KR101087119B1 - Novel cromendiol derivative compounds, a preparation method thereof and composition comprising the same - Google Patents

Abstract

The present invention relates to a novel chromatediol derivative compound having an active oxygen scavenging activity, a method for preparing the same, and a composition comprising the same, and more particularly, to a novel chromatediol derivative compound represented by the formula (1) and a method for preparing the same. In addition, the present invention relates to a composition for preventing and treating diseases caused by excessive accumulation of active oxygen including the same as an active ingredient.

[Formula 1]

The compound of the present invention is excellent in active oxygen scavenging activity and can be usefully used in medicines, cosmetics, health functional foods and the like for the prevention and treatment of diseases caused by excessive accumulation of antioxidants and / or active oxygen.

Free radicals, chromatindiol derivatives, scavenging activity, antioxidant

Description

Novel cromendiol derivative compounds, a preparation method according to the present invention and composition comprising the same

The present invention relates to a novel chromatediol derivative compound having an active oxygen scavenging activity, a method for preparing the same, and a composition comprising the same, and more particularly, a novel chromatediol derivate compound represented by Formula 1 and a method for preparing the same. And it relates to a composition for the prevention and treatment of diseases caused by excessive accumulation of free radicals containing it as an active ingredient.

Oxygen free radicals contain unpaired electrons and are highly reactive with surrounding materials and are produced through a variety of developmental pathways. These free radicals are known to occur as a result of oxidation-reduction or aging through metabolism in the human body (Kikola Getoff, Radiation Physics and Chemistry, 76, 1577-1586, 2007). In addition, it occurs during food storage and reacts with fats present in foods, causing rancidity and thus degrading the quality (Laura Zambonin et al , Free Radical Biology & Medicine, 40, 1549-1556, 2006).

In particular, the chain reaction with unsaturated fatty acids causes fat to decay, reducing the flavor and value of the food. Oxidation of fat components through the chain reaction of active oxygen continues to cause rancidity caused by active oxygen. Continue in a chain.

Vitamins C and E, phenolic compounds including flavonos, substances containing sulfur, and various enzymes are antioxidants existing in nature and have the effect of inhibiting free radicals (S. Kaiser et al , Arch. Biochem. Biophys., 277 (1), 101-108, 1990).

Ingestion of various antioxidants induces free radical scavenging activity generated through various pathways in the human body, and the use of an appropriate amount of antioxidants removes free radicals generated during storage of food, preventing various diseases in the body. And improves food preservation.

External influences such as drinking, smoking, and ultraviolet radiation, and free radicals generated during metabolism and aging of the body, react with various proteins and fats to induce oxidative stress (R. Stocker et al , Oxidative Stress: Oxidants and Antioxidants, Academic press (London, UK), 213-243, 1991), and are known to cause chronic diseases such as anemia, diabetes, kidney disease and retinopathy (K. Stadler et al , Free Radical Biology & Medicine). , 45, 866-874, 2008).

In addition, it causes oxidation of chromosomes (DNA) and is known to be one of the main causes of various cancers, degenerative diseases such as arthritis, and diseases such as vasoconstrictive heart disease (M. Valko et al , Chemico-Biological Interactions, 160). , 1-40, 2006).

Therefore, the removal of free radicals is essential for the prevention of various diseases and life-threatening cancers associated with aging.

As a method for measuring the scavenging ability of active oxygen, DPPH (1,1-Diphenyl-2-picrylhydrazyl), which contains a radical and a stable substance, is added together with an antioxidant to improve the antioxidant capacity through color change due to radical scavenging. Measurement is common (O. Bozdag-Dundar et al , Med. Chem. Res., 18, 1-7, 2009).

DPPH containing free radicals is a substance with maximum absorbance at 517 nm and appears purple when dissolved in dimethylsulfoxide (DMSO) or ethanol alone. However, when antioxidants are added, antioxidants receive electrons from DPPH and free radicals (DPPH) are reduced, which causes the purple color to fade gradually (Bleaching effect). The degree of change in color is measured to determine the antioxidant effect of the added material.

Standards used in experiments using DPPH are vitamin C, E, and BTH (Butylated Hydroxy Toluene), and the antioxidant capacity is measured by comparing the activity as an antioxidant.

The present inventors have completed the present invention by confirming that the addition of DPPH to the derivative compound of the new chromatediol shows an excellent antioxidant effect by measuring the relative antioxidant removal effect compared to vitamin C.

