CN106389417A - Application of penem alcohol E1 derived from trichoderma citrinoviride in aspect of gastric cancer - Google Patents
Application of penem alcohol E1 derived from trichoderma citrinoviride in aspect of gastric cancer Download PDFInfo
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- CN106389417A CN106389417A CN201610819719.7A CN201610819719A CN106389417A CN 106389417 A CN106389417 A CN 106389417A CN 201610819719 A CN201610819719 A CN 201610819719A CN 106389417 A CN106389417 A CN 106389417A
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- Prior art keywords
- gastric cancer
- alcohol
- penem
- compound
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- 208000005718 Stomach Neoplasms Diseases 0.000 title claims abstract description 21
- 206010017758 gastric cancer Diseases 0.000 title claims abstract description 19
- 201000011549 stomach cancer Diseases 0.000 title claims abstract description 17
- 241000596490 Trichoderma citrinoviride Species 0.000 title abstract description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title abstract description 4
- HHXMXAQDOUCLDN-RXMQYKEDSA-N penem Chemical compound S1C=CN2C(=O)C[C@H]21 HHXMXAQDOUCLDN-RXMQYKEDSA-N 0.000 title abstract description 4
- 239000003814 drug Substances 0.000 claims abstract description 12
- 241000675108 Citrus tangerina Species 0.000 claims description 11
- 241000223259 Trichoderma Species 0.000 claims description 11
- 150000002085 enols Chemical class 0.000 claims description 10
- 230000035755 proliferation Effects 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 abstract description 20
- 230000000694 effects Effects 0.000 abstract description 9
- 230000000259 anti-tumor effect Effects 0.000 abstract description 5
- 230000005764 inhibitory process Effects 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract description 2
- 238000002474 experimental method Methods 0.000 abstract description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract description 2
- 230000009702 cancer cell proliferation Effects 0.000 abstract 1
- 239000003560 cancer drug Substances 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
- 235000021003 saturated fats Nutrition 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000284 extract Substances 0.000 description 8
- 229930013930 alkaloid Natural products 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 201000000498 stomach carcinoma Diseases 0.000 description 6
- 150000003797 alkaloid derivatives Chemical class 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- XILIYVSXLSWUAI-UHFFFAOYSA-N 2-(diethylamino)ethyl n'-phenylcarbamimidothioate;dihydrobromide Chemical compound Br.Br.CCN(CC)CCSC(N)=NC1=CC=CC=C1 XILIYVSXLSWUAI-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 208000010749 gastric carcinoma Diseases 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- -1 Alkaloid compound Chemical class 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000013096 assay test Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000012490 blank solution Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005100 correlation spectroscopy Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000003950 cyclic amides Chemical class 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 1
- 238000001052 heteronuclear multiple bond coherence spectrum Methods 0.000 description 1
- 238000003929 heteronuclear multiple quantum coherence Methods 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000006101 laboratory sample Substances 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- LPUQAYUQRXPFSQ-DFWYDOINSA-M monosodium L-glutamate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCC(O)=O LPUQAYUQRXPFSQ-DFWYDOINSA-M 0.000 description 1
- 235000013923 monosodium glutamate Nutrition 0.000 description 1
- 239000004223 monosodium glutamate Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 238000004262 preparative liquid chromatography Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002525 ultrasonication Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/36—Oxygen or sulfur atoms
- C07D207/38—2-Pyrrolones
-
- C—CHEMISTRY; METALLURGY
- 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
- C12P17/10—Nitrogen as only ring hetero atom
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention relates to application of penem alcohol E1 derived from trichoderma citrinoviride in the aspect of gastric cancer. The compound is structurally characterized in that a molecular skeleton of pentacycloamide is contained, a carbonyl is contained and connected with a decacarbon saturated fat long chain, a methyl is connected on N, and two hydroxyl groups exist in a molecule. Experiments verify that the alkaloid-type compound has high inhibition activity to gastric cancer cells. The penem alcohol E1 can be used for preparing gastric cancer cell proliferation inhibition drugs or anti-gastric-cancer drugs and can be used for antitumor study.
