KR101845203B1 - Lauric acid derivatives, preparation method thereof and anticancer agent comprising the same - Google Patents

Abstract

The present invention relates to a lauric acid derivative, a manufacturing method thereof, and a composition for prevention, improvement and treatment of cancer including the same. A compound displayed by chemical formula 1 according to the present invention is excellent in anticancer activity, thereby being used for prevention, improvement and treatment of cancer. A pharmaceutical composition for prevention or treating cancer comprises the compound displayed by chemical formula 1 or a pharmaceutically acceptable salt thereof.

Description

Lauric acid derivatives, a method for preparing the same, and anticancer agents containing the same [

The present invention relates to a lauric acid derivative, a method for producing the same, and a composition for preventing, improving or treating cancer comprising the same.

Cancer cells differ in many ways from normal cells. Normal cells multiply by their needs and where they are needed. Normal cells appear to stick together. In addition, normal cells are destroyed by themselves when they are too old or damaged. However, cancer cells lack all of these functions and ultimately continue to divide to form tumors that are masses of cancer cells.

In Korea, the increase in the prevalence of chronic diseases and aging society has brought more attention not only to academia and industry but also to the general public. The treatment of cancer which is the first or second cause of death in the world is mostly therapeutic treatment using synthetic chemicals, causing hematopoiesis and immune function abnormality and toxicity to normal cells other than cancer cells. The development of anticancer drugs is required.

In general, MTT assay is a method to detect the growth of animal cells. Yellow tetrazolium salt MTT is a water-insoluble formazan crystal (3- (4,5-dimethylthiazol-2-yl) -2 , 5-diphenol-tetrazolium bromide), which is later dissolved in DMSO to measure the amount of crystal produced by absorbance. The greater the number of living cells, the greater the production of these crystals, so that the growth of cells can be measured easily.

The present inventors have devised a lauric acid derivative compound to synthesize a total of five kinds of lauric acid derivatives, and confirmed that the lauric acid derivative compound has an excellent cancer cell killing effect on breast cancer cells, and completed the present invention.

Korean Patent Publication No. 10-2016-0059084

An object of the present invention is to provide a pharmaceutical composition for preventing or treating cancer comprising the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof.

Another object of the present invention is to provide a health functional food and a health food composition for preventing or ameliorating cancer comprising the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof.

Another object of the present invention is to provide a process for producing the compound represented by the above formula (1).

In order to achieve the above object,

The present invention provides a pharmaceutical composition for preventing or treating cancer comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof.

[Chemical Formula 1]

In Formula 1,

,

,

,

및

로 이루어지는 군으로부터 선택되는 치환기이다.R ¹ is

,

,

,

And

≪ / RTI > is a substituent selected from the group consisting of

The present invention also provides a health functional food composition for preventing or ameliorating cancer comprising the compound represented by the above-mentioned formula (1) or a pharmaceutically acceptable salt thereof.

The present invention also provides a health food composition for preventing or ameliorating cancer, which comprises a compound represented by the above-mentioned formula (1) or a pharmaceutically acceptable salt thereof.

Further, the present invention relates to a process for preparing a compound represented by the following formula 1,

Dissolving lauric acid and resveratrol in an organic solvent, refluxing and stirring to obtain compound 1 (step 1);

Wherein R < 1 > and R < 2 >

[Reaction Scheme 1]

In the above Reaction Scheme 1,

또는

이다.Wherein R < ^{1 &}

or

to be.

Further, the present invention relates to a process for the preparation of

Dissolving lauric acid and Compound 2 in an organic solvent, refluxing and stirring to obtain Compound 1 (Step 1);

Wherein R < 1 > and R < 2 >

[Reaction Scheme 2]

In the above Reaction Scheme 2,

,

및

로 이루어지는 군으로부터 선택되는 치환기이다.Wherein R < ^{1 &}

,

And

≪ / RTI > is a substituent selected from the group consisting of

The compound represented by formula (I) according to the present invention is excellent in anticancer activity and thus may be useful for cancer prevention, improvement and treatment.

1 is a graph showing the survival rate (%) of cells according to the treatment concentration of the compound (LK1) of Example 1; (a) Breast cancer cells (MDA-MB231), (b) normal cells.

