CN112500374B - Compound tenellone K, preparation method thereof and application thereof in preparing antitumor drugs - Google Patents
Compound tenellone K, preparation method thereof and application thereof in preparing antitumor drugs Download PDFInfo
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- CN112500374B CN112500374B CN202011410995.0A CN202011410995A CN112500374B CN 112500374 B CN112500374 B CN 112500374B CN 202011410995 A CN202011410995 A CN 202011410995A CN 112500374 B CN112500374 B CN 112500374B
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- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 229930191501 Tenellone Natural products 0.000 title claims description 17
- 238000000855 fermentation Methods 0.000 claims abstract description 13
- 230000004151 fermentation Effects 0.000 claims abstract description 13
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/18—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by etherified hydroxyl radicals
- C07D303/20—Ethers with hydroxy compounds containing no oxirane rings
- C07D303/24—Ethers with hydroxy compounds containing no oxirane rings with polyhydroxy compounds
- C07D303/26—Ethers with hydroxy compounds containing no oxirane rings with polyhydroxy compounds having one or more free hydroxyl radicals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D301/00—Preparation of oxiranes
- C07D301/32—Separation; Purification
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/02—Oxygen as only ring hetero atoms
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Abstract
The invention discloses a compound tenolone K, a preparation method thereof and application thereof in preparing antitumor drugs. The structural formula of the compound tenolone K is shown in a formula (I), and the compound tenolone K is obtained by separating and preparing from a fermentation culture of a marine fungus Phomopsis lithocarpus FS 508. Proved by tests, the compound tenolone K has IC on liver cancer cells HepG-2, breast cancer cells MCF-7, glioma cells SF-268 and non-small cell lung cancer cells A54950The value range is 11.36-51.62 mu M, the anti-tumor activity is relatively obvious, and the anti-tumor drug can be used for preparing anti-tumor drugs.
Description
Technical Field
The invention belongs to the technical field of medical biology, and particularly relates to a marine source compound tenolone K, a preparation method thereof and application thereof in preparing antitumor drugs.
Background
Since the discovery of thymidines (spongothymidines) and uridine (spongouridines) from the sponge Tectithya cryptata of the Caribbean in the 50 s of the last century, marine natural products have become new research hotspots for drug discovery. At present, marine microorganisms become important sources for exploring novel medicaments with novel structures, unique functions and remarkable activities, and have wide development prospects in aspects of innovative medicament exploration, novel enzyme preparation development, development of biological products with special functions, development of health-care products and the like. Phomopsis fungi are capable of producing structurally diverse novel secondary metabolites including various types of natural products such as terpenes, cytokinins, polyketides, steroids, lactones, and enols. Moreover, most of the natural products have wide biological activities such as anti-tumor, anti-inflammatory, antibacterial, antioxidant, antiviral and the like.
Disclosure of Invention
The first purpose of the invention is to provide a marine source compound, tenellone K, with antitumor activity.
