CN108739810A - Application of the anthraquinone analog compound as bioflm inhibiting agents - Google Patents

Application of the anthraquinone analog compound as bioflm inhibiting agents Download PDF

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CN108739810A
CN108739810A CN201810586217.3A CN201810586217A CN108739810A CN 108739810 A CN108739810 A CN 108739810A CN 201810586217 A CN201810586217 A CN 201810586217A CN 108739810 A CN108739810 A CN 108739810A
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analog compound
anthraquinone analog
application
inhibiting agents
bioflm inhibiting
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徐颖
张煜
宋芝蔓
尹琦
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Shenzhen University
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Shenzhen University
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Abstract

The invention belongs to technological field of biochemistry, and in particular to a kind of application of anthraquinone analog compound as bioflm inhibiting agents, in the general structure such as specification of the anthraquinone analog compound shown in Formulas I：Wherein, R1、R2、R3、R4、R5、R6、R7And R8It is respectively and independently selected from hydrogen-based, hydroxyl, methyl, methylol and at least one of with carboxyl.Such anthraquinone analog compound can inhibit the growth of biomembrane, and there can be solution film activity completely to ripe biomembrane, therefore, the anthraquinone analog compound can be used as the antibiont film drug used in clinic as bioflm inhibiting agents, and the antibiont film of medical embedded equipment and artificial organs infects coating material, and marine antifoulant etc., there is good application prospect.

