CN108660082A - A kind of marine aspergillus source oxa- anthraquinone analog compound and preparation method thereof and the application in preparing antiseptic - Google Patents

A kind of marine aspergillus source oxa- anthraquinone analog compound and preparation method thereof and the application in preparing antiseptic Download PDF

Info

Publication number
CN108660082A
CN108660082A CN201810623511.7A CN201810623511A CN108660082A CN 108660082 A CN108660082 A CN 108660082A CN 201810623511 A CN201810623511 A CN 201810623511A CN 108660082 A CN108660082 A CN 108660082A
Authority
CN
China
Prior art keywords
aspergillus
oxa
marine
analog compound
anthraquinone analog
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201810623511.7A
Other languages
Chinese (zh)
Other versions
CN108660082B (en
Inventor
曹飞
朱华结
朱奡
刘云凤
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Heibei University
Original Assignee
Heibei University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Heibei University filed Critical Heibei University
Priority to CN201810623511.7A priority Critical patent/CN108660082B/en
Publication of CN108660082A publication Critical patent/CN108660082A/en
Application granted granted Critical
Publication of CN108660082B publication Critical patent/CN108660082B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/645—Fungi ; Processes using fungi
    • C12R2001/66—Aspergillus
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/14—Fungi; Culture media therefor
    • C12N1/145—Fungal isolates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-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
    • C12P17/181—Heterocyclic compounds containing oxygen atoms as the only ring heteroatoms in the condensed system, e.g. Salinomycin, Septamycin

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Mycology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Botany (AREA)
  • Veterinary Medicine (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Virology (AREA)
  • Biomedical Technology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Application the present invention provides a kind of marine aspergillus source oxa- anthraquinone analog compound and preparation method thereof and in preparing antiseptic, the marine aspergillus are aspergillus（Aspergillus sp.）01 bacterial strains of ZA, the deposit date is on January 25th, 2018, deposit number was CGMCC No.15270, and depositary institution is China Committee for Culture Collection of Microorganisms's common micro-organisms center, and depositary institution address is Yard 1, BeiChen xi Road, Chaoyang District, Beijing City 3.The structural formula of the compound is, wherein R independently is OH or OAc.Pass through fermented and cultured aspergillus（Aspergillus sp.）01 bacterial strains of ZA, and the isolated above compound from tunning, verified, the compounds of this invention has compared with strong inhibitory activity a variety of pathogens, can be made into antiseptic, be with a wide range of applications.