Hereinafter, the present invention will be described in detail.

Pharmaceutical composition for preventing or treating cancer

The present invention provides a pharmaceutical composition for preventing or treating cancer comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof.

In Formula 1,

,

,

,

및

로 이루어지는 군으로부터 선택되는 치환기이다.R ¹ is

,

,

,

And

≪ / RTI > is a substituent selected from the group consisting of

In the above pharmaceutical composition of the present invention, preferred examples of the compound represented by the formula (1) according to the present invention include the following compounds.

1) (E) -5- (4-hydroxystyryl) -1,3-phenyleneidenedodecanoate;

2) (E) -5- (4- (dodecanoyloxy) styryl) -1,3-phenyleneidenedodecanoate;

3) 4-acetamidophenyldodecanoate;

4) 2-acetoxybenzoyldodecanoic anhydride; And

5) Dodecanoic acid 2- (4-isobutylphenyl) propanoic anhydride.

The compound represented by the formula (1) of the present invention can be used in the form of a pharmaceutically acceptable salt, and as the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful. The term pharmaceutically acceptable salt means a concentration that is relatively non-toxic to a patient and has a beneficial effect that is harmless to the patient, such that the side effects caused by the salt are any organic or inorganic salt of the base compound of Formula 1 that does not impair the beneficial effects of the base compound of Formula An inorganic addition salt. Examples of the inorganic acid include hydrochloric acid, bromic acid, nitric acid, sulfuric acid, perchloric acid and phosphoric acid. Examples of the organic acid include citric acid, acetic acid, lactic acid, maleic acid, (D) or (L) malic acid, maleic acid, methanesulfonic acid, ethanesulfonic acid, maleic acid, tartaric acid, succinic acid, malonic acid, succinic acid, malonic acid, glutamic acid, aspartic acid, oxalic acid, P-toluenesulfonic acid, salicylic acid, citric acid, benzoic acid or malonic acid. These salts also include alkali metal salts (sodium salts, potassium salts, etc.) and alkaline earth metal salts (calcium salts, magnesium salts, etc.). For example, the acid addition salt may be selected from the group consisting of acetate, aspartate, benzoate, besylate, bicarbonate / carbonate, bisulfate / sulfate, borate, camylate, citrate, eddylate, Hydrobromide / bromide, hydroiodide / iodide, isethionate, lactate, malate, malate, glucoside, gluconate, gluconate, glucuronate, glucuronate, hexafluorophosphate, hibenzate, hydrochloride / Hydrogen phosphate, dihydrogen phosphate, dihydrogen phosphate, dihydrogen phosphate, dihydrogen phosphate, dihydrogen phosphate, dihydrogen phosphate, dihydroxyacetate, Lactate, stearate, succinate, tartrate, tosylate, trifluoroacetate Agent, may be included in the aluminum, arginine, benzathine, calcium, choline, diethylamine, diolamine, glycine, lysine, magnesium, meglumine, olamine, potassium, sodium, tromethamine and zinc salts.

The acid addition salt according to the present invention can be obtained by a conventional method, for example, by dissolving the compound represented by the formula (1) in an organic solvent such as methanol, ethanol, acetone, methylene chloride, acetonitrile and the like, Followed by filtration and drying. Alternatively, the solvent and excess acid may be distilled off under reduced pressure, followed by drying or crystallization in an organic solvent.

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

Furthermore, the present invention encompasses the compounds of formula (I) and pharmaceutically acceptable salts thereof as well as possible solvates, hydrates, isomers, optical isomers and the like which can be prepared therefrom.

In the pharmaceutical composition according to the present invention, the cancer may be breast cancer, colon cancer, pancreatic cancer, bone marrow cancer, and the like, preferably breast cancer.

The compound of the present invention may be administered orally or parenterally in various dosage forms during clinical administration. In the case of formulation, the diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, .

Solid form preparations for oral administration include tablets, patients, powders, granules, capsules, troches and the like, which may contain one or more excipients such as starch, calcium carbonate, It is prepared by mixing sucrose, lactose or gelatin. In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions or syrups. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like are included in addition to commonly used simple diluents such as water and liquid paraffin. .

Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. Examples of the non-aqueous solvent and suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As a base for suppositories, witepsol, macrogol, tween 61, cacao paper, laurin, glycerol, gelatin and the like can be used.