Description

Application of the anthraquinone analog compound as bioflm inhibiting agents
Technical field
The invention belongs to technological field of biochemistry, and in particular to a kind of anthraquinone analog compound is as bioflm inhibiting agents Using.
Background technology
Bacterial biof iotalm (Bacterial Biofilm) is wrapped in certainly by the bacterial cell for being attached to various solid object surfaces The structural bacterial flora kind that aqueous polymerization matrix secreted by body is formed.99% microorganism is with biofilm states in nature For main life style.Clinically, be more than 80% infection it is related with pathogen biomembrane, biomembrane infection be that bacterial drug is resistance to By the main cause with infection recurrent exerbation.Biomembrane once being formed, the raising that bacterial drug resistance will be hundreds and thousands of times.In 2017 State bacterial drug resistance monitoring (CHINET) is a variety of main the results show that the drug resistance of clinical the main pathogenic fungi rises continuously and healthily The drug resistance of pathogen is up to 70%-100%.The global number for dying of the infection of drug-resistant bacteria biomembrane every year is about 700,000, is arrived The year two thousand fifty will be more than 10,000,000, Asia or more than 5,000,000.The U.S. is used to treat the expense of drug-resistant bacteria biomembrane infection every year Up to hundreds of hundred million dollars.Meanwhile the speed of the remote superman's kind new medicine exploitation of acquisition speed of bacterial drug resistance, if do not checked, the mankind " rear antibiotic epoch " will be entered, and return to the Dark Ages helpless to bacterium infection before antibiotic is found.
It is bacterial drug resistance and the main cause of infection based on biomembrane, inhibition/releasing biomembrane can release the drug of bacterium Barrier reduces the dosage of cured by antibiotics infection, to contain the further deterioration of bacterial drug resistance, therefore, novel antibiont The research and development of film preparation are of great significance to clinical treatment.However, in the past 20 years, the selection result of antibiont film activity substance is not Fully up to expectations, the low bio-toxicity of Clinical practice, high biofilm inhibitor activity, effect bacterium wide spectrum can be put by present lacking Monomer medicine.Antibiotic or derivatives thereof, analog and antibacterial peptide etc. are mainly pressed down by killing bacterium reduction biomass Biofilm formation processed, membrane removal concentration are typically 100-1000 times of its bacteriocidal concentration, do not break away from the quick of bacterial drug resistance still It generates.Therefore, safely, effectively, side effect it is low broad-spectrum biological film inhibitor it is still more rare.
On the other hand, marine biofouling refers to that marine animal, plant and microorganism attachment are accumulated in and impregnated by seawater Stromal surface, thus the phenomenon that bringing adverse effect to human production activity and the marine eco-environment.At present in the world there are about 4000 kinds of marine fouling organisms, about 200 kinds of the main fouling organism of China coast, what wherein harmfulness was larger have barnacle, bryozoan, Pipe worm and shellfish etc..The harm of marime fouling mainly has：The roughness and weight for increasing hull, to increase ship resistance and combustion Oil consumption makes overall navigation cost be increased up to 70%；Seawater cooling cycle pipeline is blocked, the corrosion of attachment base material is accelerated；It strives Take the shellfish of cultivation, the attachment base of algae and bait by force, blocking mesh influences aquaculture yield and quality etc..It is estimated that marime fouling It transports by sea caused by annual and the loss of other marine industries is more than 6,500,000,000 dollars.In recent years, the Forming Mechanism of marime fouling is studied The result shows that：It is being stained the starting stage, marime fouling microorganism is initially formed biomembrane, referred to as " miniature to be stained ", is that other are big The attachment of type fouling organism provides favourable conditions, is the important stage that marime fouling is formed.Prevent marine biofouling most at present Common method is to apply the antifouling paint coat containing anti-fouling agent, and widely used anti-fouling agent is to marine eco-environment destructiveness pole Greatly, therefore the anti-fouling agent of exploitation efficient and environment-friendly type is urgently to be resolved hurrily.
Marine microorganism has the characteristics that in high volume to ferment, does not depend on natural resources, is environmental-friendly, simultaneously because raw Border is unique, and Structures of Natural Products is novel, activity is extensive, is always the important sources of drug development.Have at present many from sea The antibiont film activity substance of foreign microbial natural products is reported, although screening also rests on the blending ingredients stage, has been filled Divide the bioflm inhibiting agents screening for showing marine microorganism brilliance and potentiality to be exploited.Meanwhile many fouling resistances efficiently, less toxic Reactive compound is isolated from the marine organisms such as sponge, coral and seaweed and its symbiotic and epiphyte microorganism, shows the micro- life in ocean Object is also important the potential resource of novel antifouling agent exploitation.
Invention content
It is an object of the invention to overcome the above-mentioned deficiency of the prior art, a kind of anthraquinone analog compound is provided as biomembrane The application of inhibitor, it is intended to solve existing biofilms inhibitor and lack safe efficient, broad-spectrum biological film inhibitor technology to ask Topic.
