CN105001228B - Application of penicillium citrinum-derived penicitrinine A in preparing drugs for treating human oral epidermoid tumor - Google Patents
Application of penicillium citrinum-derived penicitrinine A in preparing drugs for treating human oral epidermoid tumor Download PDFInfo
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- 241000228153 Penicillium citrinum Species 0.000 title abstract description 10
- 229940079593 drug Drugs 0.000 title abstract description 5
- 206010028980 Neoplasm Diseases 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 26
- 230000004663 cell proliferation Effects 0.000 claims abstract description 7
- 241000228212 Aspergillus Species 0.000 claims description 10
- 229930013930 alkaloid Natural products 0.000 claims description 10
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 6
- -1 alkaloid compound Chemical class 0.000 claims description 5
- 238000000855 fermentation Methods 0.000 abstract description 9
- 230000004151 fermentation Effects 0.000 abstract description 9
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- 230000002401 inhibitory effect Effects 0.000 abstract description 7
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- 238000002474 experimental method Methods 0.000 abstract description 2
- 241000228143 Penicillium Species 0.000 abstract 1
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
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- 238000000926 separation method Methods 0.000 description 8
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- 238000002360 preparation method Methods 0.000 description 6
- 150000003797 alkaloid derivatives Chemical class 0.000 description 5
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- 239000012531 culture fluid Substances 0.000 description 4
- 239000000824 cytostatic agent Substances 0.000 description 4
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- 239000003480 eluent Substances 0.000 description 4
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- 239000002585 base Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 3
- 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 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 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 2
- 239000007836 KH2PO4 Substances 0.000 description 2
- 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 2
- 229930195725 Mannitol Natural products 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 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
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000005100 correlation spectroscopy Methods 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 239000002024 ethyl acetate extract Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
- LPUQAYUQRXPFSQ-DFWYDOINSA-M monosodium L-glutamate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCC(O)=O LPUQAYUQRXPFSQ-DFWYDOINSA-M 0.000 description 2
- 235000013923 monosodium glutamate Nutrition 0.000 description 2
- 239000004223 monosodium glutamate Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 238000004262 preparative liquid chromatography Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000003068 static effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000001154 Dermoid Cyst Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 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
- 239000003513 alkali Substances 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 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
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001603 reducing effect Effects 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/20—Spiro-condensed systems
-
- 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
- C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Wood Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
The invention discloses an alkaloidal compound penicitrinine A derived from penicillium citrinum, and the application of the penicillium citrinum-derived penicitrinine A in preparing drugs for inhibiting the cell proliferation of human oral epidermoid tumor cells or antitumor drugs. The structural formula of the penicitrinine A is shown in img file='dest_path_image002.TIF' wi='251' he='135'. After the fermental cultivation of penicillium citrinum ((i) Penicillium (/i)(i) citrinum (/i)) IBPT-5, fermentation products are obtained, separated and purified to obtain the above compound. The results of experiments show that, the compound is better in antitumor activity for human oral epidermoid tumor cells KB. Therefore, the compound can be used for preparing drugs for inhibiting the cell proliferation of human oral epidermoid tumor cells or antitumor drugs.
Description
Technical field
The invention belongs to antitumor drug preparation field, and in particular to a kind of alkaloid compound for coming from Aspergillus citrimum
Penicitrinine A and its application in preparation human mouth epidermoidoma cytostatic thing or antitumor drug.
Background technology
Alkaloid is the organic compounds containing nitrogen that a class is produced by biological cometabolism, the alkaloid species in nature compared with
It is many, mostly from plant, therefore and there is the title of plant alkaloid.Alkaloid has important physiological action to humans and animals, including flat
Antitussive, blood sugar lowering, blood fat reducing, antibacterial, antitumor, analgesia etc. is breathed heavily, is wherein projected with antibacterial, anti-tumor activity the most.Natural knot
Structure alkaloid is the important sources of discovery lead compound in innovation drug research, has been applied to the alkaloidal drug of clinic at present
Nearly hundred kinds of Jing.Research finds that some marine fungis can produce the biology that structure is novel, activity is good during cometabolism
Alkali, with good medicinal and industrialization prospect.
The present inventor studies and learns, Aspergillus citrimum (Penicillium citrinum) IBPT-5, (in 2013 12
The moon is deposited in China typical culture collection center, address on 25th:Wuhan Wuhan University, deposit number is：CCTCC NO：M
2013713) crude extract of tunning has good cell inhibitory effect activity, and then its active component is studied.
Research finds that shown alkaloid compound has anti-human oral epidermoid carcinoma activity, has not yet to see the compound to human mouth
The report of the proliferation inhibition activity of epidermoidoma cell KB, therefore also there is not yet medicine related to this on market.
