amoeba Acetaldehyde Dehydrogenase): A key metabolic enzyme involved in the energy metabolism of amoebic enzymes. The compound's inhibitory effect on EhADH directly affects the parasite's metabolic activity.
• EhCP5 (caspase 5): One of the pathogenic factors of amoebae, involved in host tissue destruction and immune escape. Emephylline hydrochloride inhibits EhCP5, helping to alleviate tissue damage.
• Gal/GalNAc receptor: Amoebic surface glycoprotein mediates host cell adhesion; the compound reduces parasite invasion by blocking this receptor.
• EhRab7: GTPase regulates endocytosis and intracellular transport, affecting organelle function of parasites. EhRabine hydrochloride interferes with EhRab7 function and disrupts intracellular material transport of amoebae.

Through multi-target synergistic action, emegenolic alkaloid hydrochloride effectively inhibits the growth, invasion, and pathogenicity of amoebae, demonstrating strong antiparasitic activity.

Druggability evaluation and pharmacokinetics

In terms of druggability parameters, hegenphenolic alkaloid hydrochloride has relatively ideal medicinal properties:

• The molecular weight is 535.53, slightly higher than the ideal range for traditional oral drugs, but still within an acceptable range.
• The LogP was 1.89, indicating moderate lipid and water distribution, which is beneficial for absorption and distribution in the body.
• TPSA was 71.69 Ų, below 140 Ų, indicating good cell membrane permeability.
• It has 6 hydrogen bond receptors, which is moderate and helps form stable binding to target proteins.

However, emerothalic alkaloid hydrochloride does not easily cross the blood-brain barrier (BBB), limiting its application for central nervous system-related parasitic infections. Safety indicators such as hepatotoxicity, cardiotoxicity, and hERG channel inhibition remain unclear and require further systematic evaluation. Ames-induced mutagenic test results are unknown, requiring supplementary genetic toxicology research.

Pharmacokinetics, currently available data are quite limited. Preliminary in vivo studies show that emethalol hydrochloride has moderate bioavailability after oral administration, is mainly metabolized by the liver, has a moderate half-life, and is suitable for daily use. Metabolic pathways may involve the hepatic CYP450 enzyme system, and future studies of these metabolites and drug interactions are needed.

Prospects and outlooks for clinical applications

As a natural anti-amoeba drug candidate, emegenolalkaloid hydrochloride possesses a multi-target mechanism of action and good pharmacological activity, demonstrating broad clinical application potential. Its advantages in anti-amoebiasis treatment include:

• Multi-target synergistic effect reduces resistance risk;
• Naturally sourced, with relatively high safety potential;
• Good oral drug properties, facilitating clinical promotion.

Future clinical development should focus on the following directions:

1. Safety evaluation: Systematic studies on hepatorenal toxicity, cardiotoxicity, and genetic toxicity are conducted to ensure clinical drug safety.
2. Dosage Formulation Optimization: Developing new formulations such as sustained-release and controlled-release formulations to improve efficacy persistence and patient compliance.
3. Combination drug research: Combined with existing anti-amoebic drugs, exploring synergistic effects and resistance overcoming strategies.
4. Clinical trial design: Conduct multicenter, randomized controlled clinical trials to verify efficacy and safety.
5. Expanding indications: Given its effects on various amoebae-related targets, explore its therapeutic potential for other parasitic diseases and related inflammatory diseases.

In addition, the design and synthesis of derivatives based on the structure of amegenolalkaloid hydrochloride will provide important ideas for developing a new generation of highly effective, low-toxicity anti-amoeba drugs.

Conclusion

Epargenolalkaloid hydrochloride, a natural compound with multi-target anti-amoeba activity, demonstrates great potential as a novel anti-amoeba drug due to its unique chemical structure and excellent pharmacological properties. Although research on its safety and pharmacokinetics is still insufficient, its multi-target mechanism of action offers new strategies to overcome existing drug resistance. In the future, through systematic pharmacological and toxicological research, dosage form optimization, and clinical validation, emegenolaline hydrochloride is expected to become a major breakthrough in the field of anti-amebiasis treatment, contributing to global public health.