Novel spiroketal macrolide compound, method for producing same, and use thereof

Abstract

The present invention relates to a novel spiro-macrolide compound, a stereoisomer thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, a method for producing same, and a use thereof. As the compound has anticancer activity, the compound, a stereoisomer thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof may be used for preventing or treating cancer.

Description

Novel spiroketal macrolide compounds, methods for producing them, and uses thereof

[0001] The present invention relates to a novel spiroketal macrolide compound, a method for producing the same, and a use thereof.

[0002] Cancer, or malignant tumors, are a long-standing enemy of humanity, and despite the constant advancement of medicine, they are the most common cause of death in modern times. Cancer is a disease in which cells ignore the normal cycle of cell death and proliferate uncontrollably, disrupting bodily functions. Because cancer has diverse causes, symptoms, and pathogenesis vary greatly depending on the organ in which it develops, complete cure is extremely difficult. Furthermore, depending on the progression of the cancer, metastasis (the spread of cancer cells to other organs through bodily fluids like blood or lymph) can occur, making even treatment deemed successful the risk of recurrence undeniable. While mortality rates for diseases like rabies and Ebola hemorrhagic fever are higher than cancer, cancer is a terrifying disease because it is so common, yet it can be contracted at any time and in any place, and it is impossible to completely prevent it.

[0003] While a variety of anticancer drugs and treatments have been developed for cancer, effectively targeting all the various types of cancer cells that arise in various parts of the body remains a challenge. To this end, new types of anticancer drugs are constantly being developed, and their necessity for a complete cure is growing. Recently, research is underway to develop substances with anticancer activity from microorganisms.

[0004] Therefore, it is necessary to select microorganisms that produce useful physiologically active substances and to explore novel compounds with anticancer activity from them.

[0005]

[0006] Provided are novel spiroketal macrolide compounds, stereoisomers, solvates, or pharmaceutically acceptable salts thereof.

[0007] A strain of the genus Kitasatosporasp. producing the above compound or a stereoisomer thereof is provided.

[0008] A method for producing the above compound or a stereoisomer thereof is provided.

[0009] A pharmaceutical composition for preventing or treating cancer is provided, comprising the compound, a stereoisomer, a solvate, or a pharmaceutically acceptable salt thereof.

[0010] A method for preventing or treating cancer using the compound, a stereoisomer, a solvate, or a pharmaceutically acceptable salt thereof is provided.

[0011] The present invention provides use of the compound, a stereoisomer, a solvate, or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for preventing or treating cancer.

[0012]

[0013] One aspect provides a compound represented by chemical formula 1 or 2, a stereoisomer, a solvate, or a pharmaceutically acceptable salt thereof.

[0014] [Chemical Formula 1]

[0015]

[0016] [Chemical Formula 2]

[0017]

[0018] In the above chemical formulas 1 and 2, R1 may be -H or an acetyl group, R2 may be -H or -OH, and R3, R4, R5 and R6 may be -H or -CH3.

[0019]

[0020] In one specific example, the compound represented by the above chemical formula 1 may be a compound represented by the following chemical formula 3.

[0021] [Chemical Formula 3]

[0022]

[0023]

[0024] In another specific example, the compound represented by the above chemical formula 2 may be a compound represented by the following chemical formula 4.

[0025] [Chemical Formula 4]

[0026]

[0027]

[0028] Another aspect provides a strain of the genus Kitasatosporasp. producing a compound or a stereoisomer thereof according to one aspect.

[0029] The above Kitasatosporasp. strain belongs to Actinobacteria.

[0030] The strain may have a 16S rRNA gene having at least 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity with SEQ ID NO: 1. The strain may have the 16S rRNA gene of SEQ ID NO: 1.

[0031] The above strain includes its variants. The variants may be, for example, those resulting from natural mutations or artificial mutations. Artificial mutations may be caused by physical mutagens, such as ultraviolet light, or chemical mutagens, such as basic compounds.

[0032] The above strain includes spores, mycelia, or cultures of the strain.

[0033] The above strain may be isolated or derived from a termite nest.