The structure of the compound tenolone K is shown as the formula (I):
the second purpose of the invention is to provide a preparation method of a compound tenolone K, wherein the compound tenolone K is separated and prepared from a fermentation culture of a marine fungus Phomopsis lithocarpus FS508, and the preparation method specifically comprises the following steps:
(1) preparing a solid fermentation culture of a marine fungus Phomopsis lithocarpus FS508, extracting the solid fermentation culture by using ethyl acetate, and concentrating an ethyl acetate extract to obtain an extract;
(2) subjecting the extract to silica gel column chromatography, and performing gradient elution with petroleum ether/ethyl acetate at volume ratios of 10:1,5:1,2:1,1:1,0:1 and dichloromethane/methanol at volume ratios of 10:1,5:1 and 0:1 respectively as eluents; the petroleum ether/ethyl acetate fractions eluted at a volume ratio of 5:1 were collected and purified by TLC thin layer chromatography with n-hexane: developing ethyl acetate at a ratio of 1:2v/v to obtain a component Fr.6 with Rf of 0.3-0.4;
fr.6 separating by silica gel column chromatography with n-hexane/ethyl acetatePerforming gradient elution on the ester according to the volume ratio of 5:1,2:1,1:1,1:2, and collecting a component Fr.6-6 eluted by n-hexane/ethyl acetate according to the volume ratio of 2: 1; component Fr.6-6 is subjected to further C-18 reverse phase silica gel column chromatography with MeOH/H2Performing gradient elution on O according to the volume ratio of 70:30 → 100:0 to obtain 7 fractions Fr.6-6-1 to Fr.6-6-7; collect MeOH/H2The component Fr.6-6-3 and Fr.6-6-3 eluted by the volume ratio of 80:20 are separated by Sephadex LH-20 and are separated by CH2Cl2Eluting with MeOH at a volume ratio of 1:1, and combining the same components in the main spot by TLC spot plate to obtain 4 components Fr.6-6-3-1-Fr.6-6-3-4; and further carrying out silica gel column chromatographic separation on a component Fr.6-6-3-3 obtained by using a developing agent n-hexane/ethyl acetate according to the volume ratio of 2:1 and the Rf value of 0.5-0.6, eluting by using n-hexane/ethyl acetate according to the volume ratio of 5:1,2:1,1:1, collecting a component Fr.6-6-3-3-4 eluted by using the n-hexane/ethyl acetate according to the volume ratio of 2:1, and separating and purifying the component Fr.6-6-3-3-4 by using HPLC (high performance liquid chromatography) to obtain a compound tenellone K.
Further, the separation and purification of the component Fr.6-6-3-3-4 by HPLC specifically comprises the following steps: separating by full preparative HPLC on A YMC-pack ODS-A column with A mobile phase of methanol/water in A volume ratio of 80:20 and A flow rate of 6mL/min, collecting the eluted components with A retention time of 12min to obtain A component Fr.6-6-3-3-4-5, subjecting Fr.6-6-3-3-4-5 to further semi-preparative HPLC, using the YMC-pack ODS-A/AQ column with A mobile phase of acetonitrile/water in A volume ratio of 65:35 and A flow rate of 2mL/min, collecting the eluted components with A retention time of 26.2min to obtain the compound tenellone K.
The solid fermentation culture for preparing the marine fungus Phomopsis lithocarpus FS508 comprises the following specific steps: inoculating FS508 hyphae into a potato glucose liquid culture medium, culturing for 5 days at 28 ℃ and 120r/min to prepare a seed solution, then inoculating the seed solution into a rice culture medium according to the inoculation amount of 0.1mL/g, and culturing for 30 days at 28 ℃ to prepare a solid fermentation culture of FS508, wherein each liter of the potato glucose liquid culture medium is prepared by the following method: boiling 200g of potato in 500mL of pure water for 20min, filtering to obtain potato juice, and adding glucose 20g and KH2PO4 3g、MgSO41.5g, vitamin B110mg of waterSupplementing to 1000mL, and sterilizing to obtain the final product; the rice culture medium is prepared by the following method: mixing 250g rice with 300mL of crude sea salt water solution with mass volume ratio of 0.5% g/mL, and sterilizing.
The third purpose of the invention is to provide the application of the compound tenolone K or the medicinal salt thereof in preparing the antitumor drugs. The anti-tumor drug is preferably a drug for resisting liver cancer, breast cancer, glioma or non-small cell lung cancer.
Experiments show that the compound tenolone K has IC (integrated Circuit) on liver cancer cells HepG-2, breast cancer cells MCF-7, glioma cells SF-268 and non-small cell lung cancer cells A54950The value range is 11.36 to 51.62 μ M. IC of positive control cisplatin on four tumor cell lines50The values were 2.13, 3.02, 3.25 and 2.65. mu.M, respectively. This result shows that: the compound tenellone K has relatively obvious antitumor activity.
The fourth purpose of the invention is to provide an antitumor drug, which contains the compound tenolone K or the medicinal salt thereof as an active ingredient, preferably, the antitumor drug is a drug for resisting liver cancer, breast cancer, glioma or non-small cell lung cancer.