Description

It a kind of marine aspergillus source oxa- anthraquinone analog compound and preparation method thereof and is preparing Application in antiseptic
Technical field
The present invention relates to marine natural medicinal chemistry arts, relate in particular to a kind of marine aspergillus source oxa- Anthraquinones Compound and preparation method thereof and the application in preparing antiseptic.
Background technology
Ocean accounts for about the 71% of earth total surface area, has contained rich and varied living resources, is that the mankind carry out drug The precious resources library of research and development.Since the 1940s, using cephalosporin, cytarabine and ET-743 as a variety of of representative Marine source drug is by Successful utilization to clinically.Marine-derived fungal microbial resources are because its metabolite enriches and can The advantages that repeating to ferment becomes one of most important source of marine drug, wherein with the oxa- Anthraquinones in marine fungi source Close the important topic that the active compound for anti tumor that object is representative has become modern marine drug research.
Currently, the type for the marine fungi source oxa- anthraquinone analog compound reported is limited, and its antibacterial activity is ground Study carefully it is less, at present there has been no about oxa- anthraquinone analog compound of the present invention and its resist a variety of active reports of pathogen.
Invention content
An object of the present invention is just to provide a kind of marine aspergillus source oxa- anthraquinone analog compound and preparation method thereof, To solve the problems, such as that the type of marine fungi source oxa- anthraquinone analog compound and antibacterial activity are limited in the prior art.
The second object of the present invention is just to provide a kind of marine aspergillus source oxa- anthraquinone analog compound and is preparing antiseptic In application.
The purpose of the present invention is what is be achieved through the following technical solutions：A kind of marine aspergillus, the marine aspergillus are aspergillus (Aspergillus sp.) ZA-01 bacterial strains, the deposit date is on January 25th, 2018, deposit number was CGMCC No.15270, Depositary institution is China Committee for Culture Collection of Microorganisms's common micro-organisms center, and depositary institution address is Beijing's southern exposure The institute 3 of area North Star West Road 1.
1. sample source
Marine aspergillus ZA-01 strain isolations pick up from river from marine sediment, the marine sediment sample in June, 2015 The Cangzhou Cities Bei Sheng PORT OF HUANGHUA marine site.It after bottom sediment sample collection, is put in -20 DEG C of refrigerators and preserves at once, and be sent to experiment Room carries out the mask work of follow-up fungi.
2. the separation of fungi
The selection of 2.1 culture mediums
(1) PDA culture medium
Potato (peeling) 200g, glucose 20g, sea salt 30g, agar 20g, water 1000mL.Add 25 μ when detaching fungi G/mL streptomycin sulphates, 25 μ g/mL ampicillins inhibit bacterial growth.
(2) salt-free PDA culture medium
Potato (peeling) 200g, glucose 20g, agar 20g, water 1000mL.Add 25 μ g/mL sulfuric acid when detaching fungi Streptomysin, 25 μ g/mL ampicillins inhibit bacterial growth (salt-free PDA is compared with salt PDA is added).
(3) rose bengal medium
Potato (peeling) 200g, glucose 20g, sea salt 30g, rose-bengal (rose Bengal) 33mg (inhibit life Long fast mould sprawling growth), agar 20g, water 1000mL.
Separation, the purifying of 2.2 fungies
Above-mentioned marine sediment sample is placed in sterile glass device, 1mL sterile waters are added and are adjusted to sticky shape.It takes out 0.1mL aforesaid liquids dilute 10 times, 100 times, 1000 times with sterile water respectively, the homogenate of 4 concentration gradients are obtained, with nothing Bacterium pipette takes each concentration homogenates of 0.2mL to be separately added into PDA, salt-free PDA, rose bengal medium respectively, uses spreader It smoothens.Each concentration gradient do respectively three it is parallel.It is sealed with sealed membrane, and writes number.The above separating experiment is sterile Under the conditions of carry out.
The culture medium of above-mentioned addition sample is respectively put into 28 DEG C of insulating boxs, is inverted culture.5-8d of general culture just have bacterium It falls either mycelium and grows (bacterial growth is fast, and 2-3d just have bacterium colony to grow out) from culture medium or the small block edge of tissue. It with transfer needle picking colony or mycelium tip, moves on new tablet, after isolating and purifying several times, it is pure to can get fungi Bacterial strain.Fungi mask work generally carries out 35d.The last fortnight checks once daily, is checked later every 3-4d primary.Once hair Existing new bacterium colony or mycelium are grown, and should be transferred on new tablet at once.
3, the screening of bacterial strain
Aimed strain is screened using the method for screening active ingredients combination Chemical Screening.By being fermented on a small scale to bacterial strain (2 bottles), obtain coarse extract, to coarse extract carry out antibacterial activity test, using to the inhibitory activity of pathogenic bacteria as screen object bacteria One of the investigation factor of strain；And HPLC fingerprint map analyzings are carried out to coarse extract, using secondary metabolite amount as screening target The two of the investigation factor of bacterial strain, the final bacterial strain ZA-01 for determining that bacteriostatic activity is high and secondary metabolite is abundant is object bacteria Strain, and it is identified.