For achieving the above object, the technical solution adopted by the present invention is as follows：
One aspect of the present invention provides a kind of application of anthraquinone analog compound as bioflm inhibiting agents, the Anthraquinones chemical combination The general structure of object is as shown in following formula I：
Wherein, R1、R2、R3、R4、R5、R6、R7And R8At least one be respectively and independently selected from hydrogen-based, hydroxyl, methyl and carboxyl Kind.
Anthraquinone analog compound provided by the invention shows stronger antibiont film activity as bioflm inhibiting agents, leads to Overtesting proves that such anthraquinone analog compound can inhibit the growth of biomembrane, and can have solution completely to ripe biomembrane Film activity, therefore, the anthraquinone analog compound can be used as the antibiont film drug used in clinic, and doctor as bioflm inhibiting agents Coating material and marine antifoulant etc. are infected with the antibiont film of implantation equipment and artificial organs, before there is application well Scape.
Description of the drawings
Fig. 1 is the negative ion mode LC-MS spectrograms of anthraquinone analog compound Formula V in the embodiment of the present invention 1；
Fig. 2 is the negative ion mode LC-MS spectrograms of anthraquinone analog compound Formula IV in the embodiment of the present invention 1
Fig. 3 is the solution film activity violet staining figure of anthraquinone analog compound in the embodiment of the present invention 2.
Specific implementation mode
In order to make technical problems, technical solutions and advantageous effects to be solved by the present invention be more clearly understood, below in conjunction with Embodiment, the present invention will be described in further detail.It should be appreciated that specific embodiment described herein is only used to explain The present invention is not intended to limit the present invention.
A kind of application an embodiment of the present invention provides anthraquinone analog compound as bioflm inhibiting agents, the Anthraquinones The general structure of object is closed as shown in following formula I：
Wherein, R1、R2、R3、R4、R5、R6、R7And R8At least one be respectively and independently selected from hydrogen-based, hydroxyl, methyl and carboxyl Kind.
Anthraquinone analog compound provided in an embodiment of the present invention shows stronger antibiont film and lives as bioflm inhibiting agents Property, it is proved by testing, such anthraquinone analog compound can inhibit the growth of biomembrane, and can have to ripe biomembrane Complete solution film activity, therefore, the anthraquinone analog compound can be used as the antibiont film drug used in clinic as bioflm inhibiting agents, with And the antibiont film of medical embedded equipment and artificial organs infects coating material and marine antifoulant etc., has and answers well Use foreground.
Further, in the application of the embodiment of the present invention, in general structure shown in the Formulas I, R2、R3、R6And R7Respectively It is independently selected from least one of hydrogen-based, hydroxyl, methylol and carboxyl.Or R1、R4、R5And R8It is respectively and independently selected from hydrogen-based, hydroxyl At least one of with methyl.It is highly preferred that the anthraquinone analog compound is any of following Chinese style II- Formula VII：
Further, in the application of the embodiment of the present invention, antibiosis of the anthraquinone analog compound as bioflm inhibiting agents A concentration of 25-100 μ g/mL of object film activity.The anthraquinone analog compound as shown in above-mentioned Formula II-VII, for having released pathogen The biomembrane of formation：Formula III, formula IV, Formula V respectively 100 μ g/mL, 100 μ g/mL, 25 μ g/mL concentration under can solve film completely； Formula IV has apparent solution film activity in 50 μ g/mL.
Preferably, the anthraquinone analog compound is methicillin-resistant staphylococcus aureus resistance as bioflm inhibiting agents Bioflm inhibiting agents, can biofilm for 24 hours established to methicillin-resistant staphylococcus aureus have completely solution film Activity has the purposes to methicillin-resistant staphylococcus aureus resistance biomembrane.Because of the antibiont film of the anthraquinone analog compound Activity can be used to prepare antibiont film as bioflm inhibiting agents as the medicament sources for preventing/releasing pathogen biomembrane The antibiont film of drug, medical embedded equipment and/or artificial organs infects coating material.
Preferably, the anthraquinone analog compound is used to prepare marine antifoulant as bioflm inhibiting agents.The ocean is anti- The minimum concentration of the anti-fouling activity of dirty agent is 12.5 μ g/mL.The anthraquinone analog compound as shown in Formula IV has good anti-pollution Damage activity can completely inhibit the attachment of fouling organism bryozoan in final concentration of 12.5 μ g/mL, and to the toxicity of bryozoan larva It is very low, it can be used as the exploitation raw material of marine antifoulant.
Further, in the application of the embodiment of the present invention, metabolite of the anthraquinone analog compound from marine actinomycete Middle extraction obtains.Marine actinomycete is extracted with ethyl acetate in SGTYP cultures as Formula IV and Formula VII compound represented are present in In the metabolite coarse extract that base ferments 4 days.Medium component is sea salt 17g/L, glucose 5g/L, starch 5g/L, yeast extract 1g/L, tryptone 1g/L, peptone 1g/L.Medicinal extract is dissolved as 25mg/mL with dimethyl sulfoxide (DMSO) (DMSO) and uses.Preferably, Marine actinomycete is Streptomyces albolongus strain M54, is detached and is obtained by the present inventor team.Such anthracene Quinones can not depend on natural environment and carry out high-volume fermentation, resourceful, environmental-friendly.