The effective dose of the compound of the present invention on the human body may vary depending on the patient's age, weight, sex, dosage form, health condition, and disease severity, and is generally about 0.001 to 100 mg / kg / 0.0 > mg / kg / day. ≪ / RTI > It is generally 0.07 to 7000 mg / day, preferably 0.7 to 2500 mg / day, based on an adult patient weighing 70 kg, and may be administered once a day, It may be divided into several doses.

Health functional food and health food composition for preventing or improving cancer

The present invention provides a health functional food or a health food composition for preventing or ameliorating cancer comprising a compound represented by the following general formula (1) or a pharmaceutically acceptable salt thereof.

[Chemical Formula 1]

In Formula 1,

,

,

,

및

로 이루어지는 군으로부터 선택되는 치환기이다.R ¹ is

,

,

,

And

≪ / RTI > is a substituent selected from the group consisting of

In the health functional food composition or the health food composition according to the present invention, the compound represented by the formula (1) may be any one selected from the following group of compounds.

1) (E) -5- (4-hydroxystyryl) -1,3-phenyleneidenedodecanoate;

2) (E) -5- (4- (dodecanoyloxy) styryl) -1,3-phenyleneidenedodecanoate;

3) 4-acetamidophenyldodecanoate;

4) 2-acetoxybenzoyldodecanoic anhydride; And

5) Dodecanoic acid 2- (4-isobutylphenyl) propanoic anhydride.

The health functional food composition or the health food composition according to the present invention may be formulated so as to prevent or ameliorate cancer by administering a compound represented by the general formula (1), a pharmaceutically acceptable salt thereof or an optical isomer thereof to a food, Functional food or health food.

In the pharmaceutical composition according to the present invention, the cancer may be breast cancer, colon cancer, pancreatic cancer, bone marrow cancer, and the like, preferably breast cancer.

There is no particular limitation on the kind of the food. Examples of the food to which the compound according to the present invention can be added include food products such as drinks, meat, sausage, bread, biscuits, rice cakes, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, Various soups, beverages, alcoholic beverages and vitamin complexes, dairy products and dairy products, and includes health foods and health functional foods in a conventional sense.

The health food and health functional food composition containing the compound according to the present invention can be added directly to food or can be used together with other food or food ingredients and can be suitably used according to conventional methods. The mixing amount of the compound according to the present invention can be appropriately determined depending on the purpose of use (for prevention or improvement). Generally, the amount of the compound in the health food and the health functional food may be 0.1 to 90 parts by weight of the total food. However, in the case of long-term intake for the purpose of health maintenance or health control, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.

The health food and health functional food composition of the present invention is not particularly limited to the other ingredients other than the compound containing the compound according to the present invention as an essential ingredient in the indicated ratios and may contain various flavors or natural carbohydrates, . Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 g of the health functional food composition of the present invention.

In addition to the above, the health food and the health functional food composition containing the compound according to the present invention can be used as a nutritional supplement, a vitamin, a mineral (electrolyte), a flavor such as a synthetic flavor and a natural flavor, ), Pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks and the like. In addition, the health food and health functional food composition of the present invention may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks.

These components may be used independently or in combination. The proportion of such additives is not so important, but is generally selected in the range of 0.1 to about 20 parts by weight per 100 parts by weight of the health food and health functional food composition containing the effective substance of the present invention.

Production methods 1 and 2

As shown in the following Reaction Scheme 1,

Dissolving lauric acid and resveratrol in an organic solvent, refluxing and stirring to obtain compound 1 (step 1);

Wherein R < 1 > and R < 2 >

[Reaction Scheme 1]

In the above Reaction Scheme 1,

또는

이다.Wherein R < ^{1 &}

or

to be.

Preferable examples of the compound represented by the general formula (1) prepared from the above Reaction Scheme 1 include the following compounds.

1) (E) -5- (4-hydroxystyryl) -1,3-phenyleneidenedodecanoate; And

2) (E) -5- (4- (Dodecanoyloxy) styryl) -1,3-phenylene dicidodecanoate.

