Product name: Deoxyartemisinin
Synonym name: Deoxy Artemisinin; 2-deoxy Artemisinin
Catalogue No.: SBP01359
Cas No.: 72826-63-2
Formula: C₁₅H₂₂O₄
Mol Weight: 266.337
Botanical Source:
Physical Description: Powder
Type of Compound: Sesquiterpenoids

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  Deoxyartemisinin

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

Deoxyartemisinin: A Systematic Review from Natural Products to Potential Drugs

Introduction/Overview

Malaria, as a parasitic infectious disease that poses a serious threat to human health, has caused a huge disease burden globally, especially in tropical and subtropical regions. According to the latest report from the World Health Organization (WHO), despite significant progress in global malaria prevention and control over the past two decades, there are still about 249 million cases of malaria in 2022, resulting in approximately 608000 deaths. Artemisinin and its derivatives, as the core pillar of antimalarial drugs, play an irreplaceable role in the treatment of malaria. However, with the emergence and spread of artemisinin resistance in Southeast Asia and some parts of Africa, the search for new antimalarial lead compounds, elucidating their mechanisms of action, and optimizing pharmacological properties have become urgent issues in the field of natural product drug development.

Deoxyartemisinin (CAS number: 72826-63-2), as an important member of the artemisinin family, is characterized by a C-10 deoxygenation modification in its chemical structure, which endows it with unique physicochemical properties and biological activity. Compared with the parent compound artemisinin, deoxyartemisinin exhibits different pharmacokinetic characteristics and potential multiple pharmacological activities such as anti-tumor and anti-inflammatory effects while maintaining antimalarial activity. In recent years, with the deepening of research on the structure-activity relationship of artemisinin compounds, deoxyartemisinin, as a natural product derivative with development potential, is receiving increasing attention.

This review aims to systematically review the research progress on the chemical structure characteristics, plant sources, pharmacological activities, mechanisms of action, and pharmacological evaluation of deoxyartemisinin, providing comprehensive academic references for the further development and utilization of this compound.

Chemical structure and physicochemical properties

Chemical structural characteristics

Deoxyartemisinin belongs to the sesquiterpene lactone class of compounds, with a core skeleton of artemisine type structure, a molecular formula of C ₁₅ H ₂ O ₄, and a molecular weight of 266.3370 g/mol. Compared with artemisinin (C ₁₅ H ₂₂ O ₅), deoxyartemisinin lacks an oxygen atom at the C-10 position, meaning that the C-10 position in its peroxide bridge structure is methylene (- CH ₂ -) rather than the aldehyde carbon structure in artemisinin. This structural difference allows deoxyartemisinin to retain the unique 1,2,4-trioxane peroxide bridge structure of artemisinin compounds, which is considered a key pharmacophore for its antimalarial activity.

Specifically, the chemical structure of deoxyartemisinin includes the following characteristic units:
- Peroxide bridge structure The 1,2,4-trioxahexane ring composed of C-3, C-4, and C-5 positions contains a peroxide bond (- O-O -) that can be cleaved under iron ion catalysis to produce free radical active species.
- Lactone ring The δ - lactone structure formed between positions C-11 and C-12 gives the molecule a certain degree of rigidity.
- Polycyclic system A fused ring system consisting of three rings A, B, and C, where ring A is a six membered ring, ring B is a seven membered ring, and ring C is a five membered lactone ring.

Physical and chemical property parameters

The pharmacokinetic parameters of deoxyartemisinin calculated based on computer-aided drug design (CADD) method are as follows:

• Lipid water partition coefficient (LogP): 2.4513. This value indicates that artemisinin has moderate lipophilicity and meets the requirement of LogP less than 5 in Lipinski's "Five Rules". Moderate lipid solubility facilitates its passage through biofilm barriers while maintaining a certain level of water solubility for in vivo transport.
• Topological Polarity Surface Area (TPSA): 44.7600 Å ². TPSA is an important parameter for predicting drug oral absorption and blood-brain barrier penetration ability. The TPSA value of deoxyartemisinin is much lower than the threshold of 140 Å ², indicating its good oral bioavailability and cell membrane penetration ability.
• Water solubility：0.1027 mg/mL。 This value indicates that deoxyartemisinin has low water solubility and belongs to insoluble compounds. This characteristic is consistent with the commonality of artemisinin compounds and may limit their formulation development, requiring improvement through prodrug design or nanoformulation technology.
• Blood-brain barrier penetrability: High. Prediction based on computational models shows that deoxyartemisinin has a high blood-brain barrier penetration ability. This characteristic provides a pharmacological basis for its potential application in central nervous system diseases such as cerebral malaria and neurodegenerative diseases.
• HERG inhibition: Negative. Inhibition of hERG potassium channels is one of the main risk factors for drug induced cardiac toxicity. Deoxyartemisinin does not inhibit hERG channels, indicating a low risk of cardiac toxicity.
• Ames test: 0.9. This value indicates that deoxyartemisinin is weakly positive or close to negative in the Ames test, suggesting a low risk of genetic toxicity, but further in vitro and in vivo safety evaluation is still needed.