The content of the invention
It is an object of the invention to provide a kind of alkaloid compound penicitrinine A for coming from Aspergillus citrimum and its
Preparing human mouth epidermoidoma cytostatic thing or the application in antitumor drug.The compound has suppression population
Chamber epidermoidoma cel l proliferation, with anti-human oral epidermoid carcinoma activity.
The structural formula of the compound is：
。
The preparation method of the compound be by fermentation culture Aspergillus citrimum (Penicillium citrinum) IBPT-5,
Fermented product is obtained, the compound is then isolated and purified out from fermented product.Comprise the following steps that：
1st, fermenting and producing
The conventional method of cultivating microorganism, take Aspergillus citrimum (Penicillium citrinum) IBPT-5 is inoculated into PDA
Cultivate 4 days in 28 DEG C of incubators on solid slant culture base, be then seeded in culture fluid, 28 DEG C of static gas wave refrigerators are after 30 days,
Obtain mycelium and fermentation liquid；The culture fluid composition：Every liter of water contains 20.0 g of Mannitol, 3.0 g of yeast extract, maltose 20.0
G, 10.0 g of monosodium glutamate, glucose 10.0 g, KH2PO4 0.5 g、MgSO40.3 g、NaCl 30.0 g；
2nd, the acquisition of extractum
With gauze by mycelium and separation of fermentative broth.By fermentation liquid ethyl acetate 1:2 (v/v) are extracted twice, extract
Vacuum distillation obtains 32.0 g of ethyl acetate extract of fermentation liquid to dry.
3rd, the separation and purification of compound
The extractum after 100-200 mesh silica gel mixed samples, with petroleum ether：Dichloromethane：Methanol is eluent decompression silicon
Glue chromatographic column gradient elution, obtains 11 components.Component 7 (4.2 g) (dichloromethane：Methanol v/v=100:1 eluate)
With dichloromethane：Methanol is eluent, further by pressurized silica gel column chromatography gradient elution, the subfraction 7-6 (two for obtaining
Chloromethanes：Methanol v/v=50:1 eluate) by semi-preparative liquid chromatography (1010 types ODS-A, 10 × 250 mm, 5 μm)：
Separation flow velocity is 5 mL/min, and mobile phase is that 75% acetonitrile contains 0.1% TFA, obtains shown compound (97.9 mg, tR 19.3
min)。
Aspergillus citrimum (the Penicillium citrinum) IBPT-5, is deposited in China on December 25th, 2013
Type Tissue Collection, address:Wuhan Wuhan University, deposit number is：CCTCC NO：M 2013713.
The compound is preparing the purposes in suppressing human mouth epidermoidoma cell proliferation, and the compound in preparation
Purposes in anti-human oral epidermoid carcinoma medicine.The tumor cell behaviour oral epidermoid carcinoma cell KB.
The present invention remarkable advantage be：The alkaloid compound shown in research is more rare, the alkaloidss chemical combination
Thing has significant suppression human mouth epidermoidoma cell-proliferation activity, has not yet to see the compound to human mouth epidermoidoma
The report of cell KB proliferation inhibition activities, therefore also there is not yet medicine related to this on market.
Description of the drawings
Fig. 1 is the main COSY of Penicitrinine A, HMBC and NOESY signals.
Specific embodiment
The chemical constitution of the compound of indication in examples below：
。
The fermenting and producing of 1 compound of embodiment and separation and purification
1st, fermenting and producing
The fermentation culture of production bacterium：By the conventional method of cultivating microorganism, Aspergillus citrimum is taken（Penicillium citrinum）IBPT-5 (is deposited in China typical culture collection center, address on December 25th, 2013:Wuhan is military
Chinese university, deposit number is：CCTCC NO：M is 2013713) appropriate, is inoculated on PDA solid slant culture bases and trains at 28 DEG C
Cultivate 4 days in foster case.
Take the slant culture Aspergillus citrimum of 4 days（Penicillium citrinum）Appropriate IBPT-5, is inoculated into equipped with 400mL
[culture fluid constitutes (g/l) to culture fluid：Mannitol 20.0, yeast extract 3.0, maltose 20.0, monosodium glutamate 10.0, glucose
10.0, KH2PO40.5, MgSO40.3, NaCl 30.0 constant volume] 1000mL conical flasks in, 28 DEG C of static gas wave refrigerators 30 days
Afterwards, mycelium and fermentation liquid are obtained.
2nd, the acquisition of extractum
With gauze by mycelium and separation of fermentative broth.By fermentation liquid ethyl acetate 1:2 (v/v) are extracted twice, extraction
Liquid vacuum distillation obtains 32.0 g of ethyl acetate extract of fermentation liquid to dry.
3rd, the separation and purification of compound
The extractum after 100-200 mesh silica gel mixed samples, with petroleum ether：Dichloromethane：Methanol is eluent decompression silicon
Glue chromatographic column gradient elution, obtains 11 components.Component 7 (4.2 g) (dichloromethane：Methanol v/v=100:1 eluate)
With dichloromethane：Methanol is eluent, further by pressurized silica gel column chromatography gradient elution, the subfraction 7-6 (two for obtaining
Chloromethanes：Methanol v/v=50:1 eluate) by semi-preparative liquid chromatography (1010 types ODS-A, 10 × 250 mm, 5 μm)：
Separation flow velocity is 5 mL/min, and mobile phase is that 75% acetonitrile contains 0.1% TFA, obtains shown compound (97.9 mg, tR 19.3
min)。
In yellow oily, high resolution mass spectrum HRESI-MS's compound existsm/z484.2711 place provides molecular ion peak [M
H]–, (calcd. for C28H38NO6, 484.2705), point out molecular weight to be 485, speculate that molecular formula is with reference to spectral information
C28H39NO6。1H and13C-NMR data are shown in Table 1, and main COSY, HMBC and NOESY signals are shown in Fig. 1.
1 NMR compounds of table1H and13C-NMR data (500MHz1H and 125MHz 13C, in CDCl3)
The test of 2 anti tumor activity in vitro of embodiment
1st, 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.It is accurate to claim
Appropriate amount of sample is taken, the solution of desired concn is configured to DMSO, for surveying activity.
The successive transfer culture of cell line and cell adopts tumor cell line, tumor cell to be trained with the RPMI 1640 containing 10% FBS
Foster base, at 37 DEG C in being passed through 5% CO2Incubator in successive transfer culture.
Cell inhibitory effect activity test method
WST-1 methods are taken the logarithm the tumor cell of trophophase, and cell density is adjusted to per milliliter 5 × 104Individual cell, by every
100 μ L of hole are inoculated in 96 porocyte culture plates, are passed through 5% CO in 37 DEG C2Incubator in overnight incubation.Suck supernatant,
The 100 μ L of culture medium containing sample are added, continues 48 h of culture.10 μ L WST-1 liquid are added per hole, cultivate 4 h.Using Bio-
Rad companies produce 680 type microplate reader and determine per light absorption value (OD) value of the hole at 450nm.In 96 orifice plate of same, sample is every
Individual concentration is respectively provided with five holes, separately sets five hole blanks and acellular zeroing hole (if to have color do relative medicine dense for medicine
Spend acellular zeroing).Each hole OD values first do corresponding acellular zeroing, then take five hole mean OD values by IR (%)=(ODBlank-
ODSample)/ODBlank× 100% formula calculates cell proliferation inhibition rate (IR%) under each concentration.
2nd, experimental result
Cell inhibitory effect active testing result
In the test of WST-1 methods, according to the Cytostatic to tumor cell rate of the compound of variable concentrations, application
SPSS16.0 softwares carry out data processing calculation of half inhibitory concentration IC50Value.The results are shown in Table 2.
Inhibitory activity of 2 compound of table to human mouth epiderm-like tumor cell proliferation
3. conclusion
The compound has preferable anti-tumor activity to human mouth epidermoidoma cell KB.Can be used as preparation human mouth table
Dermoid tumor cytostatic thing or antitumor drug are used for the research of human mouth epidermoidoma.
The foregoing is only presently preferred embodiments of the present invention, all impartial changes done according to scope of the present invention patent with
Modification, should all belong to the covering scope of the present invention.
Claims (3)
1. the alkaloid compound penicitrinineA of Aspergillus citrimum is come from, it is characterised in that structural formula is as follows：
。
2. a kind of compound as claimed in claim 1 prepare suppress human mouth epidermoidoma cell proliferation in should
With.
3. application of a kind of compound as claimed in claim 1 in anti-human oral epidermoid carcinoma medicine is prepared.
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|---|---|---|---|
| CN201510423834.8A CN105001228B (en) | 2015-07-17 | 2015-07-17 | Application of penicillium citrinum-derived penicitrinine A in preparing drugs for treating human oral epidermoid tumor |
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|---|---|---|---|
| CN201510423834.8A CN105001228B (en) | 2015-07-17 | 2015-07-17 | Application of penicillium citrinum-derived penicitrinine A in preparing drugs for treating human oral epidermoid tumor |
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| PL213646B1 (en) * | 2002-06-20 | 2013-04-30 | Astion Dermatology A/S | Novel complexes of fatty acid esters of polyhydroxyalkanes and pyridine carboxy derivatives |
| WO2006075395A1 (en) * | 2005-01-11 | 2006-07-20 | The Kitasato Institute | β-LACTAM ANTIBIOTIC ACTIVITY ENHANCER AND PROCESS FOR PRODUCING THE SAME |
| CN104478891B (en) * | 2014-12-18 | 2016-08-24 | 福州大学 | Citrinin compounds penicitrinol O coming from Aspergillus citrimum and its preparation method and application |
| CN104592082B (en) * | 2014-12-18 | 2016-10-05 | 福州大学 | Preparation method and application of penicillol D2 derived from Penicillium citrinum |
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