The fifth object of the present invention is to provide the use of the marine fungus Phomopsis lithocarpus FS508 for the preparation of the above-mentioned compound tenolone K.
Compared with the prior art, the invention has the advantages that:
the compound tenolone K is separated and prepared from marine fungus Phomopsis lithocarpus FS508, has relatively obvious antitumor activity, can be used for preparing antitumor drugs, provides candidate compounds for researching and developing new antitumor drugs, and provides scientific basis for developing and utilizing natural active substances from marine microorganisms.
The marine fungus Phomopsis lithocarpus FS508 of the present invention was deposited at the Guangdong province culture Collection (GDMCC) at 8.8.15.2018, with the address: no. 59 building 5 of No. 100 Dazhong Ji of Pieli, Guangzhou city, its preservation number is GDMCC No. 60433.
Drawings
FIG. 1 is an HR-ESIMS spectrum of compound tenolone K;
FIG. 2 is a drawing of the compound tenolone K1H NMR spectrum;
FIG. 3 is a drawing of the compound tenolone K13C NMR spectrum;
FIG. 4 is a drawing of the compound tenolone K1H-1H COSY spectrum;
FIG. 5 is the HSQC spectrum of compound tenolone K;
FIG. 6 is an HMBC spectrum of compound tenolone K;
FIG. 7 is a UV spectrum of compound tenolone K;
FIG. 8 is a CD spectrum of compound tenolone K;
FIG. 9 is an IR spectrum of compound tenolone K.
Detailed Description
The following examples are further illustrative of the present invention and are not intended to be limiting thereof.
Example 1
1. Isolation, purification and characterization of the marine fungus Phomopsis lithocarpus FS508
The marine fungus Phomopsis lithocarpus FS508 of the invention is separated from deep sea sediments of Indian ocean (16 degrees 50.508'N,111 degrees 53.335' E, water depth 3606 meters) in 2016 (5 months) in 2016, and is identified by ITS sequence analysis, and GenBank gene accession numbers are: MG686131, identified by blast alignment and homology analysis as belonging to the genus Phomopsis, named Phomopsis lithocarpus FS508, deposited at the guangddong collection of microbial cultures (GDMCC) at 8, 15 months in 2018, address: no. 59 building 5 of No. 100 Dazhong Ji of Pieli, Guangzhou city, its preservation number is GDMCC No. 60433.
2. Solid fermentation of Phomopsis lithocarpus FS508
Inoculating activated mycelium of Phomopsis lithocarpus FS508 to potato glucose liquid culture medium (per liter culture medium is prepared by decocting 200g of potato in 500mL of pure water, boiling for 20min, filtering to obtain potato juice, adding glucose 20g and KH2PO4 3g、MgSO41.5g, vitamin B110mg, made by supplementing to 1000mL with water and sterilizing), cultured at 28 ℃ for 5 days at 120r/min to prepare a seed solution, and then inoculated into a rice medium in an inoculum size of 0.1mL/g (prepared by the following method: mixing 250g rice with 300mL of crude sea salt water solution with mass volume ratio of 0.5% mg/mL, autoclaving at 121 deg.C for 20min, and cooling) and culturing at 28 deg.C for 30 days to obtain FS508 solid fermentation culture.
3. Preparation of compound tenellone K
(1) Adding ethyl acetate into FS508 solid fermentation culture, soaking and extracting for 24 hours, repeatedly extracting for 3 times, mixing the extracting solutions, and concentrating to obtain extract (177.9 g).