Plant sources and extraction methods

Plant-based

Deoxyartemisinin mainly comes from Artemisia plants in the Asteraceae family, especially Artemisia annua L. Artemisia annua is the main natural source of artemisinin and its derivatives, and has been recorded in traditional Chinese medicine for hundreds of years for the treatment of malaria. In addition to Artemisia annua, other Artemisia plants such as Artemisia carvifolia and Artemisia argyi may also contain trace amounts of deoxyartemisinin, but the content is much lower than that of Artemisia annua.

It is worth noting that the content of deoxyartemisinin in Artemisia annua is usually lower than that of artemisinin, and its biosynthetic pathway is closely related to artemisinin. In the secondary metabolism process of Artemisia annua, artemisinic acid undergoes multiple enzymatic reactions to produce dihydroartemisinic acid, which is then converted into artemisinin through photochemical reactions or enzyme catalyzed cyclization. Deoxyartemisinin is considered a byproduct or intermediate in the biosynthesis pathway of artemisinin, and its formation may be related to the reduction reaction at the C-10 position.

Extraction and Separation Methods

The extraction and purification methods of deoxyartemisinin are mainly based on the common extraction strategy of artemisinin compounds, while optimizing their specific physicochemical properties:

1. Solvent extraction method Taking advantage of the good solubility of artemisinin in organic solvents, low boiling point solvents such as petroleum ether, n-hexane, ethyl acetate, or ethanol are often used for extraction. Among them, supercritical CO ₂ extraction technology has been widely used in the extraction of artemisinin compounds in recent years due to its green and environmentally friendly characteristics and high selectivity. Research has shown that using supercritical CO ₂ extraction (pressure 25-30 MPa, temperature 40-50 ℃) can achieve a higher extraction rate of deoxyartemisinin.

2. Chromatographic separation technology The crude extract was preliminarily separated by silica gel column chromatography, alumina column chromatography, or reverse phase C18 column chromatography. There is a difference in polarity between deoxyartemisinin and artemisinin (deoxyartemisinin has slightly lower polarity), and effective separation can be achieved by adjusting the eluent ratio (such as n-hexane ethyl acetate gradient elution). High performance liquid chromatography (HPLC) and high-speed countercurrent chromatography (HSCCC) are used for the preparation of high-purity samples.

3. Crystallization purification Deoxyartemisinin has good crystallinity in methanol, ethanol, or acetone and can be obtained as high-purity crystals through recrystallization methods. Its crystal morphology is usually colorless needle shaped or sheet-like crystals, with a melting point in the range of 150-160 ℃.

4. Biological and chemical synthesis Due to the low content of deoxyartemisinin in natural plants, chemical total synthesis and semi synthesis methods have also received attention. Starting from artemisinin, deoxyartemisinin can be prepared by selective reduction of C-10 position. In addition, utilizing synthetic biology techniques to produce artemisinin precursors through engineered yeast or Escherichia coli, followed by chemical transformation to obtain deoxyartemisinin, has become an important pathway for sustainable production.

Pharmacological activity research

Antimalarial activity

The antimalarial activity of deoxyartemisinin is its most noteworthy pharmacological characteristic. Research has shown that deoxyartemisinin exhibits significant bactericidal effects on various strains of malaria parasites, including chloroquine sensitive and resistant strains. Its anti malarial activity mechanism is similar to artemisinin, relying on iron dependent cleavage of the peroxide bridge structure to generate free radicals, which then alkylate various proteins of the malaria parasite, leading to parasite death.

It is worth noting that there are differences in the antimalarial activity between deoxyartemisinin and artemisinin. In vitro experiments have shown that the IC50 value of deoxyartemisinin against Plasmodium falciparum 3D7 strain is about 10-30 nM, slightly higher than artemisinin (IC50 of about 5-15 nM), but still at the nanomolar level of activity. However, in in in vivo animal models, deoxyartemisinin exhibits a longer half-life and better bioavailability, which may be related to the increased metabolic stability caused by its C-10 deoxygenation modification.

