Structure of α-mangostin
CAS No.: 6147-11-1
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
alpha-Mangostin is a dietary xanthone with broad biological activities, such as antioxidant, anti-allergic, antiviral, antibacterial, anti-inflammatory and anticancer effects. It is an inhibitor of mutant IDH1 (IDH1-R132H) with a Ki of 2.85 μM.
Synonyms: alpha-Mangostin; NSC 27593; NSC 30552
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Discovery of Polyphenolic Natural Products as SARS-CoV-2 Mpro Inhibitors for COVID-19
Krueger, Nadine ; Kronenberger, Thales ; Xie, Hang ; Rocha, Cheila ; Poehlmann, Stefan ; Su, Haixia , et al.
Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the development of direct-acting antiviral drugs due to the coronavirus disease 2019 (COVID-19) pandemic. The main protease of SARS-CoV-2 is a crucial enzyme that breaks down polyproteins synthesized from the viral RNA, making it a validated target for the development of SARS-CoV-2 therapeutics. New chem. phenotypes are frequently discovered in natural goods. In the current study, we used a fluorogenic assay to test a variety of natural products for their ability to inhibit SARS-CoV-2 Mpro. Several compounds were discovered to inhibit Mpro at low micromolar concentrations It was possible to crystallize robinetin together with SARS-CoV-2 Mpro, and the X-ray structure revealed covalent interaction with the protease's catalytic Cys145 site. Selected potent mols. also exhibited antiviral properties without cytotoxicity. Some of these powerful inhibitors might be utilized as lead compounds for future COVID-19 research.
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Keywords: COVID-19 ; antivirals ; coronavirus ; covalent drugs ; dynamic light scattering ; inhibitors ; main protease ; natural products
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Purchased from AmBeed: 20554-84-1 ; 18524-94-2 ; 568-73-0 ; 989-51-5 ; 484-12-8 ; 86404-04-8 ; 491-70-3 ; 2752-65-0 ; 6147-11-1 ; 10083-24-6 ; 50-81-7 ; 2752-65-0 ; 522-12-3 ; 529-44-2 ; 529-53-3 ; 546-43-0 ; 501-36-0 ; 28957-04-2 ; 4674-50-4 ; 477-43-0 ; 553-21-9 ; 96829-58-2 ; 96574-01-5 ; 20283-92-5 ; 490-31-3 ; 17912-87-7 ; 520-31-0 ; 86404-04-8
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CAS No. : | 6147-11-1 |
Formula : | C24H26O6 |
M.W : | 410.46 |
SMILES Code : | O=C1C2=C(OC3=C1C(C/C=C(C)\C)=C(OC)C(O)=C3)C=C(O)C(C/C=C(C)\C)=C2O |
Synonyms : |
alpha-Mangostin; NSC 27593; NSC 30552
|
MDL No. : | MFCD00135200 |
InChI Key : | GNRIZKKCNOBBMO-UHFFFAOYSA-N |
Pubchem ID : | 5281650 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H413 |
Precautionary Statements: | P501-P273-P270-P264-P301+P312+P330 |
In Vitro:
Cell Line
|
Concentration | Treated Time | Description | References |
MGC803 cells | 12.46 μM | 72 hours | α-MGT significantly inhibited the proliferation of MGC803 cells | PMC6981176 |
HepG2 cells | 10.94 μM | 72 hours | α-MGT significantly inhibited the proliferation of HepG2 cells | PMC6981176 |
Huh-7 cells | 14.49 μM | 72 hours | α-MGT significantly inhibited the proliferation of Huh-7 cells | PMC6981176 |
SMMC-7721 cells | 13.22 μM | 72 hours | α-MGT significantly inhibited the proliferation of SMMC-7721 cells | PMC6981176 |
SK-Hep-1 cells | 9.44 μM | 72 hours | α-MGT significantly inhibited the proliferation of SK-Hep-1 cells | PMC6981176 |
MDA-MB-468 cells | 13.06 μM | 72 hours | α-MGT significantly inhibited the proliferation of MDA-MB-468 cells | PMC6981176 |
HCT116 cells | 14.31 μM | 72 hours | α-MGT significantly inhibited the proliferation of HCT116 cells | PMC6981176 |
Primary microglia | 400 ng/mL | 24 hours | α-mangostin restored metabolic balance through AMPK activation, enhancing microglial phagocytosis and degradation of misfolded proteins. | PMC9978858 |