In addition, the present invention relates to a process for producing a compound represented by the formula

Dissolving lauric acid and Compound 2 in an organic solvent, refluxing and stirring to obtain Compound 1 (Step 1);

Wherein R < 1 > and R < 2 >

[Reaction Scheme 2]

(In the above Reaction Scheme 2,

,

및

로 이루어지는 군으로부터 선택되는 치환기이다).Wherein R < ^{1 &}

,

And

≪ / RTI >

Preferable examples of the compound represented by the formula (1), which is prepared from the above reaction formula 2, include the following compounds.

3) 4-acetamidophenyldodecanoate;

4) 2-acetoxybenzoyldodecanoic anhydride; And

5) Dodecanoic acid 2- (4-isobutylphenyl) propanoic anhydride.

In the preparation method according to the present invention, the organic solvent is ethanol, tetrahydrofuran (THF), benzene, KOH / MeOH, MeOH, toluene, CH ₂ Cl _2, hexane, dimethylformamide (DMF), diisopropyl ether , Diethyl ether, dioxane, dimethylacetamide (DMA), dimethylsulfoxide (DMSO), acetone, chlorobenzene, etc. may be used alone or in combination. Preferably, tetrahydrofuran (THF) can be used as the organic solvent in the above step 1 of Scheme 1 and Scheme 2.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are illustrative of the present invention, and the present invention is not limited by the following examples.

Lauric acid  Preparation of derivatives

< Example  1-2> Preparation of lauric acid derivative 1

The method of synthesizing the lauric acid derivatives of Examples 1 and 2 is as shown in the following Reaction Scheme 1.

Specifically, lauric acid (6.06 g, 0.03 mol) and resveratrol (2.28 g, 0.01 mol) were added to a 250-mL one necked round-bottomed flask thoroughly dried at room temperature using a Deanstark apparatus in tetrahydrofuran tetrahydrofuran; THF) was refluxed with a solvent. After stirring for 24 hours, the water removed by deanstark was confirmed and the degree of reaction and completion were confirmed by TLC. The resulting solid reaction product was subjected to flash column chromatography to prepare the compounds of Examples 1 and 2 represented by the general formula (1).

[Reaction Scheme 1]

Example  1: (E) -5- (4- Hydroxystyryl ) -1,3- Phenylene Dydodecanoate  ((E) -5- (4-Hydroxystyryl) -1,3-phenylene didodecanoate)

The properties of the compound of Example 1 (1.60 g, yield of 27.0%) obtained through the above method are as follows.

Yield: 27.0%;

mp: 513-514 C;

_Rf : 0.4 (TLC eluent; EA: n-Hexane = 3: 7 v / v);

MASS (70 eV), m / z (rel. 592.4 (100), 593.4 (41.2), 591.4 (8.2);

¹ H NMR (CDCl ₃ , 400 MHz):? 0.87 (s, 6H), 1.25 (m, 32H), 1.61 (d, 4H), 2.55 1H) 6.91 (t, 4H);

¹³ C NMR (CDCl ₃ , 100 MHz): δ 178.997 (1C), 173.920 (1C), 156.390 (1C), 148.537 (2C), 138.889 (2C), 133.671 , 115.238 (4C), 33.963 (1C) 31.914 (1C), 29.607 (12C), 24.725 (1C), 22.695 (1C), 14.133 (2C);

Anal. calc. for C ₃₈ H ₅₆ O ₅ : C 76.99, H 9.52, O 13.49; Found: C 77.02, H 9.52, O 13.48.

Example  2: (E) -5- (4- ( Dodecanoyloxy ) Stiryl ) -1,3- Phenylene Daidodekanoe ((E) -5- (4- (Dodecanoyloxy) styryl) -1,3-phenylene didodecanoate )

The characteristics of the compound of Example 2 (3.02 g, yield 50.7%) obtained as a light brown liquid phase obtained through the above method are as follows.