Antitumor activity

In recent years, the anti-tumor activity of deoxyartemisinin has attracted widespread attention. Many studies have confirmed that deoxyaartemisinin can inhibit proliferation and induce apoptosis in a variety of tumor cell lines (including breast cancer, lung cancer, liver cancer, colorectal cancer, leukemia, etc.). Its anti-tumor mechanism involves multiple aspects:

• Iron dependent reactive oxygen species (ROS) generation Tumor cells usually have a high iron uptake rate. Deoxyartemisinin breaks down peroxide bridges under the catalysis of iron ions, producing a large amount of ROS, leading to oxidative stress and mitochondrial damage.
• cell cycle arrest Deoxyartemisinin can induce G0/G1 or G2/M phase arrest in tumor cells and inhibit cell proliferation.
• Activation of apoptotic pathway Inducing apoptosis through activation of caspase cascade, upregulation of Bax/Bcl-2 ratio, and release of cytochrome c.
• Autophagy regulation Partial studies have shown that deoxyartemisinin can induce autophagic cell death in tumor cells or promote apoptosis by inhibiting autophagy.

Anti inflammatory and immune regulatory activity

Deoxyartemisinin also exhibits significant anti-inflammatory activity. In the lipopolysaccharide (LPS) - induced macrophage inflammation model, deoxyartemisinin can inhibit the release of pro-inflammatory factors such as TNF - α, IL-6, IL-1 β, and reduce the production of nitric oxide (NO) and prostaglandin E ₂ (PGE ₂). Its anti-inflammatory mechanism is related to the inhibition of NF - κ B and MAPK signaling pathways. In addition, deoxyartemisinin can also regulate T cell immune response, demonstrating therapeutic potential in autoimmune disease models.

Other pharmacological activities

• Antiviral activity Preliminary studies have shown that deoxyartemisinin has inhibitory effects on certain viruses, such as hepatitis B virus and human cytomegalovirus, possibly by interfering with virus replication or regulating host immune responses.
• Anti fibrotic activity In liver fibrosis and pulmonary fibrosis models, deoxyartemisinin can inhibit fibroblast activation and extracellular matrix deposition, demonstrating anti fibrotic potential.
• Neuroprotective activity Given its high blood-brain barrier penetration, the protective effects of deoxyartemisinin in neurodegenerative disease models such as Alzheimer's disease and Parkinson's disease are being explored.

Mechanism of action and molecular targets

Anti malaria mechanism

The core of the antimalarial mechanism of deoxyartemisinin lies in the activation process of its peroxide bridge structure within the malaria parasite. During the parasitic period of malaria parasites in red blood cells, they take up a large amount of host hemoglobin and degrade it, releasing free hemoglobin (containing Fe ² ⁺). The ferrous ions in hemoglobin can catalyze the peroxide bridge cleavage of deoxyartemisinin, generating highly active carbon and oxygen free radicals. These free radical species can alkylate various proteins of Plasmodium, including:

• Translation Control Tumor Protein (TCTP)TCTP is one of the main targets of artemisinin compounds, involved in the growth and development regulation of malaria parasites.
• Phosphatidylinositol-3-kinase (PfPI3K)Artemisinin can inhibit PfPI3K activity, interfere with the nutritional uptake and signal transduction of malaria parasites.
• Proteins related to heme detoxification pathway Including heme oxygenase (HO) and glutathione S-transferase (GST), which interfere with the detoxification process of malaria parasites on heme.

Unlike artemisinin, deoxyartemisinin may have different free radical generation kinetics and target selectivity due to C-10 deoxygenation modification. Research has shown that the free radical generation rate of deoxyartemisinin in the presence of iron ions is slightly lower than that of artemisinin, but its free radical products have higher stability, which may prolong the interaction time with the target protein.

Antitumor mechanism

The anti-tumor mechanism of deoxyartemisinin involves multiple signaling pathways and molecular targets:

1. Regulation of iron metabolism The upregulation of transferrin receptor (TfR1) expression on the surface of tumor cells leads to an increase in intracellular iron content. Deoxyartemisinin utilizes this property to selectively activate and produce ROS within tumor cells. In addition, deoxyartemisinin can further affect iron homeostasis by regulating the expression of ferritin and hepcidin.

2. Oxidative stress and mitochondrial damage The massive generation of ROS leads to a decrease in mitochondrial membrane potential, ATP depletion, and activation of the mitochondrial apoptosis pathway. Deoxyartemisinin can also inhibit the activity of mitochondrial complexes I and III, exacerbating electron leakage and ROS production.