4, the identification of bacterial strain
3-7d is cultivated on PDA medium plate, grows to the fungi of optimum state, in sterilizing pipette tips picking single bacterium colony In a small amount of mycelia to the EP pipes equipped with 50 μ L Lysis buffer (lysate), the thermal denaturation 15min in 80 DEG C of water-baths, so 8000 rpm centrifuge 1min afterwards, and it is the template DNA of PCR reactions to take 3 μ L supernatants.
Primer for expanding and being sequenced is ITS1 and ITS4, and upper and lower primer sequence is：
ITS1：TCCGTAGGTGAACCTGCGG
ITS4：TCCTCCGCTTATTGATATGC
PCR reaction systems are 40 μ L systems, including：
Amplification condition is：
0.8% Ago-Gel of amplified production, 0.5 × TBE electrophoretic buffer samples, 5V/cm voltages, 5 μ L electricity of loading Swimming detection, DNA Marker indication molecule amounts, gel imager are observed and are taken a picture.Beijing three is sent to win Radix Polygalae pcr amplification product Company is sequenced, and is finally accredited as marine aspergillus (Aspergillus sp.).
A kind of marine aspergillus source oxa- anthraquinone analog compound, the structural formula of the compound are
Wherein, R independently is OH or OAc.
The compound is
A kind of preparation method of above-mentioned marine aspergillus source oxa- anthraquinone analog compound, includes the following steps：
(1) by marine aspergillus described in claim 1 (Aspergillus sp.) ZA-01 inoculations in Spawn incubation Spawn incubation is carried out in base；
(2) it after the completion of Spawn incubation, is inoculated in fermentation medium and is fermented, obtain fermentate；
(3) extraction 2-4 times is carried out to fermentate with ethyl acetate, is concentrated under reduced pressure to give after combined ethyl acetate extract liquor thick Medicinal extract；
(4) chromatographic isolation is carried out up to the oxa- anthraquinone analog compound to gained coarse extract, the chromatographic isolation is Normal phase silica gel column chromatography separation, reversed-phase silica gel column chromatography separation, gel column chromatography separation and high performance liquid chromatography point are carried out successively From.
Bacterium culture medium is described in step (1)：1.0-10wt% of glucose, 0.1-4.0wt% of yeast extract, peptone 0.2-4.0wt%, 1.0-6.0wt% of agar, 3.0-10wt% of coarse sea salt, remaining is water；Spawn incubation temperature is 15-35 DEG C, Incubation time is 3-10 days.
The fermentation medium of per unit part includes 60-150g of rice, NaNO in step (2)3 0.1–0.6g、KH2PO4 0.05–0.2g、MgSO4·7H2O 0.02–0.1g、NaCl 0.02–0.1g、FeSO40.01-0.05g, 2-6g of sucrose, water 50–150mL；Fermentation culture conditions are stationary culture 20-50 days at 15-35 DEG C.
Normal phase silica gel column chromatography is separated into described in step (4)：First use stationary phase for 100~200 mesh silica gel, mobile phase It is eluted for 15-25vol% ethyl acetate/petroleum ether mixed solutions, elution volume is 3-5 column volume, and gained is eluted Use stationary phase for 200~300 mesh silica gel again after liquid concentration, mobile phase is 65-75vol% methylene chloride/methanol mixed solutions It is eluted, elution volume is 2-3 column volume.
The stationary phase that the separation of reversed-phase silica gel column chromatography described in step (4) uses is C18Silica gel, mobile phase are 60- 70vol% methanol/water mixed solutions, elution volume are 2-3 column volume.
The stationary phase of the separation of gel column chromatography described in step (4) is sephadex LH-20, and mobile phase is dichloromethane, Elution volume is 3-5 column volume.
The chromatographic column used in high performance liquid chromatography separation described in step (4) prepares C for half18Chromatographic column, XBridge OBD, 5 μm, 10 × 250mm, mobile phase is the methanol/water mixed solution of 75-80vol%；Silica gel chromatographic column is partly prepared, ViridisTMSilica 2-Ethylpyridine, 5 μm, 10 × 250mm, mobile phase is mixed for 80-85vol% petroleum ethers/ethyl alcohol Close solution.
A kind of application of marine aspergillus source oxa- anthraquinone analog compound in preparing antiseptic, the antiseptic is with above-mentioned Compound or its pharmaceutically acceptable salt be active ingredient.
The above-mentioned oxa- anthraquinone analog compound or its pharmaceutically acceptable salt in a kind of marine aspergillus source prevent preparing And/or treatment is by micrococcus lysodeikticus (Micrococcus lysodeikticus), bacillus anthracis (Bacillus Anthraci), Salmonella typhi (Salmonella typhi) and clostridium perfringen (Enterobacter aerogenes) are drawn Application in the drug of the bacteriosis risen.
Term " pharmaceutically acceptable salt " refers to the addition of atoxic inorganic or organic acid and/or alkali in the present invention Salt, reference can be made to " Salt selection for basic drugs ", Int.J.Pharm. (1986), 33,201-217.
The present invention obtains oxa- anthraquinone analog compound 7 and 8 by marine fungi ZA-01 strain fermentations, to micrococcus lysodeikticus (Micrococcus lysodeikticus), bacillus anthracis (Bacillus anthraci), Salmonella typhi (Salmonella Typhi) and clostridium perfringen (Enterobacter aerogenes) has preferable inhibitory activity, can be used as antiseptic, answers With having a extensive future.
Specific implementation mode
Embodiment 1
(1) culture of marine fungi ZA-01 strains
Culture medium used in the Spawn incubation of marine fungi ZA-01 contains glucose 1.0wt%, yeast extract 0.1wt%, egg White peptone 0.2wt%, agar 1.0wt%, coarse sea salt 3.0wt%, remaining is water, and test tube slant, marine fungi is made in when use ZA-01 bacterial strains are cultivated 3 days at 28 DEG C.
(2) fermented and cultured of marine fungi ZA-01