[0034]

[0035] Another aspect provides a method for producing a compound according to one aspect or a stereoisomer thereof, comprising the steps of culturing Kitasatosporasp. INHA29 strain (Accession No.: KCTC15698BP); and isolating the compound according to one aspect or a stereoisomer thereof from a culture of the strain.

[0036] The above method comprises a step of culturing Kitasatosporasp. INHA29 strain (Accession No.: KCTC15698BP). The culturing step may be culturing the strain in a liquid medium or a solid medium. The medium may include, as a carbon source, for example, glucose, corn syrup, dextrin, starch, molasses, animal oil, or vegetable oil. The medium may include, as a nitrogen source, for example, wheat bran, soybean meal, wheat, malt, cottonseed meal, fish meal, corn syrup, meat juice, yeast extract, ammonium sulfate, sodium nitrate, or urea.

[0037] Cultivation can be performed under aerobic conditions with shaking or standing. The culture temperature can be, for example, about 20°C to about 40°C, about 25°C to about 37°C, about 28°C to about 35°C, or about 30°C. The culture time can be, for example, about 1 day to about 2 months, about 1 day to about 6 weeks, about 1 day to about 1 month, about 1 day to about 2 weeks, or about 1 day to about 1 week.

[0038] The method comprises a step of isolating a compound represented by any one of Chemical Formulas 1 to 4, more specifically a compound represented by Chemical Formula 3 or 4, or a stereoisomer thereof, from a culture of the strain.

[0039] The separation step may include concentrating, centrifuging, filtering, or performing chromatography on the culture medium. The chromatography may be, for example, column chromatography, planar chromatography, paper chromatography, or thin-layer chromatography, depending on the type of stationary phase. The chromatography may be, for example, gas chromatography, liquid chromatography, or affinity chromatography, depending on the physical properties of the mobile phase. The liquid chromatography may be, for example, high-performance liquid chromatography (HPLC). The chromatography may be, for example, ion exchange chromatography or size-exclusion chromatography, depending on the separation method. The chromatography may be, for example, normal phase chromatography or reverse phase chromatography.

[0040]

[0041] Another aspect provides a pharmaceutical composition for preventing or treating cancer comprising a compound according to one aspect, a stereoisomer, a solvate, or a pharmaceutically acceptable salt thereof.

[0042] The above cancers are not limited to a specific type. They can be solid or non-solid. Solid cancers refer to tumors that develop in organs such as the liver, lungs, breasts, and skin. Non-solid cancers originate in the blood and are also called hematologic cancers. The above cancers include, for example, intrahepatic cholangiocarcinoma, liver cancer, thyroid cancer, colon cancer, testicular cancer, myelodysplastic syndrome, glioblastoma, oral cancer, mycosis fungoides, acute myeloid leukemia, chronic myeloid leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, basal cell carcinoma, ovarian epithelial cancer, ovarian germ cell tumor, male breast cancer, brain tumor, pituitary adenoma, multiple myeloma, gallbladder cancer, biliary tract cancer, colon cancer, retinoblastoma, choroidal melanoma, ampulla of Vater cancer, bladder cancer, peritoneal cancer, parathyroid cancer, adrenal cancer, non-small cell lung cancer, tongue cancer, astrocytoma, small cell lung cancer, pediatric brain tumor, pediatric lymphoma, pediatric leukemia, small intestine cancer, meningioma, esophageal cancer, glioma, neuroblastoma, renal pelvic ureteral cancer, kidney cancer, malignant soft tissue tumor, malignant bone tumor, malignant lymphoma, malignant mesothelioma, It may be malignant melanoma, an ocular tumor, vulvar cancer, urethral cancer, cancer of unknown primary site, gastric lymphoma, gastric cancer, gastric carcinoid tumor, gastrointestinal stromal tumor, Wilms' tumor, breast cancer, sarcoma, penile cancer, pharyngeal cancer, gestational trophoblastic disease, cervical cancer, endometrial cancer, uterine sarcoma, prostate cancer, metastatic brain tumor, rectal cancer, rectal carcinoid tumor, vaginal cancer, spinal tumor, acoustic neuroma, pancreatic cancer, salivary gland cancer, tonsil cancer, squamous cell carcinoma, lung adenocarcinoma, lung cancer, lung squamous cell carcinoma, skin cancer, anal cancer, laryngeal cancer, or a combination thereof. The cancer may be, for example, at least one selected from the group consisting of gastric cancer, liver cancer, lung cancer, colon cancer, and breast cancer.