In the embodiment of the present invention, less toxic, nontoxic, efficient, wide spectrum biomembrane is obtained from marine microorganism natural products Inhibitor, to solve the bacterial drug resistance and refractory more infection etc. medical treatment harm that biomembrane is brought；Simultaneously to inhibit marime fouling The starting stage of formation is the formation stages for being stained microbial film, to prevent the formation of marime fouling.In the embodiment of the present invention Anthraquinone analog compound Formulas I-VII is naturally occurring organic compound, and be non-toxic compound, heavy metal free toxicity, It, will not be to ocean ring while fighting marime fouling to will not cause damages to normal cell while anti-microbial pathogen biomembrane Border pollutes.
The present invention successively carried out test of many times, and it is further detailed to invention progress as reference now to lift A partial experiment result Thin description, is described in detail with reference to specific embodiment.
The preparation of 1 anthraquinone analog compound of embodiment
1. fermentation extraction
The Streptomyces albolongus strain M54 single bacteriums grown on picking MA tablets are dropped down onto containing 10mL In the 50mL centrifuge tubes of SGTYP culture mediums, 28 DEG C of 200rpm shake training and obtain seed liquor for 24 hours；By 3mL seed liquors be inoculated in 80mL without In bacterium SGTYP fluid nutrient mediums, 28 DEG C of 200rpm shake training 4 days；It is produced with the metabolism in the ethyl acetate extractive fermentation liquid of 3 times of volumes Object, repetition are extracted twice；Water phase is removed, ethyl acetate phase is evaporated at 40 DEG C with Rotary Evaporators；By the extraction in revolving bottle It takes the chemical reagent such as object methanol, acetone repeatedly to dissolve and be transferred in the centrifuge tube of known weight on a small quantity, is then placed on It weighs after being evaporated in concentrating instrument, the weight of record gained ethyl acetate coarse extract.Coarse extract is dissolved into 25mg/mL with DMSO, It is used in combination ultra performance liquid chromatography-mass spectrometry (UPLC-MS) technology to carry out Information in Mass Spectra acquisition.
2. prepared by separation
2.1 reversed phase column chromatography
Reverse phase silica gel ODS fillers are swollen in methyl alcohol, then are used homogenate wet method loaded in chromatographic column, pressurization is pressed Tightly.Coarse extract air-dry after loaded on above column, with the methanol/waters of different gradients (10%, 15%, 20%, 25%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%；12 set of segmentation successively) mobile phase is done, each gradient eluent volume is 2 A column volume, pressurization with constant flow velocity flow through chromatographic column, collect eluent with 250mL indigo plant mouth bottles, after every bottle of mixing, pipette 200 μ L are detected with high performance liquid chromatography (HPLC), and similar compositions are merged revolving and are collected in test tube.As a result Formula IV and formula VII compounds represented are present in the component of Fr.7 (the 7th set of segmentation of i.e. above-mentioned methanol/water=50%).
2.2 sephadex column chromatographies
Sephadex (Sephadex LH-20) is swollen in methyl alcohol, homogenate wet method is then used to be loaded on gel In column, pressurization compresses.Drop to above column after 2~3cm after eluent, it is with suction pipe that the coarse extract concentrated solution fully dissolved is careful Equably it is added to gel column upper layer.Eluent is methanol and dichloromethane 1:1 mixed solvent, it is slow with the speed of 5sec/ drops Slow elution separation, a pipe is collected per 30min, finally obtains Fr.7-1~50.
It is prepared by 2.3 preparative high performance liquid chromatography instrument
Using acetonitrile as mobile phase A, water is Mobile phase B, is arranged with 1525 analytic type high performance liquid chromatographs of Waters different Service condition makes sample pass through Kinetex 5u PFP 10CA columns (250mm × 4.6mm) to reach target compound and other The effect of compound separation.Then 2489 preparative high performance liquid chromatography instrument of Waters, with the flow velocity of 20mL/min, 40% are used Isocratic method makes the sample F after merging r.7-25 be prepared by Kinetex 5u PFP 100A columns (250mm × 21.2mm). It is unimodal that compound is prepared on preparative high performance liquid chromatography instrument, with analytic type high performance liquid chromatograph point after revolving is dry Analysis.
2.4 nuclear-magnetisms are identified
Obtained compound purity, which is analyzed, with 1525 analytic type liquid chromatographs of Waters reaches 90% or more, and compound Total amount reach 3mg or more, you can compound is dissolved in deuterated DMSO, carry out1HNMR and13CNMR nuclear magnetic resonance figures spectrum analysis, With the structure of authenticating compound.
The data of the structure elucidation of compound are as follows：
Formula IV compound represented：Red brown solid；Molecular formula is C16H10O6；ESI-MS m/z:297[M-H]-(see figure 1)；Spectral data：1H NMR(DMSO-d6, 600MHz) and δ:12.90(1H,s,8-OH),7.72(1H,t,H-6),7.64(1H,d, H-5),7.58(1H,s,H-4),7.34(1H,d,H-7),2.71(3H,s,ArCH3)；13C NMR(DMSO-d6,150MHz)δ: 189.8(C,C-9),182.6(C,C-10),168.7(C,C-12),161.9(C,C-3),141.6(C,C-1),136.8(C,C- 5a),136.5(CH,C-6),133.0(C,C-10a),131.3(C,C-9a),124.9(CH,C-7),122.7(C,C-2), 118.8(CH,C-5),117.4(C,C-8a),112.8(CH,C-4),20.4(CH3,C-11).In nuclear magnetic data and existing literature Data it is almost the same, it is thus determined that the compound be 3,8-Dihydroxy-l-methylanthr-achinon-2- carboxylic acid。