Fermentation medium used in the fermented and cultured of marine fungi ZA-01 is to contain rice in each 1000mL conical flasks 60g、 NaNO3 0.1g、KH2PO4 0.05g、MgSO4·7H2O 0.02g、NaCl 0.02g、FeSO40.01g, sucrose 2g, Water 50mL, bacterial strain are cultivated 28 days in 28 DEG C of standing for fermentation, obtain fermentate；80 1000mL conical flasks are used to ferment altogether.
(3) the separation analysis of oxa- anthraquinone analog compound
The fermentate obtained by step (2) is taken, is extracted with ethyl acetate 2 times, combined ethyl acetate extract liquor is concentrated under reduced pressure To coarse extract, normal phase silica gel column chromatography separation, stationary phase are first carried out：100~200 mesh silica gel, mobile phase are 15vol% acetic acid Ethyl ester/petroleum ether mixed solution elutes 5 column volumes, normal phase silica gel column chromatography separation is carried out again after eluent concentration, Gu Determine phase：200~300 mesh silica gel, mobile phase are the methylene chloride/methanol mixed solution of 65vol%, elute 2 column volumes.
Reversed-phase silica gel column chromatography separation is carried out after eluent concentration, stationary phase is preferably C18Silica gel, mobile phase are preferably 60vol% methanol/water mixed solutions elute 3 column volumes.Sephadex LH20 gel column chromatographies are carried out after eluent concentration Separation, mobile phase：Dichloromethane elutes 3 column volumes, high performance liquid chromatography separation, stationary phase is carried out after eluent concentration： Half prepares C18Chromatographic column, XBridge OBD, 5 μm, 10 × 250mm, mobile phase is the methanol/water mixed solution of 75vol%, and Partly prepare silica gel chromatographic column, ViridisTMSilica 2-Ethylpyridine, 5 μm, 10 × 250mm, mobile phase is Petroleum ether/alcohol mixed solution of 80vol%, preparative separation obtain compound 1 (15.0mg), compound 2 (4.5mg), 3 (5.0mg), 4 (5.2 mg), 5 (5.0mg), 6 (4.5mg), 7 (5.0mg), 8 (4.7mg), structural identification data difference are as follows：
Compound 1Yellow amorphous powder；[α]D 20-97(c 0.1,MeOH)；IR(KBr) νmax 3445,2929,2355,1635,1591,1475,1246,1065,895cm–1；1H NMR(CDCl3,600Hz)δ:12.97 (1H, brs, 1-OH), 7.66 (1H, d, J=8.4Hz, H-3), 7.24 (1H, s, H-5), 6.89 (1H, brs, H-25), 6.82 (1H, d, J=8.4Hz, H-2), 5.10 (1H, brs, H-14), 4.80 (1H, s, Ha-22), 4.75 (1H, s, Hb-22), 4.54 (1H, brd, J=10.8 Hz, Ha-19), 4.31 (1H, dd, J=10.8,2.4Hz, Hb-19), 3.45 (1H, brs, H-15), 3.28(1H,s,14-OCH3), 2.73(1H,brs,15-OH),2.71(1H,brs,H-20),2.35(3H,s,H-24),2.07 (3H,s,25-OAc),1.88(3H,s, H-23),1.40(3H,s,H-18),1.25(3H,s,H-17).13C NMR(CDCl3, 150MHz)δ:183.0(C,C-13), 170.0(C,25-COOCH3),161.7(C,C-1),152.2(C,C-10),151.5 (C,C-11),150.2(C,C-7),141.5(C, C-21),137.6(C,C-6),135.3(CH,C-3),120.2(CH,C- 5),116.3(C,C-12),115.2(C,C-8),115.0(C, C-4),112.7(CH2,C-22),110.4(CH,C-2), 109.0(C,C-9),78.3(CH,C-15),76.2(CH,C-14),72.9 (C,C-16),65.4(CH,C-25),63.8 (CH2,C-19),56.6(CH3,14-OCH3),42.5(CH,C-20),26.5(CH3, C-18),26.5(CH3,C-17),22.3 (CH3,C-23),21.2(CH3,25-COOCH3 ),17.2(CH3,C-24)HRESIMS m/z 535.1935([M+Na]+, C28H32O9Na；calc.535.1939).
Compound 2Yellow amorphous powder；[α]D 20=-120 (c 0.1, CH3OH)；IR (KBr) νmax 3442,2929,2358,1639,1593,1471,1242,1072,894cm–1；1H NMR(CDCl3,600MHz) δ:12.71 (1H, brs, 1-OH), 7.72 (1H, d, J=8.4Hz, H-3), 7.21 (1H, s, H-5), 6.86 (1H, d, J= 8.4Hz, H-2), 5.40 (1H, brs, H-25), 5.13 (1H, d, J=2.4Hz, H-14), 4.94 (3H, d, J=2.4Hz, 25- ), OAc 4.78 (1H, s, Ha-22), 4.56 (1H, s, Hb-22), 4.43 (1H, brd, J=10.8Hz, Ha-19), 4.35 (1H, Dd, J=10.8,2.4 Hz, Hb-19), 3.46 (1H, brs, H-15), 3.29 (1H, s, 14-OCH3),2.95(1H,brs,15- OH),2.72(1H,brs, H-20),2.35(3H,s,H-24),1.84(3H,s,H-23),1.42(3H,s,H-18),1.25 (3H,s,H-17).13C NMR (CDCl3,150MHz)δ:184.2(C,C-13),161.5(C,C-1),152.4(C,C-10), 151.7(C,C-11),149.6(C, C-7),142.5(C,C-21),138.6(C,C-6),135.9(CH,C-3),121.2 (CH,C-8),119.0(C,C-5),116.9(C, C-12),115.5(C,C-4),112.2(CH2,C-22),110.5(CH,C- 2),108.9(C,C-9),78.2(CH,C-15),76.2 (CH,C-14),72.9(C,C-16),65.4(CH2,C-19),63.1 (CH,C-25),56.6(CH3,14-OCH3),44.8(CH, C-20),26.5(CH3,C-17),26.5(CH3,C-18),22.5 (CH3,C-23),17.3(CH3,C-24).HRESIMS m/z 493.1839([M+Na]+,C26H30O9Na； calc.493.1833).
Compound 3Yellow amorphous powder；[α]D 20=-107 (c 0.1, CH3OH)；IR (KBr) νmax 3419,2966,2358,1737,1733,1473,1238,1020,829cm–1；1H NMR(DMSO-d6, 600Hz)δ:12.78 (1H, brs, 1-OH), 7.82 (1H, d, J=8.4Hz, H-3), 7.50 (1H, s, H-5), 6.81 (1H, Brs, H-25), 6.77 (1H, d, J=8.4Hz, H-2), 5.47 (1H, d, J=2.8Hz, H-14), 5.19 (1H, d, J= 5.4Hz, 14-OH), 4.79 (1H, s, Ha-22), 4.61 (1H, s, Hb-22), 4.56 (1H, brd, J=11.4Hz, Ha-19), 4.55 (1H, brs, 16-OH), 4.44 (1H, brd, J=7.2Hz, 14-OCH3), 4.20 (1H, dd, J=11.4,2.4Hz, ), Hb-19 3.27 (1H, brd, J=7.2Hz, H-15), 2.68 (1H, brs, H-20), 2.31 (3H, s, H-24), 1.99 (1H, s,25-OH),1.81(3H,s,H-23),1.28(3H,s, H-18),1.21(3H,s,H-17).13C NMR(DMSO-d6, 150Hz)δ:183.1(C,C-13),169.3(C, 25-COOCH3),159.6(C,C-1),151.4(C,C-10),150.5(C, C-11),149.9(C,C-7),141.8(C,C-21), 137.6(C,C-6),135.8(CH,C-3),122.3(CH,C-4), 120.7(C,C-5),115.5(C,C-12),114.7(C,C-8), 112.6(CH2,C-22),109.2(CH,C-2),108.1 (C,C-9),78.0(CH,C-15),72.7(CH,C-16),65.3(C, C-14),64.8(CH,C-25),63.5(CH2,C- 19),41.7(CH,C-20),27.5(CH3,C-18),26.2(CH3,C-17), 22.1(CH3,C-23),21.0(CH3,25- COOCH3 ),16.9(CH3,C-24).HRESIMS m/z 521.1784([M+Na]+, C27H30O9Na；calc.521.1782).
Compound 4Yellow amorphous powder；[α]D 20=+39 (c 0.1, CH3OH)；IR (KBr) νmax 3421,2964,2356,1726,1718,1475,1236,1016,835cm–1；1H NMR(DMSO-d6, 600Hz)δ:12.84 (1H, brs, 1-OH), 7.83 (1H, d, J=8.4Hz, H-3), 7.40 (1H, s, H-5), 6.78 (1H, d, J=8.4Hz, H-2), 5.81 (1H, brs, H-25), 5.48 (1H, brs, H-14), 5.26 (1H, d, J=3.6Hz, 25-OH), 5.17 (1H, d, J=3.6Hz, 14-OH), 4.74 (1H, s, Ha-22), 4.55 (1H, s, Hb-22), 4.54 (1H, brs, 16- ), OH 4.46 (1H, brs, J=11.4Hz, Ha-19), 4.46 (1H, brd, J=6.6Hz, 15-OH), 4.34 (1H, dd, J= 11.4,2.4Hz, Hb-19), 3.27 (1H, brd, J=6.6Hz, H-15), 2.51 (1H, brs, H-20), 2.29 (3H, s, H- 24),1.78(3H,s,H-23),1.29(3H, s,H-18),1.22(3H,s,H-17).13C NMR(DMSO-d6,150Hz)δ: 183.4(C,C-13),159.6(C,C-1), 151.1(C,C-10),150.5(C,C-11),148.7(C,C-7),142.8(C, C-21),137.2(C,C-6),135.6(CH,C-3), 122.2(CH,C-4),121.0(C,C-8),119.1(C,C-5), 115.8(C,C-12),111.9(CH2,C-22),109.0(CH, C-2),108.1(C,C-9),78.0(CH,C-15),72.7 (CH,C-16),65.2(C,C-14),63.5(CH2,C-19),60.9 (CH,C-25),44.4(CH,C-20),27.5(CH3,C- 18),26.2(CH3,C-17),22.4(CH3,C-23),16.9(CH3, C-24).HRESIMS m/z 457.1857([M+H]+, C25H29O8；calc.457.1857).
