478-01-3

Basic information

• Product Name: NOBILETIN
• Synonyms: Nobiletin, froM Citrus nobilis Lour.;Chuanpi glycosides;4H-1-Benzopyran-4-one, 2-(3,4-dimethoxyphenyl)-5,6,7,8-tetramethoxy-;Nobiletin, >=98%;NOBILETIN;3',4',5,6,7,8-HEXAMETHOXYFLAVONE;Flavone, 5,6,7,8,3',4'-hexamethoxy;hexamethoxyflavone
• CAS NO: 478-01-3
• Molecular Formula: C₂₁H₂₂O₈
• Molecular Weight: 402.39
• Product Categories: chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;natural product;Inhibitors;Hexa-substituted Flavones
• Mol File: 478-01-3.mol
• Article Data: 13

Chemical Properties

• Melting Point: 136.0 to 140.0 °C
• Boiling Point: 587.9 °C at 760 mmHg
• Flash Point: 256.5 °C
• Appearance: /
• Density: 1.244 g/cm³
• Vapor Pressure: 8.39E-14mmHg at 25°C
• Refractive Index: 1.558
• Storage Temp.: -20°C
• Solubility: Soluble in DMSO (up to 10 mg/ml)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• BRN: 360887
• CAS DataBase Reference: NOBILETIN(CAS DataBase Reference)
• NIST Chemistry Reference: NOBILETIN(478-01-3)
• EPA Substance Registry System: NOBILETIN(478-01-3)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• RTECS: DJ3052200
• Hazardous Substances Data: 478-01-3(Hazardous Substances Data)

Usage

Description

Nobiletin (NOB), chemically known as 5,6,7,8,3′,4′-hexamethoxyflavone, is a dietary polymethoxylated flavonoid found in Citrus fruits, particularly in citrus peels like tangerines. It is an O-methylated flavone with a white powder form, known for its various pharmacological activities, including neuroprotection, cardiovascular protection, antimetabolic disorder, anticancer, anti-inflammation, and antioxidation. Nobiletin is a potent antioxidant with good bioavailability and has the ability to rescue bulbectomy-induced memory impairment. It has also been shown to possess circadian clock amplitude-enhancing properties and prevent metabolic syndrome in mice via a Clock gene-dependent mechanism.

Uses

Used in Pharmaceutical Applications:
NOBILETIN is used as a multifunctional pharmaceutical agent for its various pharmacological activities, including neuroprotection, cardiovascular protection, antimetabolic disorder, anticancer, anti-inflammation, and antioxidation.
Used in Anticancer Applications:
NOBILETIN is used as a matrix metalloproteinase inhibitor and an antineoplastic agent for its potential to inhibit the growth and progression of cancer cells.
Used in Drug Delivery Systems:
NOBILETIN is used as a component in drug delivery systems to improve the delivery, bioavailability, and therapeutic outcomes of various medications.
Used in Antioxidant Applications:
NOBILETIN is used as an antioxidant for its potent antioxidant properties, which can help protect cells from damage caused by free radicals.
Used in Anti-Inflammatory Applications:
NOBILETIN is used as an anti-inflammatory agent for its ability to reduce inflammation and alleviate symptoms associated with inflammatory conditions.
Used in Cardiovascular Protection:
NOBILETIN is used as a cardiovascular protective agent for its potential to lower cholesterol and atherosclerosis, and improve hyperglycemia and insulin resistance.
Used in Neuroprotection:
NOBILETIN is used as a neuroprotective agent for its ability to attenuate the effects of neuroinflammation, possess neurotrophic activity, and rescue bulbectomy-induced memory impairment.
Used in Metabolic Syndrome Prevention:
NOBILETIN is used as a preventive agent for metabolic syndrome, as it has been shown to prevent the condition in mice via a Clock gene-dependent mechanism.
Used in Bone Loss Suppression:
NOBILETIN is used as an agent to suppress bone loss, based on animal and in vitro data demonstrating its potential ability to maintain bone health.
Used in Application Industry Food and Beverage:
NOBILETIN is used as a natural additive for its antioxidant and anti-inflammatory properties, which can enhance the quality and shelf life of various food and beverage products.
Used in Application Industry Cosmetics:
NOBILETIN is used as an ingredient in the cosmetics industry for its potential benefits in skincare, such as anti-aging and anti-inflammatory effects.

Source

Nobiletin is a nonpolar polymethoxylated flavone (PMFs) found in the citrus peel of various fruits, such as tangerine. Its chemical structure is similar to tangeretin, containing the typical flavonoid structure and six methoxyl groups (one more than tangeretin).

structure and hydrogen bonding

The crystal structure study on NOB shows that the chromene and the arene rings are almost in the same plane. The C atoms of the two methoxy groups in the arene ring are also in the same plane, while the C atoms of four methoxy groups linking to the chromene ring are not in parallel. This conformational characteristic of chiral structure is indicated by the covalent bond rotation between the arene and the chromene rings and the conformational alternations of methoxy groups.

benefits

Nobiletin improved cognitive deficits and the pathological features of AD, such as Aβ pathology, hyperphosphorylation of tau, and oxidative stress, in animal models of AD. In addition, nobiletin improved motor and cognitive deficits in PD animal models. These observations suggest that nobiletin has the potential to become a novel drug for the treatment and prevention of neurodegenerative diseases such as AD and PD.