[0043] As used herein, the term "prevention" refers to any action that suppresses or delays the onset of a disease by administering a composition. As used herein, the term "treatment" refers to any action that improves or beneficially alters the symptoms of a disease by administering a composition.

[0044] The pharmaceutical composition may further comprise a known active ingredient having anticancer activity. The known active ingredient having anticancer activity may be an anticancer agent. The anticancer agent may be 5-fluorouracil, irinotecan, etoposide, oxaliplatin, leucovorin, capecitabine, or a combination thereof. The compound represented by the above chemical formula 1, a stereoisomer, a solvate, or a pharmaceutically acceptable salt thereof, and the anticancer agent may be a single or separate composition for simultaneous or sequential administration.

[0045] The pharmaceutical composition may further comprise a carrier, excipient or diluent. The carrier, excipient and diluent may include, for example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, or mineral oil.

[0046] The above pharmaceutical compositions may be formulated in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, or sterile injectable solutions, respectively, according to conventional methods. When formulating, the compositions may be prepared using diluents or excipients such as commonly used fillers, bulking agents, binders, wetting agents, disintegrants, and surfactants.

[0047] In the pharmaceutical composition, the solid preparation for oral administration may be a tablet, pill, powder, granule, or capsule. The solid preparation may further include an excipient. The excipient may be, for example, starch, calcium carbonate, sucrose, lactose, or gelatin. In addition, the solid preparation may further include a lubricant such as magnesium stearate or talc. In the pharmaceutical composition, the liquid preparation for oral administration may be a suspension, an oral solution, an emulsion, or a syrup. The liquid preparation may include water or liquid paraffin. The liquid preparation may include an excipient such as a wetting agent, a sweetener, a flavoring agent, or a preservative. In the above pharmaceutical composition, the preparation for parenteral administration may be a sterile aqueous solution, non-aqueous solvent, suspension, emulsion, lyophilized product, or suppository. The non-aqueous solvent or suspension may contain a vegetable oil or ester. The vegetable oil may be, for example, propylene glycol, polyethylene glycol, or olive oil. The ester may be, for example, ethyl oleate. The base of the suppository may be witepsol, macrogol, Tween 61, cocoa butter, laurin butter, or glycerogelatin.

[0048] The preferred dosage of the pharmaceutical composition above varies depending on the condition and body weight of the subject, the degree of the disease, the drug form, the route and period of administration, and can be appropriately selected by those skilled in the art. However, the compound, its isomer, derivative, solvate, or pharmaceutically acceptable salt may be administered in an amount of, for example, about 0.0001 mg / kg to about 100 mg / kg, or about 0.001 mg / kg to about 100 mg / kg, once to 24 times a day, once to 7 times every 2 days to 1 week, or once to 24 times every 1 month to 12 months. In the pharmaceutical composition, the compound, its isomer, derivative, solvate, or pharmaceutically acceptable salt may be included in an amount of about 0.0001 wt% to about 10 wt%, or about 0.001 wt% to about 1 wt%, based on the total weight of the entire composition.

[0049] Administration may be oral or parenteral. For example, the route of administration may be oral, transdermal, subcutaneous, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal, topical, intranasal, intratracheal, or intradermal. The composition may be administered systemically or locally, and may be administered alone or in combination with other pharmaceutically active compounds.

[0050]

[0051] Another aspect provides a health functional food for preventing or improving cancer, comprising a compound according to one aspect, a stereoisomer, a solvate, or a salt thereof.

[0052] As used herein, the term “improvement” includes any action that improves or benefits the symptoms of a disease.

[0053] The above health functional food can be used as a functional food or added to various foods by formulating a compound represented by any one of Chemical Formulas 1 to 4, more specifically, a compound represented by Chemical Formula 3 or 4, a stereoisomer, a solvate, or a salt thereof into an encapsulated, powdered, or suspension form. The above foods include, for example, meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, vitamin complexes, functional foods, and health foods.