Compound 5Yellow amorphous powder；[α]D 20=-92 (c 0.1, CH3OH)；IR (KBr) νmax 3432,2926,2357,1662,1587,1465,1236,1064,847cm–1；1H NMR(CDCl3,600Hz) δ:12.97 (1H, brs, 1-OH), 7.59 (1H, d, J=8.4Hz, H-3), 7.24 (1H, s, H-5), 6.88 (1H, brs, H- 25), 6.77 (1H, d, J=8.4Hz, H-2), 5.41 (1H, d, J=1.8Hz, H-14), 5.00 (1H, d, J=2.4Hz, H- 15), 4.80 (1H, s, Ha-22), 4.74 (1H, s, Hb-22), 4.54 (1H, brd, J=10.8Hz, Ha-19), 4.32 (1H, Dd, J=10.8,3.0Hz, Hb-19), 3.34 (3H, s, 14-OCH3),2.72(1H,brs,H-20),2.36(3H,s,H- 24),2.10(3H,s,25-COOCH3),1.92 (3H,s,15-COOCH3),1.88(3H,s,H-23),1.56(3H,s,H- 18),1.22(3H,s,H-17).13C NMR(CDCl3, 150Hz)δ:183.0(C,C-13),170.2(C,15-COOCH3), 170.1(C,25-COOCH3),162.0(C,C-1), 152.2(C,C-10),151.5(C,C-11),150.3(C,C-7), 141.6(C,C-21),137.6(C,C-6),134.1(C,C-3), 120.3(CH,C-5),116.5(C,C-12),115.1(C, C-8),113.4(C,C-4),112.7(CH2,C-22),110.0(CH, C-2),109.1(C,C-9),77.0(CH,C-15), 76.4(CH,C-14),72.7(C,C-16),65.4(CH,C-25),63.8 (CH2,C-19),57.1(CH3,14-OCH3), 42.5(CH,C-20),27.9(CH3,C-18),26.9(CH3,C-17),22.4 (CH3,C-23),21.3(CH3,25- COOCH3 ),20.5(CH3,15-COOCH3 ),17.3(CH3,C-24).HRESIMS m/z 577.2048([M+Na]+, C30H34O10Na；calc.577.2044).
Compound 6Yellow amorphous powder；[α]D 20=-73 (c 0.1, CH3OH)；IR (KBr) νmax 3434,2929,2354,1665,1587,1466,1232,1069,852cm–1；1H NMR(CDCl3,600Hz) δ:12.74 (1H, brs, 1-OH), 7.65 (1H, d, J=8.4Hz, H-3), 7.22 (1H, s, H-5), 6.82 (1H, d, J= 8.4Hz, H-2), 5.42 (1H, d, J=1.2Hz, H-14), 5.40 (1H, brs, H-25), 5.02 (1H, d, J=2.4Hz, H- 15), 4.86 (1H, d, J=3.0 Hz, 25-OH), 4.78 (1H, s Ha-22), 4.55 (1H, s, Hb-22), 4.43 (1H, brd, J=10.8Hz, Ha-19), 4.36 (1H, dd, J=10.8,3.0Hz, Hb-19), 3.34 (3H, s, 14-OCH3),2.73(1H, brs,H-20),2.37(3H,s,H-24),1.91 (3H,s,15-COOCH3),1.84(3H,s,H-23),1.56(3H,s,H- 18),1.22(3H,s,H-17).13C NMR(CDCl3, 150Hz)δ:184.2(C,C-13),170.2(C,25-COOCH3), 161.8(C,C-1),152.4(C,C-10),151.7(C, C-11),149.7(C,C-7),142.6(C,C-21),138.6(C, C-6),134.6(C,C-3),121.2(CH,C-8),119.1(C, C-5),117.0(C,C-12),113.8(C,C-4), 112.2(CH2,C-22),110.1(CH,C-2),109.0(C,C-25),57.1 (CH3,14-OCH3),44.8(CH,C-20), 27.9(CH3,C-18),26.9(CH3,C-17),22.5(CH3,C-23),20.4 (CH3,15-COOCH3 ),17.4(CH3,C- 24).HRESIMS m/z 535.1939([M+Na]+,C28H32O9Na；cacl. 535.1939).
Compound 7Yellow amorphous powder；[α]D 20=-56 (c 0.1, CH3OH)；IR (KBr) νmax 3446,2972,2368,1733,1645,1471,1249,1029,831cm–1；1H NMR(CDCl3,600Hz) δ:13.00 (1H, brs, 1-OH), 7.73 (1H, d, J=8.4Hz, H-3), 7.24 (1H, s, H-5), 6.90 (1H, brs, H- 25), 6.79 (1H, d, J=8.4Hz, H-2), 5.28 (1H, brs, H-14), 4.85 (1H, s, Ha-22), 4.82 (2H, s, H- 17), 4.77 (1H, s, Hb-22), 4.55 (1H, brd, J=10.8Hz, Ha-19), 4.27 (1H, dd, J=10.8,2.4Hz, ), Hb-19 4.27 (1H, d, J=8.4Hz, H-15) 2.76 (1H, brs, 14-OH), 2.72 (1H, brs, H-20), 2.52 (1H, brs,15-OH),2.35(3H,s,H-24),2.08 (3H,s,25-COOCH3 ),1.89(3H,s,H-23),1.82(3H,s,H- 18).13C NMR(CDCl3,150Hz)δ:183.1 (C,C-13),170.0(C,25-COOCH3),161.7(C,C-1),152.0 (C,C-10),151.6(C,C-11),150.3(C,C-7), 143.4(C,C-16),141.4(C,C-21),137.7(C,C- 6),134.5(CH,C-3),120.2(CH,C-5),117.7(C,C-4), 116.3(C,C-12),115.0(C,C-8),113.7 (CH2,C-17),112.8(CH2,C-22),110.3(CH,C-2),108.2(C, C-9),79.1(CH,C-15),68.8(CH, C-14),65.5(CH,C-25),63.8(CH2,C-19),42.5(CH,C-20),22.4 (CH3,C-23),21.2(CH3,25- COOCH3 ),18.6(CH3,C-18),17.3(CH3,C-24).HRESIMS m/z 503.1667([M+Na]+,C27H28O8Na； calc.503.1676).
Compound 8Yellow amorphous powder；[α]D 20=-113 (c 0.1, CH3OH)；IR (KBr) νmax 3431,2972,2352,1733,1637,1471,1249,1054,817cm–1；1H NMR(CDCl3,600Hz) δ:12.70 (1H, brs, 1-OH), 7.76 (1H, d, J=8.4Hz, H-3), 7.20 (1H, s, H-5), 6.79 (1H, d, J= 8.4Hz, H-2), 5.41 (1H, brs, H-25), 5.28 (1H, brs, H-14), 4.99 (1H, d, J=8.4Hz, 25-OH), 4.83 (1H, s, Ha-22), 4.82 (2H, s, H-17), 4.60 (1H, s, Hb-22), 4.41 (1H, brd, J=10.8Hz, Ha- 19), 4.33 (1H, dd, J=10.8,2.4Hz, Hb-19), 4.26 (1H, d, J=5.4Hz, H-15), 2.94 (1H, brs, 14- ), OH 2.73 (1H, brd, J=2.4Hz, H-20), 2.59 (1H, brs, 15-OH), 2.35 (3H, s, H-24), 1.86 (3H, s, H-23),1.83(3H,s,H-18).13C NMR (CDCl3,150Hz)δ:184.3(C,C-13),161.4(C,C-1),152.1 (C,C-10),151.8(C,C-11),149.8(C, C-7),143.3(C,C-16),142.5(C,C-21),138.7(C,C-6) 135.0(CH,C-3),121.4(C,C-8),118.9(CH, C-5),118.2(C,C-4),116.8(C,C-12),113.7 (CH2,C-17),112.3(C,C-22),110.3(CH,C-2),108.7 (C,C-9),79.1(CH,C-15),68.8(CH,C- 14),64.8(CH2,C-19),63.3(CH,C-25),45.0(CH,C-20), 22.5(CH3,C-23),18.6(CH3,C-18), 17.4(CH3,C-24).HRESIMS m/z 461.1569([M+Na]+, C25H26O7Na；cacl.461.1571).
Embodiment 2
(1) culture of marine fungi ZA-01 strains
Culture medium 10wt% containing glucose, yeast extract 4.0wt%, albumen used in the Spawn incubation of marine fungi ZA-01 Peptone 4.0wt%, agar 6.0wt%, coarse sea salt 10wt%, remaining is water, and test tube slant is made in when use, and fungal bacterial strain is 35 It is cultivated 5 days at DEG C.
(2) fermented and cultured of marine fungi ZA-01
Fermentation medium used in the fermented and cultured of marine fungi ZA-01 is to contain rice in each 1000mL conical flasks 150g、 NaNO3 0.6g、KH2PO4 0.2g、MgSO4·7H2O 0.01g、NaCl 0.1g、FeSO40.05g, sucrose 6g, water 150mL, bacterial strain are cultivated 45 days in 35 DEG C of standing for fermentation, obtain fermentate.
(3) the separation analysis of oxa- anthraquinone analog compound