(2) Subjecting the extract obtained in the step (1) to silica gel column chromatography, and performing gradient elution by using petroleum ether/ethyl acetate as an eluent in a volume ratio of 10:1,5:1,2:1,1:1,0:1 and dichloromethane/methanol in a volume ratio of 10:1,5:1,0:1 respectively; the petroleum ether/ethyl acetate fractions eluted at a volume ratio of 5:1 were collected and purified by TLC thin layer chromatography with n-hexane: developing ethyl acetate at a ratio of 1:2v/v to obtain a component Fr.6 with Rf of 0.3-0.4;
fr.6 separating by silica gel column chromatography, gradient eluting with n-hexane/ethyl acetate at volume ratio of 5:1,2:1,1:1,1:2, collecting component Fr.6-6 eluted with n-hexane/ethyl acetate at volume ratio of 2: 1; component Fr.6-6 is subjected to further C-18 reverse phase silica gel column chromatography with MeOH/H2Performing gradient elution on O according to the volume ratio of 70:30 → 100:0 to obtain 7 fractions Fr.6-6-1 to Fr.6-6-7; collect MeOH/H2The component Fr.6-6-3 and Fr.6-6-3 eluted by the volume ratio of 80:20 are separated by Sephadex LH-20 and are separated by CH2Cl2Eluting with MeOH at a volume ratio of 1:1, and combining the same components in the main spot by TLC spot plate to obtain 4 components Fr.6-6-3-1-Fr.6-6-3-4; fr.6-6-3-3-3 (a developing agent is n-hexane/ethyl acetate of 2:1v/v, and the Rf value is 0.5-0.6) is further subjected to silica gel column chromatography separation, n-hexane/ethyl acetate is used for elution according to the volume ratio of 5:1,2:1,1:1, and a component Fr.6-6-3-3-4 eluted according to the volume ratio of 2:1 of n-hexane/ethyl acetate is collected;
separating the component Fr.6-6-3-3-4 by full preparative HPLC on A YMC-pack ODS-A column with A mobile phase of methanol/water in A volume ratio of 80:20 and A flow rate of 6mL/min, collecting the eluted component with A retention time of 12min to obtain A component Fr.6-6-3-3-4-5, subjecting Fr.6-6-3-3-4-5 to further semi-preparative HPLC using A YMC-pack ODS-A/AQ column with A mobile phase of acetonitrile/water in A volume ratio of 65:35 and A flow rate of 2mL/min, collecting the eluted component with A retention time of 26.2min to obtain A compound tenellone K (1.1 mg).
4. Structural identification of compound tenolone K
1H-NMR、13C-NMR and HMBC nuclear magnetic resonance spectrograms are measured by a Bruker advanced-600 nuclear magnetic resonance spectrometer, and Tetramethylsilane (TMS) is taken as an internal standard; ESI-MS data were measured with VG Autospec-3000 type mass spectrometer; the ultraviolet spectrum is measured by an Shimadzu UV-2600 spectrophotometer, and the structure identification is as follows:
as shown in FIGS. 1-9, FIG. 1 is an HR-ESIMS spectrum of the compound tenolone K; FIG. 2 is a drawing of the compound tenolone K1H NMR spectrum; FIG. 3 is a drawing of the compound tenolone K13C NMR spectrum; FIG. 4 is a drawing of the compound tenolone K1H-1H COSY spectrum; FIG. 5 is the HSQC spectrum of compound tenolone K; FIG. 6 is an HMBC spectrum of compound tenolone K; FIG. 7 is a UV spectrum of compound tenolone K; FIG. 8 is a CD spectrum of compound tenolone K; FIG. 9 is an IR spectrum of compound tenolone K.
The compound tenellone K was a yellow oil (nuclear magnetic data are shown in table 1); according to HRESIMS [ M + Na ]]+m/z 465.1884，C25H30NaO7Calculated value of 465.1877, the molecular formula of the compound was determined to be C25H30O7Unsaturation is 11;1H-NMR spectrum showed four olefinic proton signals [6.88(d, J ═ 8.3Hz, H-4),7.11(d, J ═ 8.3Hz, H-5),5.05(t, J ═ 97.3Hz, H-18),7.04(s, H-4')](ii) a5 methyl hydrogen signals [ delta ]H 1.64(s,H3-10),1.60(s,H3-11),2.12(s,H3-7'),1.31(s,H3-11'),1.27(s H3-12′)]。13The C-NMR spectrum and the HSQC spectrum showed 25 carbon signals in Compound 1, including 13 quaternary carbons (including 1 carbonyl carbon), 4 methines, 3 methylenes, and 5 methyl groups. Above knotThe compound tenellone K is shown to be a typical tenellone derivative. The structure of the compound tenolone K is determined by further analyzing two-dimensional spectrograms of COSY, HSQC, HMBC and the like.