Yield: 50.7%;

mp: sticky oil,

_Rf : 0.3 (TLC eluent; EA: n-Hexane = 3: 7 v / v);

MASS (70 eV), m / z (rel. 774.6 (100) 775.6 (54.1), 776.6 (14.3);

_{^{1 H NMR (CDCl 3, 400MHz}} ): δ 0.79 (t, 9H), 1.17 (s, 48H), 1.61 (m, 6H), 2.40 (m, 6H), 6.17 (s, 3H), 6.67 (s, 2H), 6.91 (s, 4H);

¹³ C NMR (CDCl ₃ , 100 MHz):? 180.363 (3C), 156.451 (1C), 156.400 (1C), 153.653 (1C), 133.457 (2C), 129.432 , 31.942 (1C), 29.637 (24C) 24.725 (1C), 22.718 (1C), 14.132 (3C);

Anal. calc. for C ₅₀ H ₇₈ O ₆ : C 77.47, H 10.14, O 12.38, Found: C 77.44, H 10.12, O 12.37.

< Example  3-5> Production of lauric acid derivative 2

The methods for synthesizing the lauric acid derivatives of Examples 3 to 5 are as shown in the following reaction formula (2).

Specifically, the lauric acid was added at a different concentration (2.00 g, 0.01 mol) to Compound 2 (Example 3: R ¹ = 4 -acetamido-phenyl -, 1.51g, 0.01mol; example 4: R ¹ = 2- acetoxy-benzoyl -, 1.80g, 0.01mol; example 5: R ¹ = 2- (4- isobutyl-phenyl) Pro Panoyl-, 2.06 g, 0.01 mol) were used to prepare the compounds of Example 3, Example 4 and Example 5 represented by the formula (1).

[Reaction Scheme 2]

Example 3: 4 - Acetamidophenyldodecanoate  (4-Acetamidophenyldodecanoate)

The characteristics of the compound of Example 3 (0.35 g, yield of 10.5%) as white solid obtained through the above method are as follows.

Yield: 10.5%;

mp: 289-290 占 폚;

_Rf : 0.3 (TLC eluent; EA: n-Hexane = 3: 7 v / v);

MASS (70 eV), m / z (rel. 332.2 (100), 334.2 (21.6), 335.2 (2.2);

_{^{1 H NMR (CDCl 3, 400MHz}} ): δ 0.81 (s, 3H), 1.12 (m, 24H), 1.69 (d, 2H), 2.05 (s, 3H), 2.47 (d, 2H), 6.92 (s, 2H), 7.38 (s, 2 H), 7.59 (s, 1 H);

¹³ C NMR (CDCl ₃ , 100 MHz): δ 172.770 (1C), 168.559 (1C), 146.797 (1C), 135.441 (1C), 121.899 (2C), 120.824 , 29.590 (6C), 24.913 (1C) 24.311 (1C), 22.677 (1C), 14.119 (1C);

Anal. calc. for C ₂₀ H ₃₁ NO ₃ : C 72.04, H 9.37, N 4.20, O 14.39; Found: C 72.02, H 9.35, N 4.21, O 14.38.

Example 4: 2 - Acetoxybenzoic acid Dodecanoi Anhydride  (2- Acetoxybenzoic  dodecanoic anhydride)

The characteristics of the compound of Example 4 (2.31 g, yield of 47.0%) as white solid obtained through the above method are as follows.

Yield: 47.0%;

mp: 218-219 캜;

R _f : 0.5 (TLC eluent; EA: n-Hexane = 5: 5 v / v);

MASS (70 eV), m / z (rel. 362.2 (100), 363.2 (22.7), 364.2 (2.5);

_{^{1 H NMR (CDCl 3, 400MHz}} ): δ 0.92 (t, 3H), 1.26 (m, 16H), 1.57 (t, 2H), 2.15 (s, 3H), 2.57 (t, 2H), 7.31 (d, 2H), 7.84 (d, 2H);

¹³ C NMR (CDCl ₃ , 100 MHz):? 175.521 (2C), 151.101 (1C), 150.897 (1C), 134.732 (1C), 132.553 (1C), 126.004 (1C), 124.136 (1C), 123.809 , 31.920 (1C), 34.141 (1C), 29.655 (14C), 24.491 (1C), 22.698 (1C), 14.139 (1C);

Anal. calc. for C ₂₀ H ₃₈ O ₃ : C 73.57, H 11.73, O 14.70; Found: C 73.58, H 11.72, O 14.72.

Example  5: Dodecanoi  2- (4- Isobutylphenyl ) Propanoi Anhydride  (Dodecanoic 2- (4- 이보 부록 ) propanoic  anhydride)

The properties of the compound of Example 3 (1.16 g, yield 29.9%) obtained by the above method are as follows.