The fermentate obtained by step (2) is taken, is extracted with ethyl acetate 4 times, combined ethyl acetate extract liquor is concentrated under reduced pressure To coarse extract, normal phase silica gel column chromatography separation, stationary phase are first carried out：100~200 mesh silica gel, mobile phase are 25vol% acetic acid Ethyl ester/petroleum ether mixed solution elutes 3 column volumes, normal phase silica gel column chromatography separation is carried out again after eluent concentration, Gu Determine phase：200~300 mesh silica gel, mobile phase are 75vol% methylene chloride/methanol mixed solvents, elute 3 column volumes.
Reversed-phase silica gel column chromatography separation is carried out after eluent concentration, stationary phase is preferably C18Silica gel, mobile phase are preferably 70vol% methanol/water mixed solutions elute 2 column volumes, Sephadex LH20 gel column chromatographies are carried out after eluent concentration Separation, mobile phase：Dichloromethane elutes 5 column volumes, high performance liquid chromatography separation, stationary phase is carried out after eluent concentration： Half prepares C18Chromatographic column, XBridge OBD, 5 μm, 10 × 250mm, mobile phase is 80vol% methanol/water mixed solutions, and partly Prepare silica gel chromatographic column, ViridisTMSilica 2-Ethylpyridine, 5 μm, 10 × 250mm, mobile phase 85vol% Petroleum ether/alcohol mixed solution, preparative separation obtains compound 1-8, and structural identification data is consistent with embodiment 1.
Other Spawn incubations for not particularly pointed out in Examples 1 and 2, fermentation condition and normal phase silica gel column chromatography separation, Reversed-phase silica gel column chromatography separation, gel column chromatography separation, efficient liquid phase chiral chromatogram separation etc. other experimental operating conditions be The experimental operating conditions of this field routine, those skilled in the art can reasonably be selected according to actual needs.
The antitumor activity of gained oxa- anthraquinone analog compound
(1) antitumor activity is tested
Using MTT methods to human breast cancer cell (MDA-MB-231 and MCF-7), stomach cancer cell (MGC-803), uterine neck The external inhibitory activity of cancer cell (HeLa) and lung epithelial cancer cell (A-549) is tested.
(2) activity test method
By cell growth rate, certain amount is in the cell of exponential phase and is inoculated in 96 with the concentration in 90 holes μ L/ In well culture plate, 10 holes μ L/ of sample to be tested are added in culture afterwards for 24 hours, and to each cell strain, each concentration gradient is done three and put down Row.Cell is in 37 DEG C, 5%CO2Under the conditions of culture 48h after, add MTT (Sigma) liquid 5mg/mL, with physiological saline configure 20 μ L/ Hole；Continue after cultivating 4h, 50 holes μ L/ three liquid (10%SDS-5% isobutanol -0.01mol/L HCl) are added, are placed in CO2Training It supports in case overnight.Then 570 values of OD are surveyed with microplate reader.Adriamycin is as positive control drug.
(3) active testing result
Test result shows, compound 1 can selectivity inhibition lung epithelial cancer cell (A-549) growth, compound 3,6 To human breast cancer cell (MDA-MB-231 and MCF-7), stomach cancer cell (MGC-803), cervical cancer cell (HeLa) and lung epithelial Cancer cell (A-549) all has a strong inhibitory effect, and inhibits the IC of tumor cell line50Value (μM) is shown in Table 1.
Table 1：
The antibacterial activity of gained oxa- anthraquinone analog compound
(1) antibacterial activity is tested
Using gradient dilution method to micrococcus lysodeikticus (Micrococcus lysodeikticus), bacillus anthracis (Bacillus anthraci), Salmonella typhi (Salmonella typhi) and clostridium perfringen (Enterobacter Aerogenes active testing) is carried out.
(2) activity test method
In aseptic superclean bench, takes appropriate bacteria culture liquid medium to be added in blank culture solution and is diluted, Dilution is generally 1:1000 or 1:500.Diluted liquid spawn is taken with sterile liquid-transfering gun (pipette tips pass through sterilization treatment) 198 μ L are added on 96 orifice plates, and the 2 μ L samples to be tested (crude extract or monomer chemical combination of DMSO configurations is added in first hole Object solution), doubling dilution is taken turns doing to the 8th concentration gradient with liquid-transfering gun, and mixing, 37 DEG C of cultures are shaken after dilution 18h -22h measure absorbance with microplate reader (630nm), obtain the minimal inhibitory concentration (MIC) of sample.DMSO's is final dense Degree is maintained at 1%.Each sample concentration sets three Duplicate Samples, in addition sets blank control, negative control (DMSO) and the positive It compares (Ciprofloxacin).
(3) active testing result
Test result shows that compound 1-6 is to micrococcus lysodeikticus (Micrococcus lysodeikticus), anthrax bar Bacterium (Bacillus anthraci), Salmonella typhi (Salmonella typhi) and clostridium perfringen (Enterobacter Aerogenes it is 20.0 μ g/mL) to have weak inhibitory activity, MIC value.Compound 7 and 8 pairs of micrococcus lysodeikticus (Micrococcus lysodeikticus), bacillus anthracis (Bacillus anthraci), Salmonella typhi (Salmonella typhi) and clostridium perfringen (Enterobacter aerogenes) have strong inhibitory activity, compound 7 It is respectively 0.78 μ g/mL, 12.5 μ g/mL, 6.13 μ g/mL and 6.13 μ g/mL, compound 8 to inhibit MIC value to four pathogen strain bacterium It is respectively 6.13 μ g/mL, 12.5 μ g/mL, 6.13 μ g/mL and 6.13 μ g/mL, positive control to inhibit MIC value to four pathogen strain bacterium It is respectively 0.19 μ g/mL, 1.56 μ g/mL, 3.13 μ g/mL and 1.56 μ g/mL that four pathogen strain bacterium of Ciprofloxacin pair, which inhibits MIC value,. Experiment shows the oxa- anthraquinone analog compound containing 4 prenylations and 14,15- dihydroxy of the invention to a variety of pathogens With inhibitory activity, it can be made into antiseptic, be with a wide range of applications.