[0054]

[0055] Another aspect provides a method of preventing or treating cancer, comprising administering to a subject a compound according to one aspect, a stereoisomer, a solvate, or a pharmaceutically acceptable salt thereof.

[0056] Another aspect provides the use of the compound, a stereoisomer, a solvate, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for preventing or treating cancer.

[0057] The subject may be a mammal, such as a human, cow, horse, pig, dog, sheep, goat, or cat. The subject may be diagnosed with cancer or may be at a high risk of being diagnosed with cancer.

[0058] The route of administration may be oral or parenteral. For example, the route of administration may be oral, transdermal, subcutaneous, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal, topical, intranasal, intratracheal, or intradermal. The pharmaceutical composition may be administered systemically or locally, and may be administered alone or in combination with other pharmaceutically active compounds.

[0059] The preferred dosage of the pharmaceutical composition may vary depending on the patient's condition and weight, the extent of the disease, the drug form, the route and duration of administration, and may be appropriately selected by those skilled in the art. For example, the dosage may be in the range of about 0.001 mg / kg to about 100 mg / kg, about 0.01 mg / kg to about 10 mg / kg, or about 0.1 mg / kg to about 1 mg / kg for adults. The administration may be administered once a day, multiple times a day, or once a week, once every two weeks, once every three weeks, or once every four weeks, or once a year.

[0060]

[0061] The novel spiroketal macrolide compound possesses anticancer activity and can therefore be used to prevent or treat various types of cancer. Furthermore, the newly isolated strain can be used to mass-produce the spiroketal macrolide compound at low cost and with high yield.

[0062]

[0063] Figure 1 is a photograph of a medium in which Kitasatosporasp. INHA29 strain was cultured.

[0064] Figure 2 shows the results of confirming the antitumor activity of a spiroketal macrolide compound according to the daily aspect.

[0065]

[0066] Hereinafter, preferred examples are presented to aid in understanding the present invention. However, the following examples are provided solely to facilitate a better understanding of the present invention, and the scope of the present invention is not limited by the following examples.

[0067]

[0068] Example 1. Isolation of Kitasatosporasp. INHA29 strain

[0069] Kitasatosporasp. INHA29 strain was isolated from a termite nest collected from Mt. Gwanak, Gwanak-gu, Seoul, Korea in 2019. Specifically, various isolation media were used for the strain isolation, and strain INHA29 was isolated after culturing on ISP4 agar medium at 28°C for 7 days. Subsequently, the strain was identified as a strain of Kitasatosporasp. based on the results of 16S rRNA sequence analysis. The strain was named Kitasatosporasp. INHA29 strain and deposited in the Korea Center for Microbial Resources (KCTC) (Accession Number: KCTC16598BP). The 16S rRNA gene sequence of strain INHA29 is represented by SEQ ID NO: 1.

[0070]

[0071] Example 2. Cultivation of INHA29 strain of the genus Kitasatospora

[0072] INHA29 strain of Kitasatospora genus was spread on YEME solid medium (10 g of malt extract, 4 g of yeast extract, 4 g of glucose, and 18 g of agar powder per L of distilled water) and cultured for primary cultivation at 30°C for approximately 4 weeks. Then, 50 mL of YEME liquid medium (10 g of malt extract, 4 g of yeast extract, and 4 g of glucose per L of distilled water) was prepared in a 125 mL flask, and the spores of INHA29 strain formed on the solid medium were inoculated, followed by secondary cultivation in an incubator at 30°C and 200 rpm for 3 days. Afterwards, the secondary liquid medium was inoculated into 10 mL of 200 mL YEME liquid medium in a 500 mL flask, and the tertiary cultivation was performed at 30°C and 170 rpm for 1 day. Afterwards, the 3rd liquid medium was inoculated into 25 mL of 1 L YEME liquid medium in a 2.5 L flask, and the 4th culture was performed at 30°C and 170 rpm for 5 days.

[0073]

[0074] Example 3. Extraction and isolation of spirosnuolide A and B from INHA29 strain culture broth.