After all, the main object of the present invention is to provide a novel chromatindiol derivative compound having an active oxygen scavenging activity, a preparation method thereof and a composition comprising the same.

In order to achieve the above object, the present invention provides a novel chromatediol derivative compound represented by the following formula (1) and a method for preparing the same.

[Formula 1]

In another aspect, the present invention provides a composition for the prevention and treatment of diseases caused by excessive accumulation of active oxygen containing the compound of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

In the present invention, the disease caused by the accumulation of excess oxygen is brain disease, ischemia, heart disease, autoimmune disease, liver disease, arteriosclerosis, skin disease, hyperlipidemia, diabetes, skin disease, rheumatism, inflammation, cancer And aging.

The chromatindiol derivative compounds of the present invention have an active oxygen scavenging activity that inhibits naturally occurring free radicals. As a result, the present invention can be usefully used in medicines, cosmetics, health foods, etc. for the prevention and treatment of diseases caused by excessive accumulation of antioxidants and / or active oxygen having an active oxygen scavenging activity (or scavenging function) Can be.

Hereinafter, the present invention will be described in detail.

The present invention provides novel chromemendiol derivative compounds.

In the present invention, the novel chromatediol derivative compound is a particularly preferred group of compounds (E) -2- (4-hydroxyphenly) -4- (2-phenylhydrazono) -3 which is a compound represented by the following [Formula 1]. , 4-dihydro-2H-chromene-5,7-diol or pharmaceutically acceptable salts thereof.

[Formula 1]

The chromatediol derivative compound of the present invention is characterized in that it has an active oxygen scavenging activity, and also has a DPPH (1,1-Diphenyl-2-picrylhydrazyl) scavenging activity. Therefore, the chromatediol derivative compound of the present invention can be used as an antioxidant.

The present invention also provides a pharmaceutical composition for preventing and treating diseases caused by excessive accumulation of active oxygen including the compound of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

In the present invention, the disease caused by excessive accumulation of free radicals is a brain disease, such as stroke, Parkinson's disease, Alzheimer's disease, ischemia, heart disease, autoimmune disease, liver disease, arteriosclerosis, skin disease, hyperlipidemia, diabetes , Skin diseases, rheumatism, inflammation, cancer and aging.

The compound of the present invention represented by the above [Formula 1] may be prepared with pharmaceutically acceptable salts and solvates according to conventional methods in the art.

As salts are acid addition salts formed with pharmaceutically acceptable free acids. Acid addition salts are prepared by conventional methods, for example, by dissolving a compound in an excess of aqueous acid solution and precipitating the salt using a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. Equal molar amounts of the compound and acid or alcohol (eg, glycol monomethyl ether) in water may be heated and then the mixture is evaporated to dryness or the precipitated salts may be suction filtered.

In this case, an organic acid and an inorganic acid may be used as the free acid, and hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, and the like may be used as the inorganic acid, and methanesulfonic acid, p -toluenesulfonic acid, acetic acid, trifluoroacetic acid, Citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, glycolic acid gluconic acid), galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid, and the like.

In addition, bases can be used to make pharmaceutically acceptable metal salts. An alkali metal or alkaline earth metal salt is obtained by, for example, dissolving a compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and then evaporating and drying the filtrate. At this time, as the metal salt, it is particularly suitable to prepare sodium, potassium or calcium salt, and the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (for example, silver nitrate).

Pharmaceutically acceptable salts of Formula 1 include salts of acidic or basic groups which may be present in compounds of Formula 1 unless otherwise indicated. For example, pharmaceutically acceptable salts include sodium, calcium and potassium salts of the hydroxy group, and other pharmaceutically acceptable salts of the amino group include hydrobromide, sulfates, hydrosulfates, phosphates, hydrogen phosphates, dihydrogen Phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p -toluenesulfonate (tosylate) salts, and methods or processes for preparing salts known in the art It can be prepared through.

In addition, the present invention provides a method for preparing a chromatediol derivative compound of Formula 1.

In the present invention, the compound of Formula 1 may be chemically synthesized by the method shown in Scheme 1 below, but is not limited thereto, and may be variously prepared using other organic synthesis reactions known in the art. have.