References

1) He?et al.?(2016),?The Small Molecule Nobiletin Targets the Molecular Oscillator to Enhance Circadian Rhythms and Protect against Metabolic Syndrome; Cell Metabolism,?23?610 2) Mulvihill?et al.?(2011),?Nobiletin attenuates VLDL overproduction, dyslipidemia, and atherosclerosis in mice with diet-induced insulin resistance; Diabetes?60?1446 3) Cui?et al.?(2010),?Anti-neuroinflammatory activity of nobiletin on suppression of microglial activation; Biol. Pharm. Bull.,?33?1814 4) Nagase?et al.?(2005),?Mechanism of neurotrophic action of nobiletin in PC12D cells; Biochemistry?44?13683 5) Walle (2007),?Methoxylated flavones, a superior cancer chemopreventative flavonoid subclass?;?Semin. Cancer Biol.?17?354

InChI:InChI=1/C21H22O8/c1-23-13-8-7-11(9-15(13)24-2)14-10-12(22)16-17(25-3)19(26-4)21(28-6)20(27-5)18(16)29-14/h7-10H,1-6H3

Upstream product

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• 24824-54-2 3,4-dimethoxybenzoic anhydride 
• 683278-67-3 5,8-dihydroxy-6,7-dimethoxy-2-(3,4-dimethoxyphenyl)-4-benzopyrone 
• 77-78-1 dimethyl sulfate 
• 186581-53-3 diazomethane 
• 34810-62-3 3′-methoxy-4′-hydroxy-5,6,7,8-tetramethoxyflavone 
• 333347-81-2 (1H-benzo[d][1,2,3]triazol-1-yl)(3,4-dimethoxyphenyl)methanone 
• 634-36-6 1,2,3-trimethoxybenzene 
• 21450-56-6 1,2,3,4-tetramethoxybenzene 
• 13909-75-6 1,2,3,4,5-pentamethoxybenzene 
• 5333-45-9 1,2,3,5-tetramethoxybenzene 
• 7507-98-4 1-(2-hydroxy-3,4,6-trimethoxyphenyl)ethanone 
• 7508-05-6 1-(2,3,4,6-tetramethoxyphenyl)ethanone 
• 30225-99-1 2,3,4,5-Tetramethoxyphenol 

Downstream Products

• 1178-24-1 3,3',4',5,6,7,8-heptamethoxyflavone 
• 1176-88-1 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone 
• 1370734-53-4 3-(2-(4-chlorophenyl)-2-oxoethyl)-5,6,7-trimethoxy-2-(4-methoxyphenyl)-4H-chromen-4-one 
• 1370734-54-5 ethyl 2-(2-(3,4-dimethoxyphenyl)-5,6,7-trimethoxy-4-oxo-4H-chromen-3-yl)acetate 
• 2798-20-1 gardenin B 
• 19103-54-9 5-hydroxy-4',6,7-trimethoxyflavone 
• 21763-80-4 5-desmethylsinensetin 
• 479-90-3 artemetin 
• 2174-59-6 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone 
• 74670-14-7 2',3',4',5',6'-pentamethoxyflavone 
• 70460-32-1 5,6,7,8,2',3',4',5',6'-nonamethoxyflavone 
• 91556-09-1 2,3,4,5,6-pentamethoxybenzoic acid 
• 14786-40-4 1-(2,3,4,5,6-pentamethoxyphenyl)ethan-1-one 
• 35154-55-3 3-hydroxy-5,6,7,8,3′,4′-hexamethoxyflavone 

Relevant articles and documents

Synthesis of Polymethoxyflavonoids from Hesperidin and Naringin and their Antiproliferative Activity

[Figure not available: see fulltext.] A series of polymethoxyflavonoids were synthesized via cleavage of the glycosidic bond, dehydrogenation, selective methylation, bromination, nucleophilic aromatic substitution, O-prenylation, Claisen–Schmidt aldol condensation, cyclization, and oxidation from very abundant and inexpensive natural flavonoids hesperidin and naringin. The in vitro antiproliferative activity of the synthesized compounds was evaluated against a panel of four human cancer cell lines (Aspc-1, HCT-116, HepG-2, and SUN-5) by the CellTiter-Glo assay. The results showed that some of synthesized compounds exhibited moderate to high antiproliferative activity. Among them, (2E)-1-(2-hydroxy-3,4,5,6-tetramethoxyphenyl)-3-(7-methoxy-1,3-benzodioxol-5-yl)prop-2-en-1-one was revealed to be the most active with IC50 values ranging from 10.35 to 13.89 μM against all four cancer cell lines, the IC50 value (10.35 μM) being below positive control cisplatin (12.36 μM) against HepG-2 cells.

Practical Synthesis of Polymethylated Flavones: Nobiletin and Its Desmethyl Derivatives

We present a practical synthesis of the polymethoxylated citrus flavone nobiletin that is suitable for use on a hundred gram scale. Ready availability of this compound and its derivatives will aid detailed chemical-biological investigations of their biological activities, including activation of signaling via the cAMP-dependent protein kinase A/extracellular signal-related protein kinase/cAMP response element-binding protein pathway.

Synthesis of Citrus polymethoxyflavonoids and their antiproliferative activities on Hela cells

Abstract: A series of polymethoxyflavonoids (3–16) were synthesized through dehydrogenation, O-methylation, glycoside hydrolysis, bromination, microwave-assisted aromatic nucleophilic substitution, dimethyldioxirane oxidation and regioselective demethylation, starting from abundant and inexpensive natural sources naringin and hesperidin. All the synthetic compounds were test for antiproliferative activities on human cervical carcinoma Hela cell line by the standard CCK-8 assay, the result showed that most of the target compounds exhibited moderate to potent antiproliferative activities on Hela cells comparable with the positive control cis-Platin. Among them, 5-hydroxypolymethoxy flavonoid 13 showed the strongest activity (IC50 0.791 μM). Graphical Abstract: [InlineMediaObject not available: see fulltext.].