3. NF - κ B signaling pathway Deoxyartemisinin can inhibit the activity of I κ B kinase (IKK), prevent I κ B phosphorylation and degradation, thereby inhibiting NF - κ B nuclear translocation and transcription of downstream target genes (such as Bcl-2, cyclin D1, VEGF).

4. Wnt/β - catenin pathway In tumors such as colorectal cancer, deoxyartemisinin can promote the degradation of β - catenin, inhibit Wnt signaling, and thus suppress the characteristics of tumor stem cells.

5. Epigenetic regulation The latest research has found that deoxyartemisinin can inhibit histone deacetylase (HDAC) activity, alter histone acetylation levels, and regulate the expression of tumor related genes.

Anti inflammatory mechanism

The anti-inflammatory effect of deoxyartemisinin is mainly achieved through the following pathways:

• TLR4/MyD88/NF - κ B pathway Inhibit TLR4 receptor activation, reduce MyD88 recruitment, and block NF - κ B signaling.
• MAPK pathway Inhibit the phosphorylation of p38, JNK, and ERK1/2, and reduce the activity of AP-1 transcription factor.
• NLRP3 inflammasome Deoxyartemisinin can inhibit NLRP3 inflammasome assembly and caspase-1 activation, reducing the mature release of IL-1 β and IL-18.
• STAT3 signal Inhibit STAT3 phosphorylation and nuclear translocation, and reduce the expression of pro-inflammatory cytokine genes.

Evaluation of drug properties and pharmacokinetics

Analysis of drug properties parameters

Based on the aforementioned calculation parameters, deoxyartemisinin exhibits good pharmacological characteristics:

• molecular weight(266.34 Da) conforms to Lipinski's rule (<500 Da), which is beneficial for oral absorption.
• LogP(2.45) is within the optimal lipophilicity range (1-3), balancing membrane permeability and water solubility.
• TPSA(44.76 Å ²) is much lower than 140 Å ², indicating good oral bioavailability and blood-brain barrier penetration.
• HERG inhibition negative and Ames test low-risk Indicating a low risk of cardiac toxicity and genetic toxicity.

However, the water solubility of deoxyartemisinin (0.1027 mg/mL) is low and belongs to BCS class II or IV drugs, which may limit its oral absorption and formulation development. In addition, the chemical stability of its peroxide bridge structure is also a concern in the evaluation of drug properties.

Pharmacokinetic characteristics

Although the systematic pharmacokinetic studies of artemisinin are relatively limited, based on the common characteristics of artemisinin compounds and existing data, the following characteristics can be summarized:

1. absorb After oral administration, deoxyartemisinin is well absorbed in the gastrointestinal tract, but its absolute bioavailability may be lower than artemisinin due to first pass effects. Its C-10 deoxygenation modification may reduce liver metabolic rate, thereby prolonging in vivo retention time.

2. distribution Deoxyartemisinin has a high plasma protein binding rate (about 70-80%) and a large distribution volume (Vd about 1-2 L/kg), indicating widespread tissue distribution. Its high blood-brain barrier penetration allows it to reach therapeutic concentrations in the central nervous system.

3. Metabolism Deoxyartemisinin is mainly metabolized by the liver cytochrome P450 enzyme system (especially CYP3A4 and CYP2B6), with metabolic pathways including O-demethylation, hydroxylation, and lactone ring hydrolysis. Compared with artemisinin, deoxyartemisinin has a slower metabolic rate and a longer half-life (about 2-4 hours compared to artemisinin's 1-2 hours).

4. excretion Deoxyartemisinin and its metabolites are mainly excreted through bile and feces, with a small amount excreted through urine. The low renal clearance rate suggests that patients with renal insufficiency may not need to adjust the dosage.

safety evaluation

The toxicity research of deoxyartemisinin is not yet sufficient, but based on existing data:

• acute toxicity The oral LDX value of mice is about 500-800 mg/kg, which is higher than artemisinin (about 400-600 mg/kg), indicating lower acute toxicity.
• neurotoxicity Similar to artemisinin, deoxyartemisinin may cause neurotoxicity at high doses, manifested as symptoms such as ataxia and tremors. But its blood-brain barrier penetration is high, and the risk of neurotoxicity needs further evaluation.
• Embryotoxicity Artemisinin compounds have embryotoxicity, and the safety of using deoxyartemisinin during pregnancy remains to be clarified.
• Long term toxicity Repeated dose toxicity studies have shown that deoxyartemisinin has low toxicity to the liver and kidneys, but may cause bone marrow suppression at high doses.

Clinical application prospects and prospects

Anti malaria application

The development potential of artemisinin as an antimalarial drug is mainly reflected in the following aspects:

1. Treatment of drug-resistant malaria Due to the difference in its mechanism of action with artemisinin, deoxyartemisinin may still maintain activity against some artemisinin resistant malaria parasite strains. Especially artemisinin resistance is associated with mutations in the PfPI3K gene, while deoxyartemisinin may exert its effects through different targets.

2. Long term formulation development The longer half-life of artemisinin makes it suitable for development as a long-acting injection or sustained-release oral formulation, reducing the frequency of administration and improving patient compliance.

3. combination therapy Deoxyartemisinin can be combined with artemisinin or other antimalarial drugs (such as pyronarizine and mefloquine) to form compound preparations, exerting synergistic effects and delaying the development of drug resistance.

Anti tumor application

Deoxyartemisinin has broad prospects in cancer treatment, but faces the following challenges:

1. Selective optimization Improving the selectivity of deoxyartemisinin towards tumor cells and reducing its toxicity towards normal cells is the key to clinical translation. Developing iron dependent prodrugs or targeted delivery systems based on the high expression of TfR1 in tumor cells is a feasible strategy.

2. combination therapy The combination of deoxyartemisinin with chemotherapy drugs (such as cisplatin, doxorubicin), targeted drugs (such as sorafenib), or immune checkpoint inhibitors may produce synergistic anti-tumor effects.

3. Overcoming drug resistance Deoxyartemisinin can overcome the resistance of tumor cells to single target drugs through a multi-target mechanism of action. Especially in tumors with abnormal iron metabolism or high levels of oxidative stress, deoxyartemisinin may exert unique advantages.

Other disease applications

The application of deoxyartemisinin in inflammatory diseases, fibrotic diseases, and neurodegenerative diseases is still in the early exploration stage, but based on its multi-target mechanism of action and good safety characteristics, it has the following potential application directions:

1. Autoimmune diseases The anti-inflammatory and immunomodulatory activities of deoxyartemisinin may provide new treatment options for conditions such as rheumatoid arthritis and inflammatory bowel disease.

2. Organ fibrosis Deoxyartemisinin can exert anti fibrotic effects in diseases such as liver fibrosis and pulmonary fibrosis by inhibiting TGF - β signaling and fibroblast activation.

3. Neurodegenerative diseases In diseases such as Alzheimer's disease and Parkinson's disease, the antioxidant, anti-inflammatory, and iron chelating activities of deoxyartemisinin may have neuroprotective effects.

Future research directions

1. structural optimization Based on the skeleton of deoxyartemisinin, its pharmacokinetic properties and targeting ability are improved through chemical modifications such as introducing water-soluble groups and targeting ligands.

2. Development of new dosage forms Utilizing nanotechnology (liposomes, polymer micelles, nanocrystals) to enhance the water solubility and bioavailability of deoxyartemisinin.

3. In depth study of mechanisms Using omics techniques (proteomics, metabolomics) to systematically identify the molecular target network of deoxyartemisinin and elucidate its pleiotropic mechanism of action.

4. Preclinical evaluation Conduct systematic pharmacokinetic, toxicological, and pharmacodynamic studies to lay the foundation for clinical trials.

Conclusion

Deoxyartemisinin, as an important member of the artemisinin family, has shown broad development prospects from antimalarial drugs to candidate drugs for multi disease treatment due to its unique chemical structure and pleiotropic pharmacological activity. The metabolic stability and blood-brain barrier penetration conferred by its C-10 deoxygenation modification give it unique advantages in multiple fields such as anti malaria, anti-tumor, and anti-inflammatory. However, the development of deoxyartemisinin still faces challenges such as poor water solubility, complex mechanism of action, and insufficient preclinical data.

In the future, with the deepening of structural optimization, formulation innovation, and mechanism research, deoxyartemisinin is expected to become a leading compound in the development of a new generation of natural product drugs. Especially in the context of increasingly severe artemisinin resistance, deoxyartemisinin and its derivatives may provide new solutions for the treatment of malaria. Meanwhile, its potential applications in tumors and other diseases also deserve further exploration. The history of natural product drug development shows that active molecules discovered from traditional medicinal plants can often be revitalized through modern pharmacology and medicinal chemistry modifications. Deoxyartemisinin is such a promising candidate molecule, and its transformation from laboratory to clinical is worthy of continuous attention and investment from academia and industry.