[0075] Spirosunolides A and B were extracted and isolated from the INHA29 strain culture of Example 2. Specifically, a total of 45 L of the culture was extracted twice with 60 L of ethyl acetate (EtOAc) using a separatory funnel. First, the ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated in vacuo using a rotary evaporator to obtain 12 g of dried material. The crude extract was dissolved in methanol (MeOH), adsorbed with 5 gdp of Celite, loaded onto a C18 reversed-phase open column (34 X 150 mm), and sequentially fractionated with 500 mL aliquots of 20%, 40%, 60%, 80%, and 100% methanol to produce five fractions. A 15 μL aliquot of each fraction was analyzed by LC / MS. Spirosunolide A was detected in the 80% MeOH-H2O fraction, and spirosunolide B was detected in the 100% MeOH-H2O fraction. The 80% MeOH-H2O fraction was then evaporated and redissolved in MeOH, and chromatography was performed on a semi-preparative reversed-phase HPLC (Kromasil 100-5-C18, 250X10 mm, 5 mm) under gradient solvent conditions (60%–72% CH3CN-H2O containing 0.1% formic acid over 24 min; flow rate: 2 mL / min; UV detection: 210 nm). Spirosnulide A eluted at 19 min and was further purified using the same HPLC column under the same solvent conditions (58% CH3CN-H2O containing 0.1% formic acid; flow rate: 2 mL / min; UV detection: 210 nm) to obtain pure spirosnulide A at a retention time of 24 min. In addition, the 100% MeOH fraction was eluted at 19 min and further purified using the same gradient solvent conditions (0.Spirosnulide B was obtained by injecting it into the HPLC column and system using 65% to 85% CH3CN-H2O containing 1% formic acid for more than 30 minutes; flow rate: 2 mL / min; UV detection: 210 nm).

[0076]

[0077] Example 4. Physicochemical properties of spirosolides A and B

[0078] The structures of spiro-nurolides A and B were confirmed based on NMR spectra, and their physicochemical properties are as follows.

[0079] [spirosnuolide A]

[0080]

[0081] (1) Molecular formula: C 33 H 46 O 13

[0082] (2) Molecular weight: 650

[0083] (3) Color: White

[0084] (4) 1 H-NMR (CD3OD, 800 MHz): See Table 1

[0085] (5) 13 C-NMR (CD3OD, 200 MHz): See Table 1

[0086]

[0087] [Table 1]

[0088]

[0089]

[0090] [spirosunoilde B]

[0091]

[0092] (1) Molecular formula: C 33 H 44 O 11

[0093] (2) Molecular weight: 616

[0094] (3) Color: Yellow

[0095] (4) 1 H-NMR (CD3OD, 500 MHz): See Table 2

[0096] (5) 13 C-NMR (CD3OD, 125MHz): See Table 2

[0097]

[0098] [Table 2]

[0099]

[0100]

[0101] Experimental Example 1. Confirmation of the cytotoxicity of spiroglulic acid A and B against cancer cells.

[0102] The cytotoxicity of spironuolides A and B against various human cancer cells according to one specific example was evaluated. Specifically, the human lung cancer cell line A549, the colon cancer cell line HCT116, the gastric cancer cell line SNU68, the liver cancer cell line SK-HEP-1, and the breast cancer cell line DMA-MB-231, which were provided by the Korea Cell Line Bank (Seoul, Republic of Korea), were treated with spironuolide A or B obtained in the above example in FBS RPMI-1640 medium (A549, HCT116, and SNU638 cells) and DMEM medium (MDA-MB-231 and SK-HEP-1 cells) containing inactivated 10% fetal bovine serum (FBS) and antibiotic-antimycotic solution (penicillin G sodium 100 units / mL, streptomycin 100 μg / mL, and amphotericin B 250 ng / mL), respectively, for 72 hours. The cells were cultured for 1 h. Etoposide, an anticancer drug, was used as a positive control. Afterwards, the cells were stained with sulforhodamine (SRB), which stains only living cells, and the absorbance value at 515 nm was measured. The degree of growth inhibition against cancer cells was indirectly calculated using the absorbance value. The calculated IC 50 The values ​​(μM) are shown in Table 3 below.

[0103] [Table 3]

[0104]

[0105]

[0106] As a result, as shown in Table 3, it was confirmed that spironuolide B exhibited significant cytotoxicity against all cancer types.