In a preferred embodiment, the present invention is naringenin as a starting material, completely dissolved in ethanol, and then added acetic acid and phenylhydrazine (Phenyl hydrazine) to maintain 80 to 120 ℃, preferably 100 ± 5 ℃ 3 to 20 Compound (E) -2- (4-hydroxyphenly) -4- (2-phenylhydrazono) -3,4-dihydro represented by Chemical Formula 1, which is prepared by heating and stirring for 12 hours to 20 hours. Provided is a method for preparing -2H-chromene-5,7-diol.

In this case, the ethanol is preferably adjusted by using a mass ratio based on the amount (3 ml) capable of completely dissolving 0.1 g of naringenin, and the acetic acid also maintains acid conditions when reacting 0.1 g of naringenin It is preferable to adjust the amount using the mass ratio based on the amount (0.1 mL).

The naringenin and phenylhydrazine may be added in a ratio of 1: 1 based on the molar ratio.

After completion of the reaction, the solution is separated, washed, and then purified by gas chromatography, high performance liquid chromatography, liquid chromatography, or ion exchange. The compound of formula 1 may be obtained by chromatography or gel chromatography.

The compound of Formula 1 according to the present invention prepared as described above has excellent solubility in organic solvents such as alcohol, ethyl acetate, DMSO, THF, and the like, and thus can be used as an antioxidant (or antioxidant). .

In another aspect, the present invention provides a pharmaceutical composition for the prevention and treatment of diseases caused by excessive accumulation of active oxygen containing a compound of Formula 1 as an active ingredient, including a pharmaceutically acceptable carrier.

Pharmaceutical compositions comprising a compound of the present invention may further comprise a suitable carrier, excipient or diluent according to conventional methods.

Carriers, excipients and diluents that may be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose And methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

Pharmaceutical compositions comprising a compound of the present invention are each formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, or the like, external preparations, suppositories, or sterile injectable solutions according to conventional methods. Can be used.

Specifically, when formulated, it may be prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrating agents, surfactants, etc. which are commonly used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient in the compound, for example, starch, calcium carbonate, sucrose. ), Lactose, gelatin and the like can be mixed. In addition to simple excipients, lubricants such as magnesium stearate, talc may also be used. Liquid preparations for oral use include suspensions, solvents, emulsions, and syrups.In addition to the commonly used simple diluents, water and liquid parazin, various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc. May be included. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

Preferred dosages of the compounds of the present invention will be appropriately selected by those skilled in the art depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration. However, for the desired effect, the compounds of the present invention may be administered in divided doses of 10 to 500 mg once to several times daily. The compound of the present invention in the composition should be present in an amount of 0.01 to 50% by weight relative to the total weight of the total composition.

In addition, the pharmaceutical dosage forms of the compounds of the present invention may be used in the form of their pharmaceutically acceptable salts, and may be used alone or in combination with other pharmaceutically active compounds, as well as in a suitable collection.

The pharmaceutical composition of the present invention can be administered to mammals such as mice, mice, livestock, humans, etc. by various routes, and all modes of administration can be expected, for example, oral, rectal or intravenous, muscular, subcutaneous. , Intrauterine dural or intracerebroventricular injection.

In another aspect, the present invention provides a cosmetic composition for preventing aging caused by the accumulation of the active oxygen in excess of the compound of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

When using the compound of Formula 1 according to the present invention as a cosmetic, including conventional cosmetic base components in addition to the compound, for example, conventional containing agents such as stabilizers, solubilizers, pigments and fragrances, and carriers It may include. In addition, the cosmetics may be prepared in any formulation conventionally prepared in the art, and are not particularly limited, for example, cosmetic lotions, essences, lotions, pastes, surfactant-containing cleansing, creams, packs, gels, ointments, It may have a formulation of powder, patch or spray (spray).

In case the formulation of the cosmetic composition is a paste, cream or gel, the carrier component is animal oil, vegetable oil, wax, paraffin, starch, trakant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc and zinc oxide. One or more selected from the group can be used, and when the formulation is a lotion, an essence, a solvent, a solubilizing agent or an emulsifying agent is used as the carrier component, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, One or more selected from the group consisting of benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils, glycerol aliphatic esters, polyethylene glycols, fatty acid esters of sorbitan, and the like can be used.

In addition, when the formulation of the cosmetic composition is a powder or spray, one or more selected from the group consisting of lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, etc. may be used as a carrier component, and in particular, spray May further comprise propellants such as chlorofluorohydrocarbons, propane / butane or dimethyl ether. In addition, in the case where the formulation of the cosmetic composition is a surfactant-containing cleansing agent, as a carrier component, an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, isethionate, an imidazolinium derivative, methyl taurate, sarcosinate, One or more selected from the group consisting of fatty acid amide ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, ethoxylated glycerol fatty acid esters, and the like can be used.

At this time, the compound in the cosmetic is added at 0.01 to 50% by weight, preferably 0.01 to 30% by weight of the total weight.

In addition, the present invention provides a health functional food composition for the prevention and improvement of the symptoms caused by the disease caused by excessive accumulation of active oxygen containing the compound of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. .

Examples of the food to which the compound of the present invention can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods. It may also be added to food or beverages for the purpose of preventing cerebral disease symptoms.

At this time, the amount of the extract in the food or beverage is generally added to the functional food composition of the present invention 0.01 to 50% by weight, preferably 0.01 to 30% by weight of the total food weight, the health beverage composition is 100ml It can be added in a ratio of 0.01 to 5g, preferably 0.1 to 3g on the basis of.

The health functional food of the present invention includes the form of tablets, capsules, pills, liquids, and the like, and the health beverage composition of the present invention contains the compound as an essential ingredient in the indicated ratio, and there is no particular limitation on the liquid component. Like beverages may further contain various flavors or natural carbohydrates.

Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose, such as maltose, sucrose and the like, and conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and the like. Sugar alcohols such as xylitol, sorbitol, and erythritol. In addition to the above, natural flavors, taumartins, stevia extracts such as rebaudioside A, glycyrrhizin and the like and synthetic flavors, saccharin, aspartame and the like can be advantageously used as flavoring agents.

In addition to the above, the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic and natural flavors, colorants and enhancers (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and salts thereof. , Organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like. These components may be used independently or in combination, and the proportion of such additives is not so critical but is usually selected in the range of 0 to about 20 parts by weight relative to 100 parts by weight of the composition of the present invention.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these examples are for illustrative purposes only and that the scope of the present invention is not construed as being limited by these examples.

Example 1. (E) -2- (4-hydroxyphenyl) -4- (2-phenylhydrazono) -3,4-dihydro-2H-chromen-5,7-diol [(E) -2- (4-hydroxyphenyl) -4- (2-phenylhydrazono) -3,4-dihydro-2H-chromene-5,7-diol]

Argon (Ar) gas was charged into a completely dried 250 mL round bottom flask, and then naringenin (300 mg, 1.10 mmol) was dissolved in 10 mL of ethanol and a small amount of acetic acid (1 mL) was added. .

When naringenin is completely dissolved in ethanol containing a small amount of acetic acid, phenylhydrazine (Phenyl Hydrazine, 0.11 ml, 1.10 mmol) is added, and the mixture is distilled under reflux at 95-100 ° C. for 12 hours, and then a small amount of water is used to terminate the reaction. The reaction was filtered through filter paper by the addition of.

The filtered reaction product was dissolved again using methylene chloride (Methylene chloride, CH ₂ Cl ₂ ), purified by chromatography (Flash column chromatography, CH ₂ Cl ₂ / EtAOc), and a brown solid compound (323 mg, 0.89 mmol). (Yield: 80.86%).

Experimental Example 1. Confirmation of structure using nuclear magnetic resonance spectroscopy (NMR)

In order to confirm the structure of the compound prepared in Example 1, ¹ H-NMR, ¹³ C-NMR, DEPT, COZY, HMQC, and HMBC were tested. At this time, the model was using a Bruker Avance 400 Spectrometer (Karlsruhe, Germany), and dissolved in deuterium dimethyl sulfoxide (DMSO- d ₆ ) at a temperature of 298K.

For hydrogen nuclear magnetic resonance spectroscopy ( ¹ H-NMR), 32 scans were performed at 1 second intervals, and 32K data points were used. The 90-degree pulse was recorded at 9.5 seconds and the spectral width was 4789 kHz. The results are shown in FIG.

The carbon nuclear magnetic resonance spectroscopy ( ¹³ C-NMR) and the DEPT spectra use 64K data points, the 90 degree pulse is 10.5 seconds, and the spectral width is 22371 ms. The results are shown in FIG. 2.

All two-dimensional spectra (2D) used data points of 2048 for the f2 dimension and 256 data points for the f1 dimension. HMBC used 70 milliseconds (ms) for long range coupling constants.

¹ H-NMR (400 MHz) δ: 2.85 (dd, 16.96, 12.09), 3.30 (dd, 16.89, 2.87), 5.09 (dd, 11.98, 2.68), 5.94 (d, 2.27), 6.01 (d, 2.26) , 6.80 (dd, 7.29, 2.29), 6.86 (d, 8.509), 7.01 (d, 7.93), 7.26 (dd, 7.85, 7.85), 7.37 (d, 8.53). Where m, s, and d represent the coupling states as multiplet, singlet, and doublet, respectively, and the numbers in parentheses indicate the coupling constants.

¹³ C-NMR (100 MHz) δ: 32.0 (t), 78.1 (d), 90.3 (s), 96.7 (d), 99.0 (d), 112.2 (d), 115.3 (d), 119.4 (d), 128.2 (d), 129.4 (d), 130.3 (s), 145.0 (s), 145.3 (s), 157.7 (s), 158.0 (s), 159.4 (s), 160.0 (s). Where s, d, and t represent the multiplicity of carbon and represent siglet, doublet, and triplet, respectively.

As can be seen in Figure 1, in the A-ring of the naringenin moiety in hydrogen nuclear magnetic resonance spectroscopy, there are two isolated peaks of 5.94 ppm and 6.01 ppm, and two hydrogens of 2.85 ppm and 3.30 ppm There was a peak and one hydrogen peak, 5.09 ppm. In addition, the hydroxyl group was substituted at the 4 'position in the B-ring, so that 6.86 ppm and 7.38 ppm corresponding to 2', 3 ', 5', and 4 'showed doublet coupling.

On the other hand, in carbon nuclear magnetic resonance spectroscopy, as shown in Figure 2, 17 peaks were observed, including two times the intensity, and one secondary carbon (methylene), eight tertiary carbon through DEPT experiment It consists of a method and eight quaternary carbons. Of these, the 115.3 ppm and 128.2 ppm carbon peaks present in the B-ring of the naringenin moiety are overlapping peaks that are twice as strong as those of other carbons, and 112.2 ppm and 129.4 ppm carbons present in phenylhydrazone. The peaks showed about twice the strength compared to 115.3 ppm hydrogen peak, confirming the overlapping peaks. HMQC experiment showed that hydrogen could be connected to each carbon, and 9.58ppm, 9.80ppm, and 12.56ppm peak of hydrogen-carbon unconnected were identified as hydrogen in hydroxyl group. The hydrogen peak is the peak connected with nitrogen, and the results are verified through the results of HMBC.

In addition, the COZY experiment showed that 5.09 ppm of tertiary hydrogen was 2.85 ppm and 3.30 ppm of secondary hydrogen, 6.86 ppm of tertiary hydrogen was 7.37 ppm of hydrogen, and 6.80 ppm of hydrogen peak was close to 7.26 ppm. It was confirmed that 7.26 ppm was close to 7.01 ppm hydrogen peak.

In addition, the HMBC experiment, which can confirm the linkage between the partial structure and the constituent elements, corresponds to 145.0 ppm hydrogen of the C-ring of the naringenin moiety and 112.2 ppm carbon present in the phenylhydrazone moiety. It was confirmed that the two parts are connected, the 9.58ppm hydrogen peak present in the hydroxyl group of the B-ring of naringenin is coupled with 115.3ppm hydrogen peak, and the 9.80ppm hydroxy hydrogen peak of the A-ring is 99.0ppm. Coupling with and 160.0ppm hydrogen was found to exist at position 5 of the A-ring. In addition, 12.56 ppm hydroxy hydrogen of the A-ring was coupled with long-range coupling with 96.7 ppm and 99.0 ppm carbon, and 99.0 ppm carbon showed simultaneous coupling with 9.80 ppm and 12.56 ppm hydrogen peaks, and 5.94 ppm The hydrogen peak showed long range coupling with 158.0 ppm and 159.4 ppm carbon peaks.

As described above, the long-distance coupling was confirmed through the HMBC experiment, the partial structure and the bonding state of Compound 1 were verified, and the connection of the adjacent hydrogen tips was confirmed through COZY, and the entire structure was confirmed by the previous experiments. .

In addition, in order to verify nuclear magnetic resonance spectroscopy experiments, a high-performance mass spectrometer was used to confirm the weight of 385.1164 (M + Na) ⁺ to which sodium was added, and it was verified that the material was composed of C ₂₁ H ₁₈ N ₂ O ₄ . This is the same as the result obtained by nuclear magnetic resonance spectroscopy.

Experimental Example 3. Confirmation of antioxidant effect

The antioxidant activity of the compound prepared in Example 1 was measured using DPPH (2,2-Diphenyl-1-picrylhydrazyl) to determine the relative antioxidant effect using vitamin C.

Specifically, 100 μl of the compound (1 mM) and 0.2 mM DPPH were added to 1 ml of the prepared Tris-HCl (100 mM, pH 7.4-7.5), and the mixture was stirred for 10 seconds and left for 20 seconds. Thereafter, the reaction was performed at about 37 ° C. for 15 minutes at 30 second intervals.

At this time, vitamin C was used as a standard for measuring the relative antioxidant capacity, and the color change of DPPH was measured by measuring the absorbance at 517 nm using an ultraviolet spectrophotometer (UV Spectrophotometer; Varian, Palo Alto, CA, USA). In addition, DPPH, methanol, Tris-HCl buffer (buffer) and the like were used as a control.

As a result, the compound of the present invention showed about 87.80% antioxidant activity compared to vitamin C.

As described above, specific portions of the contents of the present invention have been described in detail, and for those skilled in the art, these specific techniques are merely preferred embodiments, and the scope of the present invention is not limited thereto. Will be obvious. Accordingly, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

1 is a ¹ H-NMR spectrum graph of a novel cremendiol derivative according to the present invention.

Figure 2 is a ¹³ C-NMR spectrum of the novel cremendiol derivatives according to the present invention.

Claims (12)

The novel cremendiol derivative represented by the following formula (1) or a pharmaceutically acceptable salt thereof. [Formula 1]

The method of claim 1, The cremendiol derivative is a cremendiol derivative or a pharmaceutically acceptable salt thereof, characterized in that it has an active oxygen scavenging activity. The method of claim 1, The cremendiol derivative is a cremendiol derivative or a pharmaceutically acceptable salt thereof, characterized in that the DPPH (1,1-Diphenyl-2-picrylhydrazyl) scavenging activity. The method of claim 1, The cremendiol derivative is a cremendiol derivative or a pharmaceutically acceptable salt thereof, characterized in that used as an antioxidant. Claim 1 of the cremendiol derivative or a pharmaceutically acceptable salt thereof as an active ingredient, the brain disease, ischemia, heart disease, autoimmune disease, liver disease, arteriosclerosis, hyperlipidemia caused by excessive accumulation of active oxygen, A pharmaceutical composition for preventing and treating one or more diseases selected from diabetes mellitus, skin disease, rheumatism, inflammation, cancer or aging. The method of claim 5, The pharmaceutical composition is a brain disease, ischemia, heart disease, autoimmune disease, liver disease, arteriosclerosis, hyperlipidemia, diabetes, skin disease, rheumatism caused by excessive accumulation of active oxygen further comprising a pharmaceutically acceptable carrier, A pharmaceutical composition for preventing and treating one or more diseases selected from inflammation, cancer or aging. delete Anti-aging cosmetic composition comprising the cremendiol derivative of claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient. The method of claim 8, The cosmetic composition is a cosmetic composition, characterized in that the lotion, essence, lotion, cream, pack, gel, ointment, powder, patch or spray. Claim 1 of the cremendiol derivative or a pharmaceutically acceptable salt thereof as an active ingredient, the brain disease, ischemia, heart disease, autoimmune disease, liver disease, arteriosclerosis, hyperlipidemia caused by excessive accumulation of active oxygen, A dietary supplement for preventing and improving the symptoms of one or more diseases selected from diabetes mellitus, skin disease, rheumatism, inflammation, cancer or aging. A compound represented by the following Chemical Formula 1, which is prepared by using naringenin as a starting material, completely dissolving in ethanol, and then adding acetic acid and phenylhydrazine to heat and stirring at 80 to 120 ° C. for 3 to 20 hours. E) -2- (4-hydroxyphenly) -4- (2-phenylhydrazono) -3,4-dihydro-2H-chromene-5,7-diol. [Formula 1]

The method of claim 11, The naringenin and phenylhydrazine are added in a ratio of 1: 1 based on the molar ratio.

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