Synonym name:
Catalogue No.: BP0195
Cas No.: 71963-77-4
Formula: C₁₆H₂₆O₅
Mol Weight: 298.379
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 Artemether

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

Introduction/Overview

Artemether (CAS number: 71963-77-4), a semi-synthetic derivative of artemisinin, has attracted attention since the late 20th century for its outstanding antimalarial activity. The discovery and application of artemisinin drugs have greatly advanced the treatment of falciparum malaria, especially playing a key role in controlling multidrug-resistant Plasmodium strains. Artemether improves its pharmacokinetics and bioavailability by converting the lactone structure of artemisinin into alcohol methyl ether, making it one of the widely used antimalarial drugs in clinical practice.

In recent years, pharmacological research on artemether has not been limited to the antimalarial field; its potential activities in neurotoxicity, schistosomiasis, cancer, and tumor resistance have also attracted widespread interest in the scientific community. In addition, artemether, as a novel acoustic sensitizer, is gradually showing potential for application in photodynamic therapy. This paper aims to provide a comprehensive review of the chemical structure, plant origin, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects of artemether, striving to provide systematic and in-depth reference materials for researchers in related fields.

Chemical structure and physicochemical properties

Artemisinin ether is a semi-synthetic derivative of artemisinin. Its structural feature is that the olione ring of artemisinin is converted into the corresponding methyl ether alcohol, with a molecular formula of C16H26O5 and a molecular weight of 282.38. Its structure includes a sesquiterpene skeleton, an alcohol methyl ether group, and a key organic peroxide bridge ring, which is the core structural unit of its biological activity.

In terms of physicochemical properties, artemether exhibits high lipid solubility (LogP about 3.0), which helps it penetrate cell membranes and reach targets. Its polar surface area (TPSA) is 55.38 Ų, and it has 5 hydrogen bond acceptors, indicating that its molecules have a moderate balance of polarity and hydrophilicity, which is beneficial for distribution and absorption in vivo. Artemether has high blood-brain barrier permeability, suggesting its potential application in central nervous system diseases.

From a safety perspective, artemether carries a low risk of hepatotoxicity, with no significant cardiotoxicity or hERG channel inhibitory effects. The Ames mutagenic test results were negative, indicating high safety and suitability for clinical promotion. Its half-life is about 2 hours, indicating rapid metabolism in the body and the need for a reasonable dosing regimen to maintain effective concentrations.

Plant Origins and Extraction Methods

The natural precursor of artemether is artemisinin, mainly derived from Artemisia annua L., a plant in the Asteraceae family. Artemisinin was first isolated and obtained from artemisia annua by the Chinese scientist Tu Youyou's team, marking a major breakthrough in research on natural antimalarial drugs. Artemisinin content is greatly influenced by variety, planting environment, harvest time, and other factors, and is usually obtained through solvent extraction and chromatographic purification.

Artemisinin ether is a semi-synthetic product of artemisinin. Its preparation process includes a reduction reaction of artemisinin, converting the lactone ring into an alcohol, followed by methylation to form methyl ether. This process typically uses chemical reducing agents and methylation reagents, with mild conditions and high yields, making it suitable for industrial production. Compared to artemisinin, artemether has enhanced chemical stability and lipid solubility, facilitating formulation development and clinical application.

Pharmacological activity research

Antimalarial activity

The main pharmacological effect of artemether is antimalaria, especially showing significant inhibitory effects against multidrug-resistant strains of Plasmodium falciparum. Its mechanism of action relies on the cleavage of peroxide bridge rings, generating free radicals and reactive oxygen species, which damage the cell membranes and proteins of malaria parasites, leading to parasite death. Artemether is often used in combination with drugs such as benflutoxin to form artemisinin combination therapies (ACTs), effectively delaying the development of resistance and improving treatment success rates.

Neurotoxicity and neuroprotective effects

Artemether has certain neurotoxicity, mainly manifesting as damage to the nervous system at high doses. However, at moderate doses, artemether demonstrates neuroprotective potential and may alleviate nerve damage by modulating oxidative stress and inflammatory responses. Its high blood-brain barrier permeability provides a theoretical basis for its application in neurological diseases.

It has anti-schistosomiasis activity

Research shows that artemether has an inhibitory effect on schistosomiasis parasites, interfering with their development and survival and reducing pathological damage caused by infection. This provides new drug candidates for the treatment of schistosomiasis.

Anticancer and antitumor activity

Artemether exhibits antitumor activity across various cancer models, involving multiple mechanisms such as cell proliferation inhibition, apoptosis induction, angiogenesis inhibition, and regulation of the tumor microenvironment. Its characteristics as a sensitizer give it unique advantages in photodynamic therapy, enhancing tumor cells' sensitivity to photosensitization and improving treatment outcomes.

Mechanism of action and molecular targets

The biological activity of artemether mainly depends on its unique organic peroxide structure, which can generate free radicals within parasites and tumor cells, causing cell damage and death. Its mechanism of action involves multiple molecular targets and signaling pathways, including:

• PTPN1 (protein tyrosine phosphatase 1B): Artemether regulates PTPN1 activity, affects cellular metabolism and signal transduction, and participates in the regulation of hyperlipidemia and metabolic disease pathological processes.
• STAT3 (Signal Transduction and Transcription Activator 3): Artemether can inhibit STAT3 phosphorylation, block its mediated pro-cancer signaling pathway, and exert antitumor effects.
• ABCB1 (P-glycoprotein): By inhibiting ABCB1, artemether can reverse multidrug resistance and enhance intracellular accumulation of chemotherapy drugs.
• IDH1 (isocitrate dehydrogenase 1): regulates cellular metabolism; artemether's effect on IDH1 may mediate its antitumor activity.
• NFE2L2 (nuclear factor E2-related factor 2): As a key regulator of oxidative stress responses, artemether modulates cellular antioxidant defenses by activating the NFE2L2 signaling pathway.
• TOP1 (Topoisomerase I): Artemether may affect DNA topology and interfere with cell proliferation.
• HIF1A (hypoxia-inducing factor 1α): Regulates tumor cells adapting to hypoxic environments; artemether's regulation helps suppress tumor progression.
• HSD11B1 (11β-hydroxysteroid dehydrogenase 1) and NR1H4 (farnesol X receptor): involved in lipid metabolism and inflammatory responses, artemether regulates metabolic balance through these targets.
• SIRT1 (Silencing Information Regulatory Factor 2-related enzyme 1): Regulates cell lifespan and metabolism. Activation of SIRT1 by artemether helps achieve its multiple pharmacological effects.

Druggability evaluation and pharmacokinetics

Artemether has excellent druggability, complies with Lipinski's rules, and has good oral bioavailability and in vivo distribution characteristics. Its molecular weight is moderate, with good lipid solubility and polarity, facilitating penetration of cell membranes and the blood-brain barrier.

Pharmacokinetic studies show that artemether is rapidly absorbed orally, with a plasma half-life of about 2 hours, indicating rapid metabolism in the body and requiring reasonable dosing and frequency to maintain effective concentrations. Its main metabolic pathway is hepatic metabolism, with relatively high safety of metabolites and low risk of hepatotoxicity.

In terms of safety evaluation, artemether showed no significant cardiotoxicity, did not inhibit hERG potassium channels, and the Ames mutagenic test was negative, indicating a low genotoxicity risk. The risk of hepatotoxicity is also low, making it suitable for long-term clinical use.

Prospects and outlooks for clinical applications

Artemether has achieved significant clinical results as an antimalarial drug, especially playing an irreplaceable role in treating multidrug-resistant malaria malaria strains. Artemisinin combination therapy (ACTs), which is used in combination with drugs such as benfluorosol, has become the standard treatment recommended by the World Health Organization.

In addition, artemether's potential in the treatment of neurological diseases, schistosomiasis, and tumors is becoming increasingly prominent. Research on it as a novel acoustic sensitizer expands its application prospects in photodynamic therapy and is expected to become a new treatment method for various refractory tumors.

Future research should focus on in-depth analysis of the mechanism of action of artemether, especially its regulatory network for multiple targets, as well as its pharmacodynamics and safety evaluation across different disease models. At the same time, optimizing its pharmacokinetic properties, developing novel delivery systems, and combination therapy strategies will further enhance its clinical efficacy and application scope.

Conclusion

As a semi-synthetic derivative of artemisininin, artemether has become an important drug in the field of malaria due to its unique chemical structure and diverse pharmacological activities. Its potential applications in anti-cancer, neuroprotection, and schistosomiasis resistance demonstrate broad prospects for pharmacological research of natural products. Through systematic drugability evaluation and preclinical research, artemether is expected to become an important drug for treating multiple diseases in the future. Ongoing basic and applied research will provide a solid scientific basis for its clinical promotion and new indication development.