BV-2 cells | 400 ng/mL | 24 hours | α-mangostin reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. | PMC9978858 |
NIH3T3 cells | 27.8 μM | 24 hours | Reverse the expression of CAFs related proteins including α-SMA, FAP and fibronectin, and decrease pSmad2/3 expression | PMC6992734 |
U2OS cells | 2.5-40 μmol/L | 0.5-24 hours | Induced pyroptosis, confirmed by Annexin V-PI double staining, LDH release assay, and immunoblot analysis of GSDME cleavage. | PMC11786723 |
Vancomycin-resistant Enterococcus faecium CAU 369 | 2 µg/mL | 18 hours | Evaluate antibacterial activity, showing rapid bactericidal effects | PMC8336499 |
MDA-MB231 cells | 20 μM | 24 hours | To evaluate the effect of α-mangostin on cell viability, results showed significant reduction in cell viability after 24 hours | PMC3121600 |
U87 cells | 0.156 μg/ml | 72 hours | Inhibited cellular activity and promoted apoptosis | PMC7595144 |
C6 cells | 0.156 μg/ml | 48 hours | Inhibited cellular activity and promoted apoptosis | PMC7595144 |
Gl261 cells | 0.156 μg/ml | 48 hours | Inhibited cellular activity and promoted apoptosis | PMC7595144 |
BJMC3879luc2 cells | 12 μM | 24 hours | To evaluate the effect of α-mangostin on cell viability, results showed significant reduction in cell viability after 24 and 48 hours | PMC3121600 |
In Vivo:
Species
|
Animal Model
|
Administration | Dosage | Frequency | Description | References |
C57BL/6 mice | Alzheimer’s disease model mice (3/C2TG) and Parkinson’s disease model mice | Intravenous injection | 1 mg/kg | Once daily for one month | Nanoformulated α-mangostin efficiently delivered to microglia, relieved their reactive status and rejuvenated their capacity to clear misfolded proteins, significantly alleviating neuropathological changes in both Alzheimer’s disease and Parkinson’s disease model mice. | PMC9978858 |
Nude mice | HepG2 or SK-Hep-1 xenograft model | Intraperitoneal injection | 50 mg/kg | Once per day for 20 days | α-MGT significantly inhibited the growth of HCC tumors in terms of tumor volume and tumor weight | PMC6981176 |
C57BL/6 mice | Orthotopic KPC1199 pancreatic ductal adenocarcinoma model | Intravenous injection | 13.9 mg/kg | Administered every other day for 1 week | Nano-sapper reverses the abnormal activation of CAFs, decreases collagen deposition, normalizes intratumoral vasculatures, and stimulates the expression of lymphocyte-recruiting chemoattractants in situ, promoting CTLs infiltration, inducing intratumoral tertiary lymphoid structures, thus reshaping tumor microenvironment and potentiating checkpoint inhibitor against IET | PMC6992734 |
Mouse | Osteosarcoma xenograft model | Oral | 50 or 100 mg/kg | Significantly inhibited tumor growth, activated antitumor immune response, upregulated CD8, CD56, and F4/80 expression. | PMC11786723 | |
BALB/c mice | Skin wound infection model | Topical administration | 2 mg/kg | Single dose, observed for 15 days | Evaluate therapeutic efficacy, significantly reducing bacterial loads | PMC8336499 |
BALB/c mice | Metastatic mammary cancer model | Subcutaneously implanted mini-osmotic pumps | 10 and 20 mg/kg/day | Daily administration for 6 weeks | To evaluate the effect of α-mangostin on tumor growth and lymph node metastasis, results showed significantly higher survival rates and reduced tumor volume and lymph node metastasis in the 20 mg/kg/day group | PMC3121600 |
Bio Calculators | ||||
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1mg | 5mg | 10mg |
1 mM 5 mM 10 mM |
2.44mL 0.49mL 0.24mL |
12.18mL 2.44mL 1.22mL |
24.36mL 4.87mL 2.44mL |
Tags: alpha-Mangostin | α-Mangostin | Reactive Oxygen Species | Apoptosis | IDH1-R132H inhibitor | isocitrate dehydrogenase 1 | R132H mutation | 2-hydroxyglutarate | IDH1-mutant | Bacterial | Fungal | Virus Protease | 6147-11-1
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