TABLE 1 Nuclear magnetic data of the compound tenolone K (600MHz/150MHz, delta in ppm, J in Hz)
*Not detected；**Detected by HMBC
The structural formula of the target compound tenolone K separated by the method is shown as the formula (I):
example 2
The anti-tumor activity of compound tenolone K was tested using the SRB method (Skehan P, stopping R, Dominic S.New colorimetric cytoxicity assay for anti-cancer-drug screening [ J ]. J Natl cancer Inst,1990,82: 1107-1112.).
1. Test reagents: the compound tenellone K prepared by the invention is dissolved by dimethyl sulfoxide (DMSO) to obtain a mother solution with the concentration of 10mg/mL, and then the mother solution is diluted to the required concentration by RPMI-1640 culture medium. The positive control is cisplatin aqueous solution.
The tumor cell strains used in the experiment are liver cancer cell HepG-2, breast cancer cell MCF-7, glioma cell SF-268 and non-small cell lung cancer cell A549.
2. The experimental method comprises the following steps: taking HepG-2, MCF-7, SF-268 and A549 cells in logarithmic growth phase, digesting with pancreatin, staining and counting with trypan blue, adjusting the cell concentration to 3 x 10 by using fresh RPMI-1640 culture medium after detecting that the cell activity is more than 95% by using trypan blue exclusion experiment4cell/mL, cell inoculation in96-well plate, adding 180 μ L cell suspension per well, setting 3 blank wells for zero setting, and adjusting temperature at 37 deg.C and 5% CO2The incubator is used for 24 h. After the cells are attached to the wall, 20 mu L of a solution of the compound tenolone K with a certain concentration is added into each hole, 20 mu L of RPMI-1640 culture medium is added into the negative control, and cisplatin is used as the positive control. Placing at 37 ℃ and 5% CO2Culturing in incubator for 72h, adding 50 μ L cold trichloroacetic acid aqueous solution with volume fraction of 50% to fix cells, standing at 4 deg.C for 1h, washing with distilled water for 5 times, and air drying. Sulforhodamine B (SRB) 4mg/mL solution prepared from 1% glacial acetic acid solution by volume fraction was added to 100. mu.L/well, stained at room temperature for 30min, the supernatant was removed, washed 5 times with 1% v/v glacial acetic acid solution, and air-dried. Finally adding 200 mu L/hole of Tris solution with the concentration of 10mmol/mL, measuring the absorbance (A) at 570nm by using a microplate reader, and calculating the inhibition rate of the drug on the cell growth by using the following formula: cell growth inhibition (%) - (1-A)Sample set/AControl group)×100％。
3. The experimental results are as follows: the cytotoxicity of the compound tenolone K prepared by the invention on four tumor cells is shown in Table 2. This result shows that: the compound tenellone K has relatively obvious antitumor activity, so that the compound tenellone K provides candidate compounds for researching and developing new antitumor drugs, and provides scientific basis for developing and utilizing natural active substances derived from deep-sea microorganisms.
TABLE 2 inhibitory Effect of the Compound tenolone K on cancer cells
The above is only a preferred embodiment of the present invention, and it should be noted that the above preferred embodiment should not be considered as limiting the present invention, and the protection scope of the present invention should be subject to the scope defined by the claims. It will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the spirit and scope of the invention, and these modifications and adaptations should be considered within the scope of the invention.
Claims (6)
1. A compound, tenellone K, represented by the formula (І):
formula (І).
2. A process for the preparation of the compound tenolone K of claim 1 wherein said compound tenolone K is obtained from marine fungiPhomopsis lithocarpusSeparating and preparing the fermentation culture of FS 508; the method specifically comprises the following steps:
(1) preparation of marine fungiPhomopsis lithocarpusExtracting the solid fermentation culture of FS508 by using ethyl acetate, and concentrating an ethyl acetate extract to obtain an extract;
(2) subjecting the extract to silica gel column chromatography, and performing gradient elution with petroleum ether/ethyl acetate at volume ratios of 10:1,5:1,2:1,1:1,0:1 and dichloromethane/methanol at volume ratios of 10:1,5:1 and 0:1 respectively as eluents; the petroleum ether/ethyl acetate fractions eluted at a volume ratio of 5:1 were collected and purified by TLC thin layer chromatography with n-hexane: ethyl acetate =1: 2v/v developing a component fr.6 with Rf = 0.3-0.4;
fr.6 separating by silica gel column chromatography, gradient eluting with n-hexane/ethyl acetate at volume ratio of 5:1,2:1,1:1,1:2, collecting component Fr.6-6 eluted with n-hexane/ethyl acetate at volume ratio of 2: 1; component Fr.6-6 is subjected to further C-18 reverse phase silica gel column chromatography with MeOH/H2Performing gradient elution on O according to the volume ratio of 70:30 → 100:0 to obtain 7 fractions Fr.6-6-1 to Fr.6-6-7; collect MeOH/H2The component Fr.6-6-3 and Fr.6-6-3 eluted by the volume ratio of 80:20 are separated by Sephadex LH-20 and are separated by CH2Cl2The MeOH eluted at a volume ratio of 1:1 was combined by TLC spot platesThe same components are spotted to obtain 4 components Fr.6-6-3-1 to Fr.6-6-3-4; further separating a component Fr.6-6-3-3 with a developing agent of n-hexane/ethyl acetate according to a volume ratio of 2:1 and an Rf value of 0.5-0.6 by silica gel column chromatography, eluting with n-hexane/ethyl acetate according to a volume ratio of 5:1,2:1,1:1, collecting a component Fr.6-6-3-4 eluted by the n-hexane/ethyl acetate according to a volume ratio of 2:1, and separating and purifying the component Fr.6-6-3-3-4 by HPLC to obtain a compound tenellone K;
the separation and purification of the component Fr.6-6-3-3-4 by HPLC specifically comprises the following steps: separating by full preparative HPLC on A YMC-pack ODS-A column with A mobile phase of methanol/water in A volume ratio of 80:20 and A flow rate of 6mL/min, collecting the eluted components with A retention time of 12min to obtain A component Fr.6-6-3-3-4-5, subjecting Fr.6-6-3-3-4-5 to further semi-preparative HPLC, using the YMC-pack ODS-A/AQ column with A mobile phase of acetonitrile/water in A volume ratio of 65:35 and A flow rate of 2mL/min, collecting the eluted components with A retention time of 26.2min to obtain the compound tenellone K.
3. The method according to claim 2, wherein the step (1) of preparing marine fungiPhomopsis lithocarpusThe solid fermentation culture of FS508 comprises the following specific steps: inoculating FS508 hyphae into a potato glucose liquid culture medium, culturing for 5 days at 28 ℃ and 120r/min to prepare a seed solution, then inoculating the seed solution into a rice culture medium according to the inoculation amount of 0.1mL/g, and culturing for 30 days at 28 ℃ to prepare a solid fermentation culture of FS508, wherein each liter of the potato glucose liquid culture medium is prepared by the following method: boiling 200g of potato in 500mL of pure water for 20min, filtering to obtain potato juice, and adding glucose 20g and KH2PO4 3 g、MgSO41.5g, vitamin B110mg, supplementing water to 1000mL, and sterilizing; the rice culture medium is prepared by the following method: mixing 250g rice with 300mL of crude sea salt water solution with mass volume ratio of 0.5% g/mL, and sterilizing.
4. The use of the compound tenolone K or pharmaceutically acceptable salt thereof of claim 1 for the preparation of an antitumor medicament; the anti-tumor drug is a drug for resisting liver cancer, breast cancer, glioma or non-small cell lung cancer.
5. An antitumor agent characterized by comprising the compound tenolone K according to claim 1, or a pharmaceutically acceptable salt thereof as an active ingredient.
6. Marine fungiPhomopsis lithocarpusUse of FS508 for the preparation of the compound tenolone K according to claim 1.
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