Claims (10)

1. a kind of marine aspergillus, characterized in that the marine aspergillus is aspergillus（Aspergillussp.）ZA-01 bacterial strains, preservation Date is on January 25th, 2018, and deposit number is CGMCC No.15270, and depositary institution is Chinese microorganism strain preservation management Committee's common micro-organisms center, depositary institution address are Yard 1, BeiChen xi Road, Chaoyang District, Beijing City 3.
2. a kind of marine aspergillus source oxa- anthraquinone analog compound, characterized in that the structural formula of the compound is
Wherein, R independently is OH or OAc.
3. a kind of preparation method of the marine aspergillus source oxa- anthraquinone analog compound described in claim 2, characterized in that including Following steps：
（1）By marine aspergillus described in claim 1（Aspergillussp.）ZA-01 inoculations are in bacterium culture medium Carry out Spawn incubation；
（2）It after the completion of Spawn incubation, is inoculated in fermentation medium and is fermented, obtain fermentate；
（3）Extraction 2-4 times is carried out to fermentate with ethyl acetate, thick leaching is concentrated under reduced pressure to give after combined ethyl acetate extract liquor Cream；
（4）Chromatographic isolation is carried out up to the oxa- anthraquinone analog compound to gained coarse extract, the chromatographic isolation is successively Carry out normal phase silica gel column chromatography separation, reversed-phase silica gel column chromatography separation, gel column chromatography separation and high performance liquid chromatography separation.
4. the preparation method of marine aspergillus source oxa- anthraquinone analog compound according to claim 3, characterized in that step （1）Described in bacterium culture medium be：1.0-10wt% of glucose, 0.1-4.0wt% of yeast extract, 0.2-4.0wt% of peptone, agar 1.0-6.0wt%, 3.0-10wt% of coarse sea salt, remaining is water；Spawn incubation temperature is 15-35 DEG C, and incubation time is 3-10 days.
5. the preparation method of marine aspergillus source oxa- anthraquinone analog compound according to claim 3, characterized in that step （2）The fermentation medium of middle per unit part includes 60-150 g, NaNO of rice3 0.1–0.6 g、KH2PO4 0.05–0.2 g、MgSO4•7H2O 0.02–0.1 g、NaCl 0.02–0.1 g、FeSO4 0.01-0.05 g, 2-6 g of sucrose, water 50-150 mL；Fermentation culture conditions are stationary culture 20-50 days at 15-35 DEG C.
6. the preparation method of marine aspergillus source oxa- anthraquinone analog compound according to claim 3, characterized in that step （4）Described in normal phase silica gel column chromatography be separated into：First use stationary phase for 100 ~ 200 mesh silica gel, mobile phase is 15-25vol% second Acetoacetic ester/petroleum ether mixed solution is eluted, and elution volume is 35 column volumes, is used again after gained eluent is concentrated Stationary phase is 200 ~ 300 mesh silica gel, and mobile phase is that 65-75vol% methylene chloride/methanol mixed solutions are eluted, elution volume For 23 column volumes.
7. the preparation method of marine aspergillus source oxa- anthraquinone analog compound according to claim 3, characterized in that step （4）Described in the stationary phase that uses of reversed-phase silica gel column chromatography separation for C18Silica gel, mobile phase mix for 60-70vol% methanol/waters Solution, elution volume are 23 column volumes.
8. the preparation method of marine aspergillus source oxa- anthraquinone analog compound according to claim 3, characterized in that step （4）Described in gel column chromatography separation stationary phase be sephadex LH-20, mobile phase is dichloromethane, elution volume 3 5 column volumes.
9. the preparation method of marine aspergillus source oxa- anthraquinone analog compound according to claim 3, characterized in that step （4）Described in the chromatographic column that uses in high performance liquid chromatography separation prepare C for half18Chromatographic column, XBridge OBD, 5 μm, 10 × 250 mm, mobile phase are the methanol/water mixed solution of 75-80vol%；Partly prepare silica gel chromatographic column, ViridisTM Silica 2-Ethylpyridine, 5 μm, 10 × 250 mm, mobile phase is 80-85vol% petroleum ethers/alcohol mixed solution.
10. a kind of application of marine aspergillus source oxa- anthraquinone analog compound in preparing antiseptic, characterized in that the antibacterial Agent using described in claim 2 compound or its pharmaceutically acceptable salt as active ingredient.
CN201810623511.7A 2018-06-15 2018-06-15 Marine aspergillus derived oxaanthraquinone compound, preparation method thereof and application thereof in preparation of antibacterial agent Active CN108660082B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810623511.7A CN108660082B (en) 2018-06-15 2018-06-15 Marine aspergillus derived oxaanthraquinone compound, preparation method thereof and application thereof in preparation of antibacterial agent