[0107]

[0108] Experimental Example 2. Confirmation of the antitumor activity of spirostanolide B.

[0109] The antitumor activity of spironuolides A and B according to one specific example was confirmed in a cancer cell xenograft animal model. Specifically, HCC827 cell line (ATCC, Manassas, VA) was subcultured once or twice a week in RPMI-1640 medium (HyClone, Logan, UT) containing 10% heat-inactivated fetal bovine serum (FBS), 100 units / ㎖ of penicillin, 100 ㎍ / ㎖ of streptomycin, and 250 ng / ㎖ of amphotericin B at 37°C and 5% CO2 conditions. Thereafter, the cell line was cultured at a density of 1x10 6 / 200 μL cell concentration was injected subcutaneously into nude BALB / c mice (5-week-old, male) to prepare a cancer cell xenograft animal model. When the tumor size reached 100㎣, spironuolide B obtained in the above example was administered intraperitoneally to the xenograft animal model at concentrations of 0.5 mg / kg and 1 mg / kg, respectively, three times a week for 24 days. Gefitinib (MedChemExpress, NJ, USA) was used as a positive control. The tumor size and body weight of the xenograft animal model were measured at intervals of 3 to 5 days. The tumor size was calculated using a caliper according to the following mathematical equation 1.

[0110] [Mathematical Formula 1]

[0111]

[0112] Figure 2 shows the results of confirming the antitumor activity of a spiroketal macrolide compound according to the daily aspect.

[0113] As a result, as shown in Fig. 2, when 0.5 mg / kg and 1 mg / kg of spiroketal macrolide B were administered to the xenograft animal model, it was confirmed that the tumor size was reduced by 14.8% and 35.4%, respectively, compared to before administration. In addition, it was confirmed that the body weight of the xenograft animal model was maintained at a certain level regardless of the administered concentration of the spiroketal macrolide.

[0114] Therefore, spiroketal macrolides according to the daily pattern exhibit antitumor activity while minimizing side effects such as weight loss, and can be usefully used in the prevention or treatment of cancer.

[0115]

[0116] The foregoing description of the present invention is provided for illustrative purposes only. Those skilled in the art will readily appreciate that the present invention can be readily modified into other specific forms without altering the technical spirit or essential characteristics of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive.

[0117]

Claims

1. A compound represented by the following chemical formula 1 or 2, a stereoisomer, a solvate, or a pharmaceutically acceptable salt thereof; [Chemical Formula 1] [Chemical Formula 2] In the above chemical formulas 1 and 2, R1 is -H or an acetyl group, R2 is -H or -OH, R3, R4, R5 and R6 are -H or -CH3.

2. In claim 1, the chemical formula 1 is a compound represented by the following chemical formula 3, a stereoisomer, a solvate or a pharmaceutically acceptable salt thereof; [Chemical Formula 3] 3. In claim 1, the chemical formula 2 is a compound represented by the following chemical formula 4, a stereoisomer, a solvate or a pharmaceutically acceptable salt thereof; [Chemical Formula 4] 4. Kitasaphosphora genus (Kitasatosporasp.) INHA29 strain producing the compound of claim 1 or a stereoisomer thereof (Accession number: KCTC15698BP).

5. Step of culturing Kitasaphosphora genus (Kitasatosporasp.) INHA29 strain (Accession number: KCTC15698BP); and A method for producing a compound represented by chemical formula 1 or 2 or a stereoisomer thereof, comprising a step of isolating a compound represented by chemical formula 1 or 2 or a stereoisomer thereof from a culture of the strain.

6. A pharmaceutical composition for preventing or treating cancer, comprising a compound represented by the following chemical formula 1 or 2, a stereoisomer, a solvate, or a pharmaceutically acceptable salt thereof; [Chemical Formula 1] [Chemical Formula 2] In the above chemical formulas 1 and 2, R1 is -H or an acetyl group, R2 is -H or -OH, R3, R4, R5 and R6 are -H or -CH3.

7. A pharmaceutical composition for preventing or treating cancer, wherein the cancer according to claim 6 is at least one selected from the group consisting of stomach cancer, liver cancer, lung cancer, colon cancer, and breast cancer.

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