Yield: 29.9%;

mp: 218-219 캜;

R _f : 0.8 (TLC eluent; EA: n-Hexane = 3: 7 v / v);

MASS (70 eV), m / z (rel. 388.3 (100), 389.3 (27.0), 390.3 (2.7);

^{1 H NMR (MeOD, 400MHz)} : δ 0.87 (t, 9H), 1.28 (s, 16H), 1.59 (dd, 6H), 2.26 (m, 2H), 2.42 (t, 2H), 4.08 (d, 1H ), 7.08 (d, 2H), 7.16 (d, 2H);

¹³ C NMR (MeOD, 100 MHz):? 175.145 (1C), 173.952 (1C), 137.977 (1C), 128.980 (1C), 126.815 (4C), 44.663 29.393 (1C), 25.845 (1C), 24.728 (1C), 21.415 (3C), 17.423 (1C), 13.164 (1C);

Anal. calc. _{for C 25 H 40 O 3:} C 77.27, H 10.38, O 12.35; Found: C 77.28, H 10.37, O 12.35.

< Experimental Example  1> Evaluation of apoptosis effect on breast cancer cell line

In order to evaluate the anticancer effect of the lauric acid derivative compound according to Example 1, the cytotoxic effect of the breast cancer cell line MDA-MB231 and the normal mammary cell MCF10A was analyzed as follows, and the results are shown in FIG.

Specifically, the breast cancer cell line MDA-MB231 and the normal mammary cell MCF10A were distributed from Korean Cell Line Bank (KCLB). Normal cells were cultured in DEME medium and breast cancer cells were cultured in RPMI medium. For cell culture, 10% FBS and 1% penicillin / streptomycin were added to each medium and incubated at 37 ° C and 5% CO ₂ incubator maintained at 95% humidity.

MTT assay was performed to measure apoptotic effect. 100 μL of each of the activated cell lines was added to 96-well plates at 2 × 10 ⁵ cells / mL, and the cells were pre-cultured for 24 hours at 37 ° C. and 5% CO 2 incubator. Cell culture medium (RPMI and DEME medium) 1 of lauric acid derivatives were treated at concentrations of 100, 200, 300, 400 and 500 μM, respectively. After incubation for additional 44 hours, 50 μL of MTT (2.5 mg / mL) dissolved in PBS buffer was added to each well and further incubated for 4 hours to induce formazan formation. After the reaction, the supernatant was removed and 200 μL of DMSO was added to dissolve the formazan formed on the well bottom. The absorbance was measured at 570 nm using an ELISA reader. The cell viability (%) was calculated according to the following equation (1).

[Equation 1]

Cell survival rate (%) = {1- (compound treated group absorbance / compound no treated group absorbance)} x 100

The cell viability (%) was measured by treating the lauric acid derivative compound of Example 1 at a concentration of 100, 200, 300, 400 and 500 μM on the breast cancer cells (MDA-MB231) and the normal cells (MCF10A) 1, the cancer cells were killed by the compound, and the survival rate of the cancer cells was decreased in a concentration-dependent manner. Normal cells showed nearly 100% survival rate and did not show a decrease in cell number (Fig. 1). Therefore, it was found that the lauric acid derivative compound according to Example 1 of the present invention specifically acts on cancer cells and has an anticancer effect of killing the cells.

These results suggest that the compounds according to the examples of the present invention have anticancer activity.

&Lt; Formulation Example 1 > Preparation of pharmaceutical preparation

<1-1> Preparation of powder

2 g &lt; RTI ID = 0.0 &gt;

Lactose 1 g

After mixing the above components, the mixture was packed in an airtight container to prepare a powder.

<1-2> Preparation of tablets

100 mg of the compound of formula (1)

Corn starch 100 mg

100 mg of milk

2 mg of magnesium stearate

After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.

&Lt; 1-3 > Preparation of capsules

100 mg of the compound of formula (1)

Corn starch 100 mg

100 mg of milk

2 mg of magnesium stearate

After mixing the above components, the capsules were filled in gelatin capsules according to the conventional preparation method of capsules.

