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| Targets |
MutT homolog 1 (MTH1) is the primary molecular target of 3-Isomangostin, with potent inhibitory activity (IC50 = 52 nM). MTH1 is a nucleotide pool sanitization enzyme that hydrolyzes oxidized nucleotides to prevent their incorporation into DNA; its inhibition leads to oxidative DNA damage and selective cancer cell death. Additionally, 3-Isomangostin targets human aldose reductase (IC50 = 3.48 µM), an enzyme involved in the polyol pathway of glucose metabolism. The compound also inhibits acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), enzymes that hydrolyze acetylcholine and are implicated in neurodegenerative disorders. This multi-target profile suggests potential applications in oncology, metabolic disorders, and neurodegenerative disease research.
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| ln Vitro |
In cell-free enzymatic assays, 3-Isomangostin demonstrates potent inhibition of MTH1 with an IC50 of 52 nM, effectively blocking the enzyme's ability to hydrolyze oxidized guanine nucleotides. The compound also inhibits human aldose reductase with an IC50 of 3.48 µM in biochemical assays using purified enzyme preparations. For cholinesterase inhibition, 3-Isomangostin shows IC50 values of 2.36 µg/ml against AChE and 5.32 µg/ml against BChE in Ellman's colorimetric assays. The compound exhibits free radical scavenging activity in cell-free antioxidant assays. Antiplasmodial activity has been observed with IC50 values ranging from 4.71 to 11.40 µM against Plasmodium parasites in vitro. These biochemical activities collectively establish 3-Isomangostin as a multi-functional natural product with therapeutic potential. Cellular studies have demonstrated that 3-Isomangostin inhibits the growth of various cancer cell lines through MTH1 inhibition-mediated oxidative stress mechanisms. The compound shows cytotoxic effects with IC50 values of 59.9 µM and 47.4 µM against specific cell lines. By inhibiting MTH1, 3-Isomangostin allows oxidized nucleotides to accumulate and become incorporated into DNA, leading to replication stress, DNA damage, and ultimately apoptosis in cancer cells that have elevated oxidative stress levels. The compound's free radical scavenging activity may contribute to its overall cellular effects. These cellular activities support the compound's potential as an anticancer agent and warrant further investigation into its mechanism of action and therapeutic applications.
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| ln Vivo |
In vivo studies of 3-Isomangostin are limited, as the compound is primarily used as a research tool for biochemical and cellular investigations. However, given its potent MTH1 inhibitory activity and anticancer potential, it is anticipated that future in vivo studies may evaluate its efficacy in xenograft mouse models of cancer. Typical in vivo protocols for MTH1 inhibitors involve oral or intraperitoneal administration in tumor-bearing mice, with assessment of tumor growth inhibition, body weight changes, and survival outcomes. Pharmacodynamic markers such as oxidative DNA damage (8-oxo-dG levels) and MTH1 target engagement may be measured in tumor tissues. As a natural product, 3-Isomangostin may also be studied for its bioavailability and metabolic stability in animal models.
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| Enzyme Assay |
For MTH1 inhibition assays, the enzymatic activity of recombinant human MTH1 is measured using a fluorescence-based or HPLC-based assay. Purified MTH1 enzyme is incubated with varying concentrations of 3-Isomangostin (typically 0.1-100 µM) and substrate (e.g., 8-oxo-dGTP) in reaction buffer containing Tris-HCl, MgCl2, and DTT at 37°C for 30 minutes. The reaction is terminated by heat inactivation or addition of EDTA, and product formation is quantified by fluorescence detection or HPLC analysis. IC50 values are calculated by non-linear regression analysis of dose-response curves. For aldose reductase inhibition, the enzyme is incubated with DL-glyceraldehyde as substrate and NADPH as cofactor, and the decrease in NADPH absorbance at 340 nm is monitored spectrophotometrically. For cholinesterase inhibition, Ellman's method is used with acetylthiocholine or butyrylthiocholine as substrates and DTNB as chromogenic reagent.
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| Cell Assay |
For cytotoxicity assessment, cancer cells are cultured in appropriate medium (e.g., RPMI-1640 or DMEM) supplemented with 10% fetal bovine serum and antibiotics at 37°C in a 5% CO2 incubator. Cells are seeded in 96-well plates at densities of 5,000-10,000 cells per well and allowed to adhere overnight. 3-Isomangostin is dissolved in DMSO and diluted with culture medium to achieve final concentrations ranging from 0.1 to 100 µM (DMSO concentration ≤0.1%). After 48-72 hours of treatment, cell viability is assessed using MTT, CCK-8, or SRB assays. Absorbance is measured at 540-570 nm, and IC50 values are calculated from dose-response curves. For apoptosis analysis, cells may be stained with Annexin V-FITC and propidium iodide followed by flow cytometry. For MTH1-related mechanistic studies, oxidative DNA damage markers such as 8-oxo-dG can be measured by ELISA or immunocytochemistry.