Description
Technical field
The present invention relates to a kind of come from the mould enol E1 of tangerine green trichoderma and its application in terms of cancer of the stomach.
Background technology
Alkaloid is the organic compounds containing nitrogen that a class is produced by biological cometabolism, and the alkaloid species in nature is relatively
Many, mostly derive from plant, therefore have the title of vegetable soda again.Alkaloid has important physiological action to humans and animals, including flat
Breathe heavily antibechic, hypoglycemic, reducing blood lipid, antibacterial, antitumor, analgesia etc., wherein prominent with antibacterial, antitumor activity.Natural knot
Structure alkaloid is the important sources finding lead compound in innovation drug research, has been applied to the alkaloidal drug of clinic at present
Through nearly hundred kinds.Research finds, some marine fungis can produce the biology that structure is novel, activity is good during cometabolism
Alkali, has medicinal well and industrialization prospect.
The present inventor's research is learnt, tangerine green trichoderma（Trichoderma citrinoviride.）IBPT-4 is (in 2013
On January 25, in is deposited in China typical culture collection center, address:Wuhan Wuhan University, deposit number is：CCTCC
NO：M 2013055) the CE of tunning have good tumor cell proliferation inhibition activity, then to its active component
Studied, this tangerine green trichoderma（Trichoderma citrinoviride.）IBPT-4 is in the patent No. 201310208563.5
Disclosed.Alkaloid compound shown in research discovery has antitumor activity for cancer of the stomach, has not yet to see this compound
Chemical constitution and the report for proliferation of human gastric cancer cell inhibitory activity, also there is not yet medicine related to this therefore on market.
Content of the invention
It is an object of the invention to provide a kind of come from the mould enol E1 of tangerine green trichoderma and its application in terms of cancer of the stomach.
Present invention firstly relates to one plant of tangerine green trichoderma（Trichoderma citrinoviride.）IBPT-4, this bacterial strain
It is deposited in China typical culture collection center, address on January 25th, 2013:Wuhan Wuhan University, deposit number is：
CCTCC NO：M 2013055.
The purposes of described bacterial strain is, by tangerine green trichoderma（Trichoderma citrinoviride.）IBPT-4 carries out sending out
Ferment is cultivated, and mycelium and fermentation broth extract are isolated to that to have the compound of tumor cell proliferation inhibition activity be penem
Alcohol E1.
This structural formula of compound is：
.
Its architectural feature is：Molecular skeleton containing five cyclic amides, connect ten carbon saturations containing carbonyl
One methyl is connected on fatty long-chain, N, molecule has two oh groups.
The present invention also protects described compound to suppress the purposes in medicine in preparation for proliferation of human gastric cancer cell, and should
Purposes in preparation anti-gastric cancer medicament for the compound.
The remarkable advantage of the present invention：This compound shown in research is the novel alkaloid of a structure, described alkaloids
Compound has significant anti-gastric cancer activity, has not yet to see the chemical constitution of this compound and for proliferation of human gastric cancer cell suppression
The report of activity, also there is not yet medicine related to this therefore on market.
Brief description
Fig. 1 is the main COSY and HMBC signal of mould enol E1.
Specific embodiment
The chemical constitution of the compound of indication in examples below：
.
The fermenting and producing of this compound of embodiment 1 and separation and purification
1 fermenting and producing
Produce the fermented and cultured of bacterium：By the conventional method of culture microorganism, take tangerine green trichoderma（Trichoderma
citrinoviride.）IBPT-4 (is deposited in China typical culture collection center, address on January 25th, 2013:Military
Chinese Wuhan University, deposit number is：CCTCC NO：M 2013055) appropriate, it is inoculated on PDA solid slope culture medium 28
Cultivate 4 days in DEG C incubator.
Take the inclined-plane culture tangerine green trichoderma of 4 days（Trichoderma citrinoviride.）Appropriate IBPT-4, is inoculated into
Equipped with 400mL nutrient solution, [nutrient solution forms (g/l)：Mannitol 20.0, yeast extract 3.0, maltose 20.0, monosodium glutamate 10.0,
Glucose 10.0, KH2PO40.5, MgSO40.3, NaCL 6.0 constant volume] 1000mL conical flask in, 28 DEG C of static gas wave refrigerator
After 30 days, obtain mycelium and zymotic fluid.
The acquisition of 2 medicinal extract
With gauze by mycelium and separation of fermentative broth.By zymotic fluid and ethyl acetate 1:2（v/v）It is extracted twice, extract reduces pressure
Distill to dry, obtain the ethyl acetate extract of zymotic fluid.Mycelium is then with the aqueous solution ultrasonication containing 70wt%-80wt% acetone
3 times, remove reduced pressure concentration after clear liquid is merged by residue and remove acetone, with being 1 by volume:2 addition ethyl acetate are extracted twice,
It is evaporated to dry mycelium medicinal extract.The total medicinal extract of extract is obtained after mycelium and zymotic fluid medicinal extract are merged.
The separation and purification of 3 compounds
This medicinal extract after 100-200 mesh silica gel mixed sample, with petroleum ether：Dichloromethane：Methyl alcohol is eluent decompression silica gel color
Spectrum post gradient elution.Eluent is followed the tracks of through activity, obtains active component B (methylene chloride-methanol v/v 50:1 eluate),
Then with petroleum ether：Dichloromethane：Methanol gradient group is divided into eluant, eluent, passes through pressurized silica gel column chromatography gradient elution further,
(methylene chloride-methanol is 20 to the active subfraction B1 obtaining:1 eluate) with chloroform-methanol (v/v1:2) carry out for solvent
Sephadex LH-20 gel filtration chromatography, finally by semi-preparative liquid chromatography (1010 types ODS-A, 10 × 250 mm, 5 μm)：
Separating flow velocity is 5 mL/min, and mobile phase is that 85% acetonitrile contains 0.1% TFA, obtains shown compound（32.1 mg,t R
20.7min）.
Compound pale yellow oil, high resolution mass spectrum HRESI-MS provides molecular ion peak at m/z 324.2161
[M – H]–, (Calcd for C18H30NO4, 324.2175), point out molecular weight to be 325, speculate molecular formula in conjunction with spectral information
For C18H31NO4.1H and13The NMR data such as C-NMR are shown in Table 1.
Table 1 compound1H and13C-NMR data (500 MHz, in CDCl3)a)
A) this table signals assignment is based on DEPT, HMQC and HMBC spectrum analysis result.The species of carbon signal utilizes DEPT method true
Fixed.
The test of embodiment 2 anti tumor activity in vitro
1 laboratory sample and experimental technique
The preparation test sample of sample solution is the pure compounds of separation and purification in above-mentioned enforcement 1.Precision weighs in right amount
Sample, is configured to the solution of desired concn with methyl alcohol, for surveying activity.
The squamous subculture of clone and cell adopts gastric carcinoma cell lines, and stomach cancer cell is trained with the RPMI-1640 containing 10% FBS
Foster base, in 37 DEG C of squamous subculture in the incubator being passed through 5% carbon dioxide.
Cell inhibitory effect activity test method
Tetrazolium（MTT）Method is taken the logarithm the cell in growth period, and cell density is adjusted to every milliliter 2 × 105Individual cell, by every
200 microlitres of hole is inoculated in 96 porocyte culture plates, is passed through 5% CO in 37 DEG C2Incubator in cultivate 4 hours.Every hole adds 2
Microlitre sample liquid or blank solution, after culture 24 hours, every hole adds MTT liquid（5 milligrams of normal saline solutions of every milliliter of MTT）10
Microlitre, continue culture 4 hours, 37 DEG C, 2000 revs/min are centrifuged 8 minutes, suck supernatant.Every hole adds each 100 microlitres of DMSO,
Micro oscillator vibrates 15 minutes, after being completely dissolved to crystallization, produces SPECTRAMAX Plus type enzyme mark using MD company
Instrument measures light absorption value at 570nm for every hole（OD）Value.In same 96 orifice plate, each concentration of sample is respectively provided with three holes, separately
If three hole blanks and acellular zeroing hole（If medicine has color will do the acellular zeroing of relative medicine concentration）.Each hole OD
Value first does accordingly acellular zeroing, then takes three hole mean OD value by IR (%)=(ODBlank-ODSample)/ODBlank× 100%
Formula calculates cell proliferation inhibition rate (IR%) under each concentration.
2. experimental result
Cell inhibitory effect active testing result
In mtt assay test, the proliferation of human gastric cancer cell inhibiting rate of this compound according to variable concentrations, apply SPSS16.0 software
Carry out data processing calculation of half inhibitory concentration IC50Value.The results are shown in Table 2.
The inhibitory activity to proliferation of human gastric cancer cell for table 2 compound
3. conclusion
Compound has obvious Approach of gastric carcinoma cells proliferation inhibited, can be used as preparing proliferation of human gastric cancer cell inhibitor or anti-gastric cancer
Medicine is used for antineoplastic research.
Claims (2)
1. a kind of application of mould enol E1 coming from tangerine green trichoderma is it is characterised in that the structural formula of described mould enol E1 is, described mould enol E1 be applied to proliferation of human gastric cancer cell suppress medicine in system
Standby.
2. a kind of application of mould enol E1 coming from tangerine green trichoderma is it is characterised in that the structural formula of described mould enol E1 is, described mould enol E1 is applied to the preparation in anti-gastric cancer medicament.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610819719.7A CN106389417B (en) | 2016-09-13 | 2016-09-13 | Derived from application of the mould enol E1 in terms of gastric cancer of tangerine green trichoderma |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610819719.7A CN106389417B (en) | 2016-09-13 | 2016-09-13 | Derived from application of the mould enol E1 in terms of gastric cancer of tangerine green trichoderma |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106389417A true CN106389417A (en) | 2017-02-15 |
| CN106389417B CN106389417B (en) | 2019-06-07 |
Family
ID=58000040
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610819719.7A Expired - Fee Related CN106389417B (en) | 2016-09-13 | 2016-09-13 | Derived from application of the mould enol E1 in terms of gastric cancer of tangerine green trichoderma |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106389417B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110136752A1 (en) * | 2009-12-04 | 2011-06-09 | Novobiotic Pharmaceuticals Llc | Novel antibiotics |
| CN103865808A (en) * | 2014-03-10 | 2014-06-18 | 福州大学 | Novel anti-tumor application of penicillium enol A1 from penicillium citrinum |
-
2016
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110136752A1 (en) * | 2009-12-04 | 2011-06-09 | Novobiotic Pharmaceuticals Llc | Novel antibiotics |
| CN103865808A (en) * | 2014-03-10 | 2014-06-18 | 福州大学 | Novel anti-tumor application of penicillium enol A1 from penicillium citrinum |
Non-Patent Citations (2)
| Title |
|---|
| LI CHEN等: "TUMONOIC ACIDS K AND L, NOVEL METABOLITES FROM THE MARINE-DERIVED FUNGUS PENICILLIUM CITRINUM", 《HETEROCYCLES》 * |
| ZHEN-JIAN LIN等: "Penicillenols from Penicillium sp. GQ-7, an Endophytic Fungus Associated with Aegiceras corniculatum", 《CHEM. PHARM. BULL.》 * |
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| Publication number | Publication date |
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| CN106389417B (en) | 2019-06-07 |
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