<1-4> Preparation of Injection Solution

10 [mu] g / ml of the compound of formula (1)

Until dilute hydrochloric acid BP pH 3.5

Sodium chloride BP injected up to 1 ml

The compound of formula 1 according to the invention is dissolved in a suitable volume of sodium chloride BP and the pH of the resulting solution is adjusted to pH 3.5 with diluted hydrochloric acid BP and the volume is adjusted using injectable sodium chloride BP . The solution was filled in a 5 ml type I ampoule made of transparent glass, sealed in an upper lattice of air by dissolving the glass, sterilized by autoclaving at 120 DEG C for 15 minutes or longer, and an injection solution was prepared.

< Formulation example  2> Manufacture of health functional food and health food

<2-1> Production of Health Functional Food

100 mg of the compound of formula (1)

Vitamin mixture quantity

Vitamin A acetate 70 μg

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

0.15 mg of vitamin B2

Vitamin B6 0.5 mg

Vitamin B12 0.2 μg

Vitamin C 10 mg

Biotin 10 μg

Nicotinic acid amide 1.7 mg

Folic acid 50 μg

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a component suitable for a health functional food as a preferred embodiment, the compounding ratio may be arbitrarily changed, and the above components may be mixed , Granules may be prepared and used in the manufacture of health functional food compositions according to conventional methods.

<2-2> Preparation of Health Functional Drink

100 mg of the compound of formula (1)

Citric acid 100 mg

Oligosaccharide 100 mg

Plum concentrate 2 mg

Taurine 100 mg

Purified water was added to the whole 500 mL

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized container. The resulting solution was sealed and sterilized, &Lt; / RTI &gt; Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.

<2-3> Manufacture of dairy products

0.01-1 parts by weight of the lauric acid derivative compound of the formula (1) of the present invention was added to milk, and various dairy products such as butter and ice cream were prepared using the milk.

<2-4> Solar  Produce

Brown rice, barley, glutinous rice, and yulmu were dried by a known method and dried, and the mixture was granulated to a powder having a particle size of 60 mesh. Black soybeans, black sesame seeds, and perilla seeds were steamed and dried by a conventional method, and then they were prepared into powder having a particle size of 60 mesh by a pulverizer. The dry powders of cereals and seeds prepared above and the lauric acid derivative compounds of formula (I) of the present invention were prepared in the following proportions.

Grain (34 parts by weight of brown rice, 19 parts by weight of yulmu, 20 parts by weight of barley)

Seeds (7 parts by weight of perilla, 8 parts by weight of black beans, 7 parts by weight of black sesame seeds)

The compound of the formula (1) (2 parts by weight)

(1.5 parts by weight), and

Rhizome (1.5 parts by weight).

Claims (8)

A pharmaceutical composition for preventing or treating cancer comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof:
[Chemical Formula 1]

(In the formula 1,
R ¹ is

,

,

,

And

&Lt; / RTI &gt;
The method according to claim 1,
A pharmaceutical composition for preventing or treating cancer, wherein the compound represented by the formula (1) is any one selected from the group consisting of the following compounds:
1) (E) -5- (4-hydroxystyryl) -1,3-phenyleneidenedodecanoate;
2) (E) -5- (4- (dodecanoyloxy) styryl) -1,3-phenyleneidenedodecanoate;
3) 4-acetamidophenyldodecanoate;
4) 2-acetoxybenzoyldodecanoic anhydride; And
5) Dodecanoic acid 2- (4-isobutylphenyl) propanoic anhydride.
The method according to claim 1,
Wherein the cancer is breast cancer.
A health functional food composition for preventing or ameliorating cancer comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof:
[Chemical Formula 1]

(In the formula 1,
R ¹ is

,

,

,

And

&Lt; / RTI &gt;
A health food composition for preventing or ameliorating cancer comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof:
[Chemical Formula 1]

(In the formula 1,
R ¹ is

,

,

,

And

&Lt; / RTI &gt;
As shown in Scheme 1 below,
Dissolving lauric acid and resveratrol in an organic solvent, refluxing and stirring to obtain compound 1 (step 1);
(1), wherein R &lt; 1 &gt; and R &lt; 2 &gt;
[Reaction Scheme 1]

(In the above Reaction Scheme 1,
Wherein R &lt; ^{1 &}

or

to be).
delete delete

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