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| Animal Protocol |
In vivo efficacy studies for MTH1 inhibitors typically employ murine xenograft models. Immunodeficient mice (e.g., nude or SCID) are subcutaneously implanted with 5 × 10⁶ cancer cells in the flank. When tumors reach approximately 100-200 mm³, animals are randomized into treatment groups (n = 6-10 per group). 3-Isomangostin is administered via oral gavage or intraperitoneal injection at doses determined from preliminary toxicity studies (e.g., 10-100 mg/kg). Treatment is given daily or on a scheduled basis (e.g., 5 days on, 2 days off) for 2-4 weeks. Tumor volumes are measured twice weekly using calipers, and body weights are monitored for toxicity assessment. At study termination, tumors are excised, weighed, and processed for histopathological examination and pharmacodynamic biomarker analysis (e.g., 8-oxo-dG levels, MTH1 activity). Blood samples may be collected for pharmacokinetic analysis.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for 3-Isomangostin are not extensively reported in the literature. As a natural xanthone compound with multiple hydroxyl groups, it is expected to have moderate oral bioavailability and significant first-pass metabolism. The compound's logP and polar surface area suggest moderate membrane permeability. Based on its structural features, 3-Isomangostin likely undergoes phase II metabolism via glucuronidation and sulfation, as well as phase I oxidative metabolism by CYP450 enzymes. Its plasma protein binding is anticipated to be moderate to high. Tissue distribution may be influenced by its lipophilic xanthone core, potentially allowing accumulation in lipid-rich tissues. Further pharmacokinetic studies are needed to fully characterize its absorption, distribution, metabolism, and excretion profile.
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| Toxicity/Toxicokinetics |
Toxicological data for 3-Isomangostin are limited, as the compound is primarily used as a research reagent rather than a clinical therapeutic. Based on its natural product origin and traditional use of Garcinia mangostana in folk medicine, the compound is generally considered to have moderate safety. However, at higher concentrations, xanthone derivatives may exhibit cytotoxicity and hepatotoxicity. In cell-based assays, 3-Isomangostin shows concentration-dependent cytotoxicity with IC50 values of approximately 50-60 µM against certain cancer cell lines. No acute toxicity data or organ-specific toxicity profiles have been reported. As with any research compound, appropriate safety precautions should be taken when handling 3-Isomangostin, including the use of personal protective equipment and work in a well-ventilated area.
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| References | |
| Additional Infomation |
3-Isomangoside is a flavonoid compound. It has been reported to exist in mangosteen, Garcinia Moreira, and other organisms with relevant data.
3-Isomangostin is a natural product derived from Garcinia mangostana L. (mangosteen) shell. Its IUPAC name is 1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methylbut-2-enyl)xanthen-9-one. The compound belongs to the xanthone class of polyphenols and is structurally related to mangostin and other bioactive xanthones found in mangosteen. As a MTH1 inhibitor, 3-Isomangostin represents an attractive chemical tool for studying the role of nucleotide pool sanitization in cancer biology. MTH1 inhibition has emerged as a promising anticancer strategy, as cancer cells rely on MTH1 to survive oxidative stress. The compound's additional activities against aldose reductase and cholinesterases suggest broader therapeutic potential beyond oncology. However, 3-Isomangostin has not entered clinical trials and is strictly for research use only. |
| Molecular Formula |
C24H26O6
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|---|---|
| Molecular Weight |
410.4596
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| Exact Mass |
410.172
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| CAS # |
19275-46-8
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| PubChem CID |
13873655
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
615.9±55.0 °C at 760 mmHg
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| Melting Point |
155-160ºC
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| Flash Point |
212.3±25.0 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.605
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| LogP |
5.72
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
30
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| Complexity |
683
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
KJCDBAVVDILRMP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H26O6/c1-12(2)6-7-14-19-17(10-15(25)23(14)28-5)29-18-11-16-13(8-9-24(3,4)30-16)21(26)20(18)22(19)27/h6,10-11,25-26H,7-9H2,1-5H3
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| Chemical Name |
5,9-dihydroxy-8-methoxy-2,2-dimethyl-7-(3-methylbut-2-enyl)-3,4-dihydropyrano[3,2-b]xanthen-6-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) |
DMSO : ~100 mg/mL (~243.63 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.09 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4363 mL | 12.1815 mL | 24.3629 mL | |
| 5 mM | 0.4873 mL | 2.4363 mL | 4.8726 mL | |
| 10 mM | 0.2436 mL | 1.2181 mL | 2.4363 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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