Product name: Emetine Dihydrochloride
Synonym name: Emetine hydrochloride hydrate(xH2O), 7083-71-8; Emetine dihydrochloride pentahydrate,79300-07-5; Emetine, 483-18-1
Catalogue No.: BP0531-1
Cas No.: 316-42-7
Formula: C₂₉H₄₂Cl₂N₂O₄
Mol Weight: 553.565
Botanical Source: Ipecacuanha
Physical Description: Powder
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.

HPLC of Emetine Dihydrochloride

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

Introduction/Overview

Emetine Dihydrochloride (CAS No.: 316-42-7) is a natural alkaloid compound with a long history of use, mainly extracted from plants of the genus Emetine. As a classic anti-amoebic dysentery drug, emetine dihydrochloride plays an important role globally, especially in treating parasitic infections in tropical and subtropical regions. In recent years, with the deepening of molecular biology and pharmacological research, the pharmacological mechanism, molecular targets, and druggability characteristics of emetriline dishydrochloride have been systematically elucidated, providing a theoretical foundation for optimizing its clinical application and developing new indications.

This paper will provide a comprehensive review of the chemical structure and physicochemical properties of emeline dishydrochloride, plant origin and extraction methods, pharmacological activity studies, mechanisms of action and molecular targets, druggability evaluation and pharmacokinetics, as well as its clinical application prospects, aiming to provide detailed reference materials for researchers in the field of natural product pharmacology.

Chemical structure and physicochemical properties

Syngine dihydrochloride is an isoquinoline alkaloid with the molecular formula C29H40N2O4 and a molecular weight of 480.6490. Its structural features include multiple circular structures and multiple hydrogen bond donors and acceptors, giving it high biological activity. The dihydrochloride form of emethrine improves its water solubility and bioavailability, facilitating drug formulation development.

In terms of physicochemical properties, the LogP value of emethrine dihydrochloride is 4.7671, indicating strong lipophilusibility, which facilitates penetration of cell membranes, especially the high permeability of the blood-brain barrier (BBB). Its topological polar surface area (TPSA) is 52.1900, and moderate polarity helps with drug distribution and targeting in the body. With a water solubility of 0.1942, it is a low-soluble compound, which poses certain challenges to its formulation process.

Toxicological evaluation showed that emethrine dishydrochloride has hERG channel inhibitory activity, suggesting a possible cardiotoxicity risk and requiring close monitoring in clinical use. The Ames test result was 0.0, indicating no significant genotoxicity.

Plant Origins and Extraction Methods

Cephaelis ipecacuanha is mainly derived from plants of the genus Cephaelis ipecacuanha, a perennial herbaceous plant of the Rubiaceae family, native to South America, especially Brazil, Colombia, and Peru. The roots of Synapsis contain abundant alkaloids, with the highest content of Synaphrine.

Traditional extraction processes typically use acidic aqueous solution extraction combined with solvent separation and crystallization purification technologies. The specific steps include:

1. Raw material processing: Root spitting is dried and crushed to increase surface area.
2. Acid extraction: Soak in dilute hydrochloric acid or sulfuric acid solution to promote alkaloid leaching.
3. Alkaline precipitation: Adjust pH to alkalinity to precipitate impurities.
4. Solvent extraction: Use organic solvents such as chloroform or ether to extract target alkaloids.
5. Hydrochloric acid chloride: Alkaloids react with hydrochloric acid to produce hememine dihydrochloride crystals.
6. Purification crystallization: Repeated crystallization to improve purity ultimately yields medicinal-grade emetygine dishydrochloride.

In recent years, the introduction of ultrasound-assisted extraction, microwave-assisted extraction, and membrane separation technologies has improved extraction efficiency and purity, reduced the use of organic solvents, and aligned with the concept of green chemistry.

Pharmacological activity research

The best known pharmacological activity of emegen dihydrochloride is its anti-amoebic dysentery effect. Amoebic dysentery is caused by the protozoan Entamoeba histolytica. Ememine exerts its insecticidal effect by inhibiting the parasite's protein synthesis and energy metabolism.

The main pharmacological activities include:

• Anti-amoebic dysentery: Emetine can effectively inhibit the growth and reproduction of Amoebia eschei, reducing intestinal inflammation and tissue damage.
• Anti-inflammatory effect: By inhibiting the release of inflammatory mediators, it reduces the inflammatory response in host tissues.
• Antitumor potential: Some studies show that emetine inhibits certain tumor cells, possibly by inducing apoptosis and suppressing cell cycle progression.
• Antiviral activity: Preliminary in vitro experiments show inhibition of replication of certain viruses, but the mechanism remains unclear.

Mechanism of action and molecular targets

The anti-amoeba mechanism of emegenal dihydrochloride mainly involves inhibiting parasite-specific proteins and enzymes, interfering with their metabolic and physiological functions. Relevant targets include EHI1, EHI2, EHI3, EHI4, and EHI5, which are specific proteins for Esche's amoebae. The specific mechanisms of action are as follows:

1. Inhibition of protein synthesis: Emetine can bind to amoebic ribosomes, blocking peptide chain extension and causing protein synthesis to stall.
2. Disrupts energy metabolism: By inhibiting mitochondrial function, reducing ATP production, and inducing parasite energy depletion.
3. Damage the cytoskeleton: affects the dynamic balance of microtubules and microfilaments, disrupting cell morphology and motility.
4. Induction of apoptosis: Activates apoptotic signaling pathways within amoeba cells, promoting programmed cell death.

In addition, emetine also affects host cells to some extent, especially by inhibiting hERG potassium channels in myocardial cells, which may lead to the risk of arrhythmias, so clinical monitoring is necessary.

Druggability evaluation and pharmacokinetics

The druggability parameters of Emitaline Dihydrochloride indicate good lipid solubility (LogP 4.7671) and moderate polarity (TPSA 52.1900), which facilitate cell membrane penetration and blood-brain barrier penetration, supporting its potential application in central nervous system-related diseases.

Pharmacokinetic characteristics include:

• Absorption: Oral absorption is good, but bioavailability is greatly affected by first-pass effects.
• Distribution: Widely distributed in tissues within the body, especially crossing the blood-brain barrier to reach the central nervous system.
• Metabolism: Mainly metabolized by the hepatic cytochrome P450 enzyme system, producing various metabolic products.
• Excretion: Excreted in urine and bile, with a moderate half-life.

In terms of toxicity, hERG channel inhibition suggests potential cardiotoxicity, requiring cautious dose adjustment and ECG monitoring. A negative Ames test indicates a low genotoxicity risk.

Prospects and outlooks for clinical applications

As a traditional anti-amoeba drug, emetine dihydrochloride is still widely used in some regions, especially in resource-limited regions. The future clinical application prospects are mainly reflected in the following aspects:

1. Optimization of anti-amoebic dysentery treatment: Reducing side effects and enhancing efficacy through formulation improvements and dosing regimen optimizations.
2. New indication development: Based on its anti-tumor and antiviral potential, conduct preclinical and clinical studies to explore applications in cancer and viral infections.
3. Combination Strategies: Use in combination with other antiparasitic drugs or immunomodulators to enhance treatment outcomes and reduce the risk of resistance.
4. Drug delivery system innovation: Utilizing nanotechnology and targeted delivery systems to improve drug stability and targeting, reducing toxic side effects.

Although emetine dihydrochloride carries certain cardiotoxicity risks, through structural modification and dosage form optimization, safer and more effective derivatives may be developed, expanding its clinical application areas.

Conclusion

As a classic natural product drug, Syngenine dihydrochloride holds an important position in the field of natural product pharmacology due to its unique chemical structure and significant anti-amoeba activity. With the development of modern pharmacology and molecular biology techniques, its mechanisms of action and molecular targets have been deeply analyzed, providing a solid foundation for clinical application and new drug development.

In the future, combining modern drug design concepts with advanced formulation technologies, emethrine dihydrochloride and its derivatives are expected to play a greater role in antiparasitic, anti-tumor, and other disease treatments. Ongoing basic and clinical research will drive improvements in safety and efficacy, fostering innovation in natural product medicines.