CN110063948A - P-hydroxyphenylethanol is used to prepare the purposes for inhibiting the drug of bacterial community induction - Google Patents

P-hydroxyphenylethanol is used to prepare the purposes for inhibiting the drug of bacterial community induction Download PDF

Info

Publication number
CN110063948A
CN110063948A CN201910398611.9A CN201910398611A CN110063948A CN 110063948 A CN110063948 A CN 110063948A CN 201910398611 A CN201910398611 A CN 201910398611A CN 110063948 A CN110063948 A CN 110063948A
Authority
CN
China
Prior art keywords
hydroxyphenylethanol
drug
inhibiting
prodrug
purposes according
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.)
Pending
Application number
CN201910398611.9A
Other languages
Chinese (zh)
Inventor
朱虎
常爱平
王颖璐
陈雯丹
何侨妹
李丽
鱼晓丹
戴晓芸
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.)
Fujian Normal University
Original Assignee
Fujian Normal 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 Fujian Normal University filed Critical Fujian Normal University
Priority to CN201910398611.9A priority Critical patent/CN110063948A/en
Publication of CN110063948A publication Critical patent/CN110063948A/en
Pending legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/045Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05Phenols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents

Abstract

The purposes for inhibiting the drug of bacterial community induction is used to prepare the invention discloses p-hydroxyphenylethanol or its prodrug, the p-hydroxyphenylethanol has the structure as shown in formula (I):

Description

P-hydroxyphenylethanol is used to prepare the purposes for inhibiting the drug of bacterial community induction
Technical field
The present invention relates to the purposes of p-hydroxyphenylethanol or its prodrug, especially p-hydroxyphenylethanols or its prodrug for making The purposes of the standby drug for inhibiting bacterial community induction.
Background technique
Currently, antibiotic is all to realize anti-infectious purpose by directly killing microorganism or suppressing growth of microorganism, Under this survival pressure, bacterium is by changing self mechanism, it is easy to generate drug resistance, this that is to say, it is bright with traditional target spot and The antibacterials that screening technique obtains can not fundamentally solve the problems, such as that drug-resistant bacteria infects.
In recent years, bacterial community induction (Quorum Sensing, QS) system can regulate and control the existence of bacterium with it is pathogenic, Cause the close attention of pharmacy man, it has also become the important target of pharmacy circle development of new antibacterials.Incuded with bacterial community System is the antibacterials of target sieving, entirely different with the mechanism of action of conventional antibiotic, it does not kill bacterium or inhibits single The growth of a bacterium, only inhibits the pathogenic behavior of bacterial community induction regulation, including reduces bacteriotoxin yield, inhibits biological quilt Film is formed, hinder bacteria motility and adjust its excretory system etc., so that it be made to lose pathogenecity, it is prominent to be not easy inducible resistance Become, is accordingly regarded as the novel antibacterial drug of future ideality.
P-hydroxyphenylethanol also known as 4- hydroxylphenylethyl alcohol, popular name tyrosol (Tyrosol) are mainly used as the conjunction such as medicine, fragrance At intermediate, such as synthesis cardiovascular drug Metoprolol, times its element Luo Er etc..
CN106083533B, which discloses 4- hydroxylphenylethyl alcohol, can effectively inhibit the hatching of root-knot nematode egg, to root knot line Egg hatch inhibiting rate is up to 95%.
CN1720802 discloses a kind of biological sprout inhibitor and its application, which is naturally to hydroxyl Base benzyl carbinol and two kinds of benzyl carbinol.Tobacco, flower can be improved as tobacco, vegetables and flowers Suckering agents application in the biological sprout inhibitor The yield of grass and vegetables, improving quality, sprout inhibition effective percentage are average up to 93% or more.
CN1685817 discloses a kind of tobacco and vegetable sprouting inhibitor, belongs to agricultural Suckering agents.The Suckering agents by benzyl carbinol, Or the mixture of p-hydroxyphenylethanol or benzyl carbinol and p-hydroxyphenylethanol, it is dissolved in water and is prepared.The Suckering agents are as tobacco And vegetable sprouting inhibitor application, the yield of tobacco and vegetables, improving quality, sprout inhibition effective percentage average reachable 90% or more can be improved.
Up to the present, there is not yet someone reports p-hydroxyphenylethanol in terms of the drug that preparation inhibits bacterial community induction Application.
Summary of the invention
In view of this, the purpose of the present invention is to provide a kind of p-hydroxyphenylethanol or the new medical usages of its prodrug. The present invention adopts the following technical scheme that realization above-mentioned purpose.
The present invention provides a kind of p-hydroxyphenylethanol or its prodrug is used to prepare the use for inhibiting the drug of bacterial community induction On the way, the p-hydroxyphenylethanol has the structure as shown in formula (I):
In accordance with the purpose of the invention, it is preferable that the drug forms the pharmaceutical preparation for inhibiting bacterial community induction;The medicine Object preparation includes the p-hydroxyphenylethanol or its prodrug, also includes pharmaceutically acceptable auxiliary material.
In accordance with the purpose of the invention, it is preferable that the drug is lived using the p-hydroxyphenylethanol or its prodrug as unique Property ingredient.
In accordance with the purpose of the invention, it is preferable that the drug is formed for inhibiting the bacterial community of chromabacterium biolaceum to incude Pharmaceutical preparation.
In accordance with the purpose of the invention, it is preferable that the drug forms the production for inhibiting the violacein of chromabacterium biolaceum Measure but do not influence the pharmaceutical preparation of the normal growth of chromabacterium biolaceum.
In accordance with the purpose of the invention, it is preferable that the drug is formed for inhibiting the bacterial community of Pseudomonas aeruginosa to incude Pharmaceutical preparation.
In accordance with the purpose of the invention, it is preferable that the drug forms pyo, elastic egg for inhibiting Pseudomonas aeruginosa The yield of white enzyme and proteolytic enzyme but do not influence Pseudomonas aeruginosa normal growth pharmaceutical preparation.
In accordance with the purpose of the invention, it is preferable that the drug forms the pharmaceutical preparation for inhibiting bacterial community induction;Unit medicine The content of p-hydroxyphenylethanol or its prodrug is 1~50mg in object preparation.
In accordance with the purpose of the invention, it is preferable that in unit medicament preparation the content of p-hydroxyphenylethanol or its prodrug be 5~ 40mg。
In accordance with the purpose of the invention, it is preferable that in unit medicament preparation the content of p-hydroxyphenylethanol or its prodrug be 5~ 20mg。
P-hydroxyphenylethanol of the invention or its prodrug can be used for preparing the drug for inhibiting bacterial community induction.The present invention P-hydroxyphenylethanol or its prodrug the bacterial community of chromabacterium biolaceum can be inhibited to incude but do not influence the normal life of chromabacterium biolaceum It is long.P-hydroxyphenylethanol of the invention or its prodrug can inhibit the bacterial community of Pseudomonas aeruginosa to incude but do not influence Pseudomonas aeruginosa Normal growth.
Detailed description of the invention
Fig. 1 is the active ingredients result of p-hydroxyphenylethanol in embodiment 1.
Fig. 2 be in embodiment 1 p-hydroxyphenylethanol to the thalli growth of chromabacterium biolaceum CV026 and violacein yield It influences.
Fig. 3 is p-hydroxyphenylethanol in embodiment 2 to Pseudomonas aeruginosa thallus, pyo, elastoser and albumen The influence of the yield of hydrolase.
Fig. 4 A is the influence that methanol forms the biofilm of Pseudomonas aeruginosa in embodiment 3.
Fig. 4 B is the influence that azithromycin forms the biofilm of Pseudomonas aeruginosa in embodiment 3.
Fig. 4 C is the influence that p-hydroxyphenylethanol forms the biofilm of Pseudomonas aeruginosa in embodiment 3.
Fig. 5 is the binding site of receptor protein 3QP1 and signaling molecule C6HSL in embodiment 4.
Fig. 6 is the binding site of receptor protein 3QP1 and p-hydroxyphenylethanol in embodiment 4.
Fig. 7 is the hydrophobic interaction of receptor protein 3QP1 and p-hydroxyphenylethanol in embodiment 4.
Specific embodiment
The present invention is further illustrated combined with specific embodiments below, but protection scope of the present invention is not limited to This.
The structure of p-hydroxyphenylethanol of the invention is as follows:
In the present invention, the molecular formula of the p-hydroxyphenylethanol is C8H10O2, molecular weight 138.P-hydroxyphenylethanol is Known compound can be used and is chemically synthesized, such as according to CN101225023, CN103232328A, CN103804147A Or method disclosed in CN104370706A etc. is prepared.P-hydroxyphenylethanol can also be obtained using the method for microbial fermentation It obtains, such as the method according to disclosed in CN109370967A or CN108753636A etc. is prepared.
In the present invention, the prodrug of p-hydroxyphenylethanol refer in vitro it is inactive or it is active it is smaller, in vivo through enzyme or non- The conversion of enzyme releases p-hydroxyphenylethanol and plays the compound of drug effect.
In the present invention, p-hydroxyphenylethanol or its prodrug have inhibition bacterial community induction effect, can be used for preparing tool There is the drug for inhibiting bacterial community induction effect.According to certain embodiments of the present invention, p-hydroxyphenylethanol of the invention or Its prodrug can inhibit the bacterial community of chromabacterium biolaceum to incude but not influence the normal growth of chromabacterium biolaceum.It is according to the present invention another Some embodiments, p-hydroxyphenylethanol of the invention or its prodrug can inhibit the bacterial community induction of Pseudomonas aeruginosa but not shadow Ring the normal growth of Pseudomonas aeruginosa.
In the present invention, the drug for inhibiting bacterial community induction can be using p-hydroxyphenylethanol and/or its prodrug as only One active constituent;Also may include other has the active constituent for inhibiting bacterial community induction effect, or does not have comprising itself Have and inhibits bacterial community induction effect but p-hydroxyphenylethanol and/or its prodrug can be assisted to play inhibition bacterial community induction The active constituent of effect.
In the present invention, the drug for inhibiting bacterial community induction can be bulk pharmaceutical chemicals, or pharmaceutical preparation.
In the present invention, the drug, which is formed, has the pharmaceutical preparation for inhibiting bacterial community induction effect.Unit medicament preparation In, the content of the p-hydroxyphenylethanol or its prodrug is 1~50mg, preferably 5~40mg, more preferably 5~20mg.Unit Pharmaceutical preparation refers to the preparation an of preparation and application unit, such as one tablet, one bag of granule, a capsule, a bottleneck Take liquid etc..The content of p-hydroxyphenylethanol or its prodrug, convenient for taking, is also convenient for sending out in above range in unit medicament preparation It waves and bacterial community is inhibited to incude effect.
In the present invention, the dosage form of the pharmaceutical preparation is unlimited, can for tablet, granule, capsule, pill, oral solution, Injection etc..The pharmaceutical preparation can also include pharmaceutically acceptable auxiliary material.The kind of the pharmaceutically acceptable auxiliary material Class is with no restrictions.Auxiliary material can be filler, corrigent, lubricant etc..Filler is also known as diluent, such as wheaten starch, wood Sweet potato starch, cornstarch, potato starch, dextrin, microcrystalline cellulose, lactose etc..The example of corrigent includes but is not limited to sweet tea Synanthrin glycosides, glycyrrhizin, mogroside, acesulfame potassium, Aspartame, Sucralose, isomaltoketose etc..Examples of lubricant includes But be not limited to magnesium stearate, talcum powder, superfine silica gel powder, magnesium laurylsulfate etc..
The LB culture medium that following embodiment uses is as follows:
Solid LB media: peptone 1%, yeast extract 0.5%, NaCl 1%, agar powder 2%, deionized water 100ml。
LB liquid medium: peptone 1%, yeast extract 0.5%, NaCl 1%, deionized water 100ml.
The active testing of 1 p-hydroxyphenylethanol of embodiment inhibition chromabacterium biolaceum quorum sensing
1. experimental principle
(1) bacterial community induction (QS) indicator bacteria chromabacterium biolaceum CV026 is signaling molecule C6HSL synthase gene cviI is lacked Mutant is lost, C6HSL signaling molecule is added in external source, its quorum sensing can be induced to generate violacein.If certain compound has There is quorum-quenching active, then the compound can be such that violacein yield reduces.
(2) synthesis of violacein is strictly to be regulated and controled by the bacterial community induction system of chromabacterium biolaceum, passes through analysis The thalli growth of chromabacterium biolaceum and the yield of violacein, it can be determined that whether some compound has bacterial community induction suppression System activity.
2. experimental method
2.1 chromabacterium biolaceum plate screening methods
Chromabacterium biolaceum CV026 is activated overnight.The 20mL solid LB media melted is cooled to 28 DEG C, 20 μ L cards are added The signaling molecule C of that mycin, 100 μ L6The chromabacterium biolaceum CV026 of HSL and 400 μ L activation, is poured on plate, to plate after mixing After solidification, 4 culture medium holes are made a call to punch, are separately added into 0.5mg/mL para hydroxybenzene in above-mentioned 3 culture medium holes Methanol and conduct is added in ethyl alcohol, 1mg/mL p-hydroxyphenylethanol and 1.5mg/mL p-hydroxyphenylethanol, remaining 1 culture medium hole Blank control group.After being incubated overnight at 28 DEG C, observe at above-mentioned 4 culture medium holes transparent haloing whether occur.
2.2 chromabacterium biolaceum shaking flask screening techniques
After chromabacterium biolaceum CV026 is activated overnight, it is inoculated into the LB liquid medium of the sterilizing of 20mL, chromabacterium biolaceum The inoculum concentration of CV026 is the 2vol% of LB liquid medium volume;The signaling molecule of 20 μ L kanamycins and 100 μ L is added C6P-hydroxyphenylethanol is added into shaking flask by HSL, formed various concentration gradient be 0.1mg/mL, 0.2mg/mL, 0.3mg/mL, The p-hydroxyphenylethanol solution of 0.4mg/mL and 0.5mg/mL, using methanol as blank control group.150rpm is cultivated at 28 DEG C 12h.Cultivate 12h after, take 1mL chromabacterium biolaceum bacterium solution in 1.5mL centrifuge tube, 12000rpm, 10min, chromabacterium biolaceum thallus and Violacein precipitates together, removes supernatant, and 1mL DMSO is added into centrifuge tube, re-dissolves chromabacterium biolaceum thallus and purple Bacillin, 12000rpm, 10min are centrifuged again, and violacein is dissolved in formation violacein liquid in supernatant DMSO, 1mL ddH is added in chromabacterium biolaceum bacterial sediment for chromabacterium biolaceum bacterial sediment, Aspirate supernatant2O weight is molten, obtains chromabacterium biolaceum Thallus liquid.The violacein liquid and chromabacterium biolaceum thallus liquid for taking 200 μ L respectively measure OD value with microplate reader in 96 microwell plates, The wavelength of violacein is 585nm, and the wavelength of chromabacterium biolaceum thallus is 600nm.
3. experimental result
3.1 chromabacterium biolaceum plate screenings
Experimental result is referring to Fig. 1.0.5mg/mL p-hydroxyphenylethanol, 1mg/mL p-hydroxyphenylethanol and 1.5mg/mL is added Occur the haloing of White-opalescent at the culture medium hole of p-hydroxyphenylethanol, and as the concentration of p-hydroxyphenylethanol is higher, Haloing is also bigger.The above results show that p-hydroxyphenylethanol is able to suppress violacein synthesis, and p-hydroxyphenylethanol is to purple The bacterial community induction system of bacillus has inhibitory activity.
3.2 chromabacterium biolaceum shaking flask is screened
Using the concentration of p-hydroxyphenylethanol as abscissa, using the absorbance at 600nm and 585nm as ordinate, analysis P-hydroxyphenylethanol is in 0.1~0.5mg/ml concentration range, the change of the yield of chromabacterium biolaceum thalli growth and violacein Change (referring to fig. 2).The above results show that p-hydroxyphenylethanol does not have an impact the growth of chromabacterium biolaceum, but with concentration Increase, violacein yield is gradually reduced and in concentration dependent, when p-hydroxyphenylethanol concentration is 0.5mg/mL, to purple The amount of suppression of color bacillin has reached 53.48%, illustrates that p-hydroxyphenylethanol has the bacterial community induction system of chromabacterium biolaceum There is good inhibitory activity.
The active testing of 2 p-hydroxyphenylethanol of embodiment inhibition Pseudomonas aeruginosa quorum sensing
1. experimental method
1.1 pyo yield
Pseudomonas aeruginosa P.aeruginosa PA01 is activated to logarithmic phase, and is diluted to OD600It is 0.05, then average mark For 7 groups (p-hydroxyphenylethanol groups of blank control group, positive controls and 5 various concentrations);Wherein, it is separately added into pair for 5 groups Hydroxylphenylethyl alcohol, forming various concentration gradient is 0.1mg/mL, 0.2mg/mL, 0.3mg/mL, 0.4mg/mL and 0.5mg/mL P-hydroxyphenylethanol solution;In addition, using methanol as blank control group, using the azithromycin of 0.2mg/mL as positive control Group;37 DEG C, shake culture 12h.It is centrifuged off Pseudomonas aeruginosa thallus, takes 5mL supernatant that 3mL chloroform is added, chloroform is mutually transferred to New eppendorf pipe, and the 0.2mol/L hydrochloric acid of 1mL is added, after mixing well extraction, upper strata aqueous phase is collected by centrifugation, with enzyme mark Instrument measures the OD value at wavelength 520nm.
1.2 elastin laminin production of enzyme
Pseudomonas aeruginosa P.aeruginosa PA01 is activated overnight.By the Pseudomonas aeruginosa P.aeruginosa after activation PA01 is inoculated into LB liquid medium, and the inoculum concentration of Pseudomonas aeruginosa P.aeruginosa PA01 is LB liquid medium volume 1vol%;Then 7 groups (p-hydroxyphenylethanol groups of blank control group, positive controls and 5 various concentrations) are equally divided into; Wherein, 5 groups of p-hydroxyphenylethanols for being separately added into 0.1mg/mL, 0.2mg/mL, 0.3mg/mL, 0.4mg/mL and 0.5mg/mL are molten Liquid;In addition, using methanol as blank control group, using the azithromycin of 0.2mg/mL as positive controls;In 37 DEG C, 150rmp Lower culture 12h.It takes bacterium solution to be centrifuged, 0.22 μm of nylon membrane of supernatant is filtered, take 100 μ L supernatants that 10mg elastin laminin-is added Congo red and 900 μ L Na2HPO4(pH 7.0), shake culture 2h at 37 DEG C after mixing.10000rpm is centrifuged 10min, takes Clear liquid measures absorbance at 495nm.
1.3 proteolysis production of enzyme
Pseudomonas aeruginosa P.aeruginosa PA01 is activated overnight.By the Pseudomonas aeruginosa P.aeruginosa after activation PA01 is inoculated into LB liquid medium, and the inoculum concentration of Pseudomonas aeruginosa P.aeruginosa PA01 is LB liquid medium volume 1vol%;Then 7 groups (p-hydroxyphenylethanol groups of blank control group, positive controls and 5 various concentrations) are equally divided into; Wherein, 5 groups of p-hydroxyphenylethanols for being separately added into 0.1mg/mL, 0.2mg/mL, 0.3mg/mL, 0.4mg/mL and 0.5mg/mL are molten Liquid;Other 2 groups, using methanol as blank control group, using the azithromycin of 0.2mg/mL as positive controls;37 DEG C, 12h is cultivated under 150rpm.It takes bacterium solution to be centrifuged, 0.22 μm of nylon membrane of supernatant is filtered, take 100 μ L supernatants that 400 μ L are added 50mmol/L K containing 0.8% azo-casein2HPO4(pH 7.0) solution, cultivates 3h at 30 DEG C after mixing.Then it is added The HCl solution of 1.5mol/L is placed in reacts 10min on ice, and after centrifugation, the NaOH solution of 0.5mol/L is added in supernatant;Again from After the heart, supernatant is taken to measure absorbance at 440nm.
2. experimental result
Experimental result is referring to Fig. 3.From the figure 3, it may be seen that 4- hydroxylphenylethyl alcohol does not inhibit thallus when concentration is lower than 0.5mg/mL Growth, and positive controls azithromycin (AZM) has apparent bacteriostasis.Compared with blank control group, with 4- hydroxy benzenes The concentration of ethyl alcohol increases, and the yield of pyo, elastoser and proteolytic enzyme gradually decreases.Although azithromycin It is particularly evident to the virulence factor inhibitory effect of Pseudomonas aeruginosa P.aeruginosa PA01, but it as antibiotic to bacterium Growth also has apparent inhibitory effect, when azithromycin concentration is only 0.2mg/mL in positive controls, to the inhibiting rate of thallus Up to 44.8%.It is above-mentioned the experiment results show that p-hydroxyphenylethanol is to the bacterial community of Pseudomonas aeruginosa P.aeruginosa PA01 Induction system has good inhibitory activity.
The analysis that 3 p-hydroxyphenylethanol of embodiment inhibits the biofilm of Pseudomonas aeruginosa to be formed
1. experimental principle
The intervention school-based of bacterium plays a significant role the formation of biofilm and stable structure, inhibits Pseudomonas aeruginosa The intervention school-based of P.aeruginosa PA01 can effectively reduce biofilm and be formed, and improve drug susceptibility.
2. experimental method
The SEM of 2.1 biofilms is imaged
Pseudomonas aeruginosa P.aeruginosa PA01 is activated overnight.By the Pseudomonas aeruginosa P.aeruginosa after activation PA01 is inoculated into LB liquid medium, and the inoculum concentration of Pseudomonas aeruginosa P.aeruginosa PA01 is LB liquid medium volume 1vol%;Then 3mL bacterium solution is added in six orifice plates, and is put into sterile slide, is next separately added into p-hydroxyphenylethanol (p-hydroxyphenylethanol group), 0.2mg/mL azithromycin (positive controls) and methanol (blank control group), 37 DEG C of stationary cultures After 48h, bacterium solution is siphoned away, and clean slide with sterile PBS, then fixed for 24 hours with 2.5% glutaraldehyde at room temperature, then used PBS is washed, and removes glutaraldehyde, then with ethanol dehydration 15 minutes of gradient concentration (50%, 70%, 80%, 90%), finally use 100% ethanol dehydration three times, each 10min.Metal spraying observation.
3. experimental result
Experimental result A~4C referring to fig. 4.Remain unchanged surface compact, cell of the biofilm of blank control group is completely in stub Shape is wrapped in film;The biofilm and cell of positive controls are destroyed by azithromycin, and graininess is presented;Para hydroxybenzene The biofilm of ethanol group is destroyed by p-hydroxyphenylethanol, but the cell of bacterium is not destroyed by p-hydroxyphenylethanol, this says Bright p-hydroxyphenylethanol can destroy biofilm, it is exposed outside make bacterium, but bacterium is complete, be normal corynebacterium, into And illustrate p-hydroxyphenylethanol to the cell of bacterium without destructiveness, that is to say, that p-hydroxyphenylethanol does not influence bacterium and normally gives birth to It is long, only inhibit bacterial community induction system.
The Molecular mechanism analysis on bio of bacterial community induction system is quenched in 4 p-hydroxyphenylethanol of embodiment
1. molecule simulation method
The molecule between p-hydroxyphenylethanol and receptor protein 3QP1 is carried out with molecular docking software Autodock first Then docking determines knot with the combination of molecular dynamics software gramacs simulation p-hydroxyphenylethanol and receptor protein 3QP1 again Coincidence point and key amino acid site.
2. sunykatuib analysis result
Sunykatuib analysis result is referring to Fig. 5~7.P-hydroxyphenylethanol and signaling molecule C6In HSL different active pockets, two The hydrogen bond and hydrophobic forces of person is entirely different, and p-hydroxyphenylethanol is with the receptor protein 3QP1 key amino acid for forming hydrogen bond GLU112, gLY138 and ARg163, hydrophobic forces Ser137, Met110, Arg159 and gly158.P-hydroxyphenylethanol with The binding site of receptor protein 3QP1 is in the bond area DNA, and the Binding change of the two activity conformation of receptor protein prevents The normal transcription of downstream gene, and then block the pathogenic behavior of quorum sensing regulation.This mechanism of action can be used for instructing new The research and development of type antibacterials, for treating infection caused by drug tolerant bacteria.
By above-mentioned experiment it is found that p-hydroxyphenylethanol has good inhibitory activity to bacterial community induction system, but not Influence bacterium normal growth.Above-mentioned experiment shows that p-hydroxyphenylethanol lives to bacterial community induction system with good inhibition Property, it can be used for preparing the drug for inhibiting bacterial community induction.
Present invention is not limited to the embodiments described above, without departing from the essence of the present invention, this field skill Any deformation, improvement, the replacement that art personnel are contemplated that each fall within the scope of the present invention.

Claims (10)

1. p-hydroxyphenylethanol or its prodrug are used to prepare the purposes for inhibiting the drug of bacterial community induction, the para hydroxybenzene second Alcohol has the structure as shown in formula (I):
2. purposes according to claim 1, which is characterized in that the drug forms the drug system for inhibiting bacterial community induction Agent;The pharmaceutical preparation includes the p-hydroxyphenylethanol or its prodrug, also includes pharmaceutically acceptable auxiliary material.
3. purposes according to claim 1, which is characterized in that the drug is made with the p-hydroxyphenylethanol or its prodrug For sole active agent.
4. purposes according to claim 1, which is characterized in that the drug forms the bacterial flora for inhibiting chromabacterium biolaceum The pharmaceutical preparation that body-sensing is answered.
5. purposes according to claim 4, which is characterized in that the drug forms the purple bar for inhibiting chromabacterium biolaceum The yield of rhzomorph but do not influence chromabacterium biolaceum normal growth pharmaceutical preparation.
6. purposes according to claim 1, which is characterized in that the drug forms the bacterial flora for inhibiting Pseudomonas aeruginosa The pharmaceutical preparation that body-sensing is answered.
7. purposes according to claim 6, which is characterized in that the drug forms the green pus bacterium for inhibiting Pseudomonas aeruginosa Element, elastoser and proteolytic enzyme yield but do not influence Pseudomonas aeruginosa normal growth pharmaceutical preparation.
8. described in any item purposes according to claim 1~7, which is characterized in that the drug, which is formed, inhibits bacterial flora body-sensing The pharmaceutical preparation answered;The content of p-hydroxyphenylethanol or its prodrug is 1~50mg in unit medicament preparation.
9. purposes according to claim 8, which is characterized in that p-hydroxyphenylethanol or its prodrug in unit medicament preparation Content is 5~40mg.
10. purposes according to claim 8, which is characterized in that p-hydroxyphenylethanol or its prodrug in unit medicament preparation Content be 5~20mg.
CN201910398611.9A 2019-05-14 2019-05-14 P-hydroxyphenylethanol is used to prepare the purposes for inhibiting the drug of bacterial community induction Pending CN110063948A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910398611.9A CN110063948A (en) 2019-05-14 2019-05-14 P-hydroxyphenylethanol is used to prepare the purposes for inhibiting the drug of bacterial community induction

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910398611.9A CN110063948A (en) 2019-05-14 2019-05-14 P-hydroxyphenylethanol is used to prepare the purposes for inhibiting the drug of bacterial community induction

Publications (1)

Publication Number Publication Date
CN110063948A true CN110063948A (en) 2019-07-30

Family

ID=67370730

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910398611.9A Pending CN110063948A (en) 2019-05-14 2019-05-14 P-hydroxyphenylethanol is used to prepare the purposes for inhibiting the drug of bacterial community induction

Country Status (1)

Country Link
CN (1) CN110063948A (en)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105663244A (en) * 2016-01-04 2016-06-15 中国石油大学(华东) Fig leaf extract with bacterium colony induction quenching activity, and use thereof
CN105899221A (en) * 2013-12-23 2016-08-24 医疗品牌研究有限公司 Dermatological composition based on algae and olive leaf extracts
CN107473980A (en) * 2017-08-28 2017-12-15 浙江工业大学 A kind of application of amides compound in bacterial community sensing activity inhibitor is prepared
CN107595822A (en) * 2017-08-24 2018-01-19 广东省微生物研究所(广东省微生物分析检测中心) Farnesol is preparing the application in suppressing the generation of pseudomonas aeruginosa pyo and biofilm formation medicine
CN107841523A (en) * 2017-10-19 2018-03-27 浙江大学 Triterpene substance method is extracted from Inonotus obliquus using the induction of quorum sensing molecule
CN107929742A (en) * 2017-12-18 2018-04-20 海南大学 The anti-infective pharmaceutical applications of hordenine or its joint antibiotic

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105899221A (en) * 2013-12-23 2016-08-24 医疗品牌研究有限公司 Dermatological composition based on algae and olive leaf extracts
CN105663244A (en) * 2016-01-04 2016-06-15 中国石油大学(华东) Fig leaf extract with bacterium colony induction quenching activity, and use thereof
CN107595822A (en) * 2017-08-24 2018-01-19 广东省微生物研究所(广东省微生物分析检测中心) Farnesol is preparing the application in suppressing the generation of pseudomonas aeruginosa pyo and biofilm formation medicine
CN107473980A (en) * 2017-08-28 2017-12-15 浙江工业大学 A kind of application of amides compound in bacterial community sensing activity inhibitor is prepared
CN107841523A (en) * 2017-10-19 2018-03-27 浙江大学 Triterpene substance method is extracted from Inonotus obliquus using the induction of quorum sensing molecule
CN107929742A (en) * 2017-12-18 2018-04-20 海南大学 The anti-infective pharmaceutical applications of hordenine or its joint antibiotic

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
AIPING CHANG等: "Tyrosol from marine Fungi, a novel Quorum sensing inhibitor against Chromobacterium violaceum and Pseudomonas aeruginosa", 《BIOORGANIC CHEMISTRY》 *
DIANA MARTÍNEZ-MATAMOROS等: "BÚSQUEDA DE BACTERIAS MARINAS COMO FUENTE DE INHIBIDORES DE QUORUM SENSING (IQS): PRIMER ESTUDIO QUIMICO DE Oceanobacillus profundus(RKHC-62B)", 《VITAE, REVISTA DE LA FACULTAD DE CIENCIAS FARMACÉUTICAS Y ALIMENTARIAS》 *
FASEELA HAMZA等: "Chapter 16 Marine Biodiversity As a Resource for Bioactive Molecules As Inhibitors of Microbial Quorum Sensing Phenotypes", 《BIOTECHNOLOGICAL APPLICATIONS OF QUORUM SENSING INHIBITORS》 *
JIN-WEI ZHOU等: "Hordenine: A Novel Quorum Sensing Inhibitor and Antibiofilm Agent against Pseudomonas aeruginosa", 《J. AGRIC. FOOD CHEM.》 *
SHAYMAA HASSAN ABDEL-RHMAN等: "Effect of Tyrosol and Farnesol on Virulence and Antibiotic Resistance of Clinical Isolates of Pseudomonas aeruginosa", 《BIOMED RESEARCH INTERNATIONAL》 *

Similar Documents

Publication Publication Date Title
Ezziyyani et al. Biological control of Phytophthora root rot of pepper using Trichoderma harzianum and Streptomyces rochei in combination
Vasavi et al. Anti-quorum sensing activity of flavonoid-rich fraction from Centella asiatica L. against Pseudomonas aeruginosa PAO1
Heo et al. Diphlorethohydroxycarmalol isolated from Ishige okamurae, a brown algae, a potent α-glucosidase and α-amylase inhibitor, alleviates postprandial hyperglycemia in diabetic mice
US7427408B2 (en) Quorum sensing and biofilm formation
CN109966321A (en) The composition being used for from particulate matter toxicity protection cell and tissue comprising lactobacillus casei bacterial strain
KR20120021349A (en) Functional food and pharmaceutical composition for treatment and prevention of diabetes using yerusalem artichoke fermented by lactic acid bacteria
Gupta et al. The implications of quorum sensing inhibition in bacterial antibiotic resistance-with a special focus on aquaculture
KR101466317B1 (en) A composition for inhibiting cancer metastasis comprising Hwangryunhaedoktang or its product fermented by lactic acid bacteria
Mihalik et al. Quorum sensing modulators of Pseudomonas aeruginosa characterized in Camellia sinensis
KR20170111763A (en) Pharmaceutical Composition for Preventing or Treating Enteric Diseases Caused by Clostridium difficile Comprising Lactobacillus acidophilus KCNU
WO2017124970A1 (en) Dicaffeoyl-spermidine derivative glycoside and use thereof
CN110063948A (en) P-hydroxyphenylethanol is used to prepare the purposes for inhibiting the drug of bacterial community induction
KR102517926B1 (en) Composition for preventing or treating gastric cancer comprising narcenicin A1 derivative
Huang et al. Cajaninstilbene acid analogues as novel quorum sensing and biofilm inhibitors of Pseudomonas aeruginosa
CN103002892B (en) Containing MA and derivant thereof the compositions with angiogenesis inhibitor effect as effective ingredient
KR101234582B1 (en) Composition for α-glucosidase inhibitory activity
JP4328058B2 (en) Composition for preventing diabetic complications
KR102143081B1 (en) Composition comprising carpomitra costata(stackhouse) batters extract for preventing or treating osteoarthritis
CN110151741A (en) The new opplication of protocatechualdehyde
JP5220862B2 (en) Novel compound signamycin, production method thereof, and use thereof
JP2008074734A (en) Ameliorating agent for insulin resistance
CN111840340A (en) Application of pomegranate bark tannin in preparation of medicine for inhibiting bacterial quorum sensing system
KR20120137127A (en) Composition comprising tea extract and lactic acid bacteria
TW200926986A (en) Quorum sensing inhibitor
KR101343367B1 (en) Compositions comprising lichen-forming fungi or scytalone for preventing and treating diabetes mellitus

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