Formula VII compound represented：Red brown solid；Molecular formula is C16H10O7；ESI-MS m/z:313 [M-H] are (see figure 2).Formula IV1HNMR data and Formula V are closely similar, and a peak t has been lacked on 6, compare formula by the molecular weight of Formula IV known to mass spectrum V more 16, only exists the difference of 6-OH.Spectral data：1H NMR(DMSO-d6, 600MHz) and δ:13.14(1H,s,8-OH),11.11 (1H,s,H-4),7.58(1H,brs,6-OH),7.07(1H,d,H-5),6.60(1H,d,H-7),2.68(3H,s,ArCH3)。 Nuclear magnetic data and the data in existing literature are almost the same, it is thus determined that the compound is 3,8-dihydroxy-6-methoxy- 1-methylanthraquinone-2-carboxylic acid。
2 bioactivity of embodiment detects
1 minimum inhibitory concentration (Minimum Inhibition Concentration, MIC) measures
The activation of -80 DEG C of methicillin-resistant staphylococcus aureus (MRSA ATCC43300) is to LB plating mediums, 37 DEG C Culture is for 24 hours；Monoclonal colonies are inoculated into LB liquid medium, 37 DEG C of 200rpm shake training overnight；The 200 times of dilutions of LB culture mediums Cultivation liquid is shaken overnight, and it is 10 to make bacterial concentration5CFU/mL；It takes in 100 μ L dilution bacterium solutions to 96 orifice plates, while 10 μ L concentration is added For the compound of 20,10,5,2.5,1.25,0.625,0.3125mg/mL, 37 DEG C are cultivated 12h and observed afterwards as a result, ultraviolet for 24 hours Spectrophotometer carries out OD595Detection.
Minimum inhibitory concentration (MIC) result is shown：The MIC value of Formula II, VI, VII is all higher than 200 μ g/mL；The MIC of formula III Value is between 6.25-12.5 μ g/mL；The MIC value of formula IV is between 6.25-12.5 μ g/mL；The MIC value of Formula V between Between 12.5-25 μ g/mL.Formula III, IV, V difference lies in the substituent group of the right phenyl ring and replace site different from Formula IV, card Bright bacteriostatic activity site and R6、R7And R8Substitution it is related.
2 biomembrane solution film activities measure
Film formation step：- 80 DEG C of MRSA are activated to LB plating mediums, and 37 DEG C of cultures are for 24 hours；Monoclonal colonies are inoculated into LB In fluid nutrient medium, 37 DEG C of 200rpm are incubated overnight；The LB culture mediums 40 added with 0.5% (w/v) glucose are diluted overnight again Cultivation liquid is shaken, it is 10 to make bacterial concentration5CFU/mL；1mL is added to dilute in bacterium solution to 24 orifice plates, 37 DEG C of stationary cultures are for 24 hours.
Measuring：The LB culture mediums of 0.5% (w/v) glucose addition are added after 24 orifice plate supernatants are outwelled, add simultaneously Enter Formula II-Formula VII compound of 2 μ L difference gradient concentrations, 2 μ L DMSO are added in control group, and 37 DEG C of stationary cultures are for 24 hours；Then it goes Except culture medium, 37 DEG C of dry 30min；1min is fixed with 70% ethyl alcohol, is washed twice with 1 × PBS afterwards；With 1mL 0.5% (w/v) Violet staining 10min；Flowing water cleans uncolored dye liquor, after the dissolving completely of drying at room temperature 10min, 1mL 3% (v/v) sodium acetate Carry out OD595Detection.
Antibiont film activity result：Formula III, Formula V can solve film completely in 100 μ g/mL；Formula IV has bright in 25 μ g/mL Aobvious solution film activity；Formula IV has apparent solution film activity (see the solution biomembrane activity of Fig. 3 anthraquinone analog compounds in 50 μ g/mL Violet staining figure).The causing of the solution film activity difference of Formula IV and Formula VII is R3Whether position has hydroxyl, the R of Formula VII3Do not have Hydroxyl solution film activity is weak, shows this for solution film activity critical sites.
3 anti-fouling activities measure
Experiment material：It is soft to be stained model organism bryozoan Bneritina adults, pick up from Hong Kong banyan Australia (22 ° of 24 ' N/ 114 ° of 21 ' E) fishing row and buoyant raft.The acquisition of bryozoan larva：At room temperature, bryozoan adult is placed on equipped with flowing seawater Sink in, be passed through air in right amount.Then, take appropriate bryozoan adult as in the glass jar for filling fresh filtering sea, light According to young release is begun with after 20-30min, the larva being collected into is used for active testing as early as possible.
Measuring：Several bryozoan larvas are put into 24 orifice plates for filling the fresh filtering seas of 1mL, it is dense that 1 μ L are added Degree is the Formula IV of 25mg/mL and 12.5mg/mL.The DMSO of 0.1% (v/v) is added in negative control group；Positive controls are added not With the Sea-Nine 211 of concentrationTM(anti-fouling agent).24 orifice plates are put under dark condition, after 28 DEG C are placed 3-4h, by 24 orifice plates It is placed on optical body formula microscopically observation, analyzes larva attachment state, records the number of dead larvae and travelling, attachment.
Anti-fouling activity result：Formula IV anti-fouling activity measurement result is shown in Table 1, and (the anti-bryozoan of Formula IV is stained active knot Fruit).After 4h, all adhere to without bryozoan in two holes of final concentration of 25 μ g/mL, and moss borer population of surviving is 19 and 20；It is dense eventually All adhere to without bryozoan in two holes that degree is 12.5 μ g/mL, and moss borer population of surviving is 19 and 18.Due to every bryozoan Physiological status is different, and 1 dead bryozoan can regard incident as in the hole of 25 μ g/mL, can not illustrate it is chemical combination Caused by object, so Formula IV is attached with high inhibition power to bryozoan, and meanwhile it is very low to the toxicity of bryozoan larva.
Table 1
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention All any modification, equivalent and improvement etc., should all be included in the protection scope of the present invention made by within refreshing and principle.