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810623511.7A CN108660082B (en) 2018-06-15 2018-06-15 Marine aspergillus derived oxaanthraquinone compound, preparation method thereof and application thereof in preparation of antibacterial agent

Publications (2)

Publication Number Publication Date
CN108660082A true CN108660082A (en) 2018-10-16
CN108660082B CN108660082B (en) 2022-04-22

Family

ID=63775839

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810623511.7A Active CN108660082B (en) 2018-06-15 2018-06-15 Marine aspergillus derived oxaanthraquinone compound, preparation method thereof and application thereof in preparation of antibacterial agent

Country Status (1)

Country Link
CN (1) CN108660082B (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109694827A (en) * 2019-01-18 2019-04-30 河北大学 Marine fungi source azaphilones class compound and preparation method thereof and preparing the application in anti-vibrios drug
CN109706086A (en) * 2019-01-18 2019-05-03 河北大学 A kind of marine fungi source azaphilones class compound and its preparation method and application
CN111139185A (en) * 2018-11-06 2020-05-12 广州中医药大学(广州中医药研究院) Aspergillus fungi and application thereof
CN111321083A (en) * 2020-03-27 2020-06-23 河北大学 Marine fungus-derived azaphilones dimer compound and application thereof in antitumor agent
CN114149445A (en) * 2021-11-03 2022-03-08 中南民族大学 Preparation method of xanthone compound and application of xanthone compound in resisting drug-resistant bacteria
CN115466268A (en) * 2022-09-26 2022-12-13 云南大学 Oxa-anthraquinone compound with antibacterial and anti-inflammatory activities, preparation method and application thereof, and pharmaceutical composition

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104911121A (en) * 2015-04-07 2015-09-16 浙江省农业科学院 Aspergillus awamori and its microbe inocula and application thereof
CN107841466A (en) * 2016-09-19 2018-03-27 扬州大学 A kind of method that penicillic acid is prepared by marine Penicillum category fungi on a large scale

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104911121A (en) * 2015-04-07 2015-09-16 浙江省农业科学院 Aspergillus awamori and its microbe inocula and application thereof
CN107841466A (en) * 2016-09-19 2018-03-27 扬州大学 A kind of method that penicillic acid is prepared by marine Penicillum category fungi on a large scale

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
MANGALADOSS FREDIMOSES等，: "New Prenylxanthones from the Deep-Sea Derived Fungus Emericella sp. SCSIO 05240", 《MARINE DRUGS》 *
王碧霞等: "中国东海及东太平洋海山区来源抗菌活性海洋微生物的筛选研究", 《中国海洋药物》 *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111139185A (en) * 2018-11-06 2020-05-12 广州中医药大学(广州中医药研究院) Aspergillus fungi and application thereof
CN111139185B (en) * 2018-11-06 2023-03-10 广州中医药大学(广州中医药研究院) Aspergillus fungi and application thereof
CN109694827A (en) * 2019-01-18 2019-04-30 河北大学 Marine fungi source azaphilones class compound and preparation method thereof and preparing the application in anti-vibrios drug
CN109706086A (en) * 2019-01-18 2019-05-03 河北大学 A kind of marine fungi source azaphilones class compound and its preparation method and application
CN109706086B (en) * 2019-01-18 2022-08-12 河北大学 Marine fungus-derived azaphilones compound as well as preparation method and application thereof
CN109694827B (en) * 2019-01-18 2022-08-12 河北大学 Marine fungus-derived azaphilones compound, preparation method thereof and application thereof in preparation of anti-vibrio drugs
CN111321083A (en) * 2020-03-27 2020-06-23 河北大学 Marine fungus-derived azaphilones dimer compound and application thereof in antitumor agent
CN111321083B (en) * 2020-03-27 2023-05-16 河北大学 Ocean fungus source azaphilines dimer compound and application thereof in antitumor agent
CN114149445A (en) * 2021-11-03 2022-03-08 中南民族大学 Preparation method of xanthone compound and application of xanthone compound in resisting drug-resistant bacteria
CN114149445B (en) * 2021-11-03 2023-02-14 中南民族大学 Preparation method of xanthone compound and application of xanthone compound in resisting drug-resistant bacteria
CN115466268A (en) * 2022-09-26 2022-12-13 云南大学 Oxa-anthraquinone compound with antibacterial and anti-inflammatory activities, preparation method and application thereof, and pharmaceutical composition
CN115466268B (en) * 2022-09-26 2023-05-16 云南大学 Oxaanthraquinone compound with antibacterial and anti-inflammatory activity, preparation method and application thereof, and pharmaceutical composition

Also Published As

Publication number Publication date
CN108660082B (en) 2022-04-22

Similar Documents

Publication Publication Date Title
CN108660082A (en) A kind of marine aspergillus source oxa- anthraquinone analog compound and preparation method thereof and the application in preparing antiseptic
CN108753627A (en) A kind of marine aspergillus source oxa- anthraquinone analog compound and preparation method thereof and the application in preparing antitumor agent
CN107298671A (en) Come from the secalonic acid H of penicillium oxalicum and prepare the application of anti-human colon cancer drug
CN101974464B (en) Streptomyces and process for preparing antimycin antibiotics by fermentation using same
CN107721990A (en) The iso-indole ketone compounds in a kind of marine fungi source and preparation method thereof and the application in anti-inflammatory drug is prepared
CN109694827A (en) Marine fungi source azaphilones class compound and preparation method thereof and preparing the application in anti-vibrios drug
CN109706086A (en) A kind of marine fungi source azaphilones class compound and its preparation method and application
CN107298672A (en) The secalonic acid I for coming from penicillium oxalicum is preparing the application of anti-human colon cancer drug
CN113481106A (en) Deep sea source penicillium mycoides and obtained compound
CN110863021B (en) Preparation method and application of cytochalasin compound
CN102030791A (en) Four tiacumicin compounds as well as preparation methods and applications thereof in preparing antimicrobial agents
CN106432168B (en) The anti-vibrios reactive compound and preparation method thereof in mangrove cusp sea lotus endogenetic fungus source
CN104876945B (en) A kind of alkaloid dimer and preparation method thereof and the application as antivirotic
CN111411045B (en) Marine fungus-derived azaphilones dimer compound and preparation method thereof
CN109134574A (en) Steroidal compounds and the preparation method and application thereof and anti-tumor drug
CN105441504B (en) A kind of preparation method of CYCLIC DIPEPTIDES compounds
CN1928075B (en) Strain capable of generating avermectin B component and utilization thereof
CN103145740B (en) Sulfoxide alkaloid compound as well as preparation method and application for same
CN109112171A (en) A kind of preparation method of the antibacterial substance based on marine microorganism
CN106047751B (en) Separation method and the application of one plant of quasi- promise Cattell actinomyces and its active metabolite
CN115109023A (en) Macrolide compound FWYZ52-A, and fermentation strain, fermentation method and application thereof
CN106432169B (en) A kind of active isocoumarin class compound of anti-vibrios and its crystal
CN109234175A (en) The Fusarium oxysporum DCLZJ-4 bacterial strain and application thereof of one plant of production chonglou saponin
CN102168020B (en) Marine-source fungus and application thereof
CN108727169A (en) A kind of preparation method of the biphenyl ether compound in marine fungi source and the application as antiseptic

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant