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| Targets |
The targets of Annonacin include mitochondrial complex I, sodium/potassium ATPase (NKA), and sarcoplasmic reticulum (SERCA) ATPase pumps. Annonacin acts as an inhibitor of mitochondrial complex I, disrupting the electron transport chain and leading to decreased ATP production. This mitochondrial inhibition results in increased oxidative stress and can lead to neurodegeneration. Annonacin also inhibits NKA and SERCA ATPase pumps, which are essential for maintaining ion gradients and calcium homeostasis. These effects contribute to the compound's cytotoxicity and potential anti-cancer activity. The compound induces apoptosis through Bax and caspase-3-related pathways.
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| ln Vitro |
In vitro, Annonacin demonstrates significant cytotoxicity against multiple cancer cell lines including ovarian, cervical, breast, bladder, and skin cancer cells. Annonacin (1-10 µg/mL; 0-72 hours) can induce cell death in various cancer cell systems and arrest cancer cells in G1 phase. Annonacin (10 µg/mL; 0-24 hours) induces apoptosis in T24 bladder cancer cells and enhances the expression of pro-apoptotic genes. In T24 cells, Annonacin (1 µg/mL) significantly reduces cell viability, with only 56.0%, 34.2%, and 35.3% of cells alive at 24, 48, and 72 hours, respectively. Western blot analysis shows that Annonacin (10 μg/mL) increases the levels of Bax and Bad while inhibiting the levels of procaspase-3.
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| ln Vivo |
In vivo, Annonacin has been evaluated in animal models. Annonacin (0-9 mg/kg; subcutaneous osmotic pump; 3 days) increases tau protein phosphorylation in R406W transgenic mice. Annonacin (85 nM/100 μL; topical application; twice weekly; 22 weeks) exhibits anti-cancer effects in a mouse model of skin tumors. The compound's ability to induce nigral and striatal neurodegeneration in rats suggests possible relevance for atypical Parkinsonism. These in vivo studies demonstrate both the potential therapeutic applications and the neurotoxic risks associated with Annonacin.
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| Enzyme Assay |
In vitro enzyme/receptor binding studies for Annonacin focus on its inhibition of mitochondrial complex I and ATPase pumps. Mitochondrial complex I activity can be measured using spectrophotometric assays that monitor NADH oxidation or oxygen consumption rates. NKA and SERCA ATPase activities can be measured using colorimetric assays that detect inorganic phosphate release from ATP hydrolysis. IC₅₀ values for enzyme inhibition are determined from dose-response curves. These methods are for research purposes only. Standard assay conditions include appropriate buffer systems, substrates, and cofactors.
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| Cell Assay |
In vitro cell-based assays for Annonacin evaluate its cytotoxicity and apoptotic effects. Cancer cell lines (e.g., T24 bladder cancer, ovarian, cervical, breast, skin cancer cells) are treated with Annonacin at various concentrations (typically 0.1-10 µg/mL) for 24-72 hours. Cell viability is assessed using MTT or CCK-8 assays. Apoptosis is measured using Annexin V/PI staining, caspase-3/7 activity assays, and Western blot analysis of Bax, Bad, and procaspase-3 levels. Cell cycle analysis is performed using propidium iodide staining and flow cytometry. Standard cell culture conditions are used with appropriate media and supplementation.
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| Animal Protocol |
In vivo animal studies for Annonacin utilize various models. R406W transgenic mice are treated with Annonacin (0-9 mg/kg; subcutaneous osmotic pump; 3 days) to study tau phosphorylation. Skin tumor mouse models are treated with Annonacin (85 nM/100 μL; topical; twice weekly; 22 weeks) to evaluate anti-cancer effects. Neurodegeneration models in rats assess the compound's effects on nigral and striatal neurons. Tissue analysis includes immunohistochemistry for tau phosphorylation, histology for neurodegeneration, and tumor measurements for anti-cancer efficacy. All procedures must comply with institutional animal care guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Annonacin are not fully characterized in publicly available literature. The compound has a molecular weight of 596.88 g/mol and is soluble in DMSO at ≥20 mg/mL (33.51 mM). Storage: 4°C, protect from light; in solvent: -80°C for 6 months, -20°C for 1 month (protect from light). The compound is for research use only. Detailed pharmacokinetic parameters would need to be determined in preclinical studies.
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| Toxicity/Toxicokinetics |
The toxicity profile of Annonacin is of significant concern due to its association with neurodegenerative diseases. Annonacin is linked to atypical Parkinsonism in regions where consumption of Annonaceae fruits is high. The compound can increase phosphorylation of tau in the brain and induce nigral and striatal neurodegeneration in rats. These neurotoxic effects are attributed to mitochondrial complex I inhibition. The compound is classified for research use only and not for human consumption. Standard safety precautions for handling neurotoxic compounds apply, including the use of personal protective equipment and working in a chemical fume hood.
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| References | |
| Additional Infomation |
Anthocyanins have been reported to be found in Goniothalamus amuyon, Goniothalamus giganteus, and other organisms with available data.
Additional information: Annonacin has the CAS number 111035-65-5 and the molecular formula C₃₅H₆₄O₇. It is a natural acetogenin found in Annona glabra (Graviola). Annonacin acts as an inhibitor of mitochondrial complex I, NKA, and SERCA ATPase pumps. The compound demonstrates cytotoxicity against multiple cancer cell lines and induces apoptosis through Bax and caspase-3-related pathways. However, Annonacin is also linked to neurodegenerative diseases including atypical Parkinsonism. The compound increases tau phosphorylation and induces neurodegeneration in animal models. This product is for research use only and is not approved for clinical or therapeutic applications. |
| Molecular Formula |
C35H64O7
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| Molecular Weight |
596.87846
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| Exact Mass |
596.465
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| CAS # |
111035-65-5
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| PubChem CID |
354398
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| Appearance |
White to off-white solid powder
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| Density |
1.0±0.1 g/cm3
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| Boiling Point |
756.2±55.0 °C at 760 mmHg
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| Flash Point |
227.0±25.0 °C
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| Vapour Pressure |
0.0±5.8 mmHg at 25°C
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| Index of Refraction |
1.506
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| LogP |
6.36
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
26
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| Heavy Atom Count |
42
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| Complexity |
726
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| Defined Atom Stereocenter Count |
7
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| SMILES |
CCCCCCCCCCCC[C@H]([C@H]1CC[C@@H](O1)[C@@H](CCCC[C@@H](CCCCC[C@H](CC2=C[C@@H](OC2=O)C)O)O)O)O
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| InChi Key |
XNODZYPOIPVPRF-CGWDHHCXSA-N
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| InChi Code |
InChI=1S/C35H64O7/c1-3-4-5-6-7-8-9-10-11-15-21-31(38)33-23-24-34(42-33)32(39)22-17-16-19-29(36)18-13-12-14-20-30(37)26-28-25-27(2)41-35(28)40/h25,27,29-34,36-39H,3-24,26H2,1-2H3/t27-,29+,30+,31+,32+,33+,34+/m0/s1
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| Chemical Name |
(2S)-2-methyl-4-[(2R,8R,13R)-2,8,13-trihydroxy-13-[(2R,5R)-5-[(1R)-1-hydroxytridecyl]oxolan-2-yl]tridecyl]-2H-furan-5-one
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6754 mL | 8.3769 mL | 16.7538 mL | |
| 5 mM | 0.3351 mL | 1.6754 mL | 3.3508 mL | |
| 10 mM | 0.1675 mL | 0.8377 mL | 1.6754 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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