Claims (10)

1. a kind of application of anthraquinone analog compound as bioflm inhibiting agents, the general structure such as following formula of the anthraquinone analog compound Shown in I：
Wherein, R1、R2、R3、R4、R5、R6、R7And R8It is respectively and independently selected from hydrogen-based, hydroxyl, methyl, methylol and carboxyl at least It is a kind of.
2. application as described in claim 1, which is characterized in that in general structure shown in the Formulas I, R2、R3、R6And R7Respectively It is independently selected from least one of hydrogen-based, hydroxyl, methylol and carboxyl.
3. application as described in claim 1, which is characterized in that in general structure shown in the Formulas I, R1、R4、R5And R8Respectively It is independently selected from least one of hydrogen-based, hydroxyl and methyl.
4. application as described in claim 1, which is characterized in that the anthraquinone analog compound is
In it is any.
5. application as described in claim 1, which is characterized in that antibiosis of the anthraquinone analog compound as bioflm inhibiting agents A concentration of 25-100 μ g/mL of object film activity.
6. application as described in claim 1, which is characterized in that the anthraquinone analog compound is anti-resistance to as bioflm inhibiting agents The bioflm inhibiting agents of methicillin staphylococcus aureus.
7. application as described in claim 1, which is characterized in that the anthraquinone analog compound is as bioflm inhibiting agents for making The antibiont film of standby antibiont film drug, medical embedded equipment and/or artificial organs infects coating material.
8. application as described in claim 1, which is characterized in that the anthraquinone analog compound is as bioflm inhibiting agents for making Standby marine antifoulant.
9. application as claimed in claim 8, which is characterized in that the minimum concentration of the anti-fouling activity of the marine antifoulant is 12.5μg/mL。
10. such as claim 1-9 any one of them applications, which is characterized in that the anthraquinone analog compound is from marine actinomycete Metabolite in extract and obtain.
CN201810586217.3A 2018-06-06 2018-06-06 Application of the anthraquinone analog compound as bioflm inhibiting agents Pending CN108739810A (en)

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CN111956636A (en) * 2020-08-21 2020-11-20 中国药科大学 Application of 2-substituted anthraquinone derivative in preparation of medicines for treating candida albicans infection

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CN101274885A (en) * 2007-03-30 2008-10-01 国家海洋局第一海洋研究所 Anthraquinone coumpound for inhibitating plant pathogenic fungi

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Publication number Priority date Publication date Assignee Title
CN111956636A (en) * 2020-08-21 2020-11-20 中国药科大学 Application of 2-substituted anthraquinone derivative in preparation of medicines for treating candida albicans infection
CN111956636B (en) * 2020-08-21 2022-03-18 中国药科大学 Application of 2-substituted anthraquinone derivative in preparation of medicines for treating candida albicans infection

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