CN108003099A - A kind of double benzyl tetrahydro isoquinoline class compounds and its preparation method and application - Google Patents
A kind of double benzyl tetrahydro isoquinoline class compounds and its preparation method and application Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/18—Aralkyl radicals
- C07D217/20—Aralkyl radicals with oxygen atoms directly attached to the aromatic ring of said aralkyl radical, e.g. papaverine
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Abstract
The present invention relates to field of medicaments, this application provides a kind of double benzyl tetrahydro isoquinoline class compounds and preparation method thereof, which has Formulas I or a Formula II general structure, in Formulas I and Formula II, R1、R2、R3、R4、R5、R6、R7And R8Independently selected from hydrogen or methyl.Double benzyl tetrahydro isoquinoline class compounds in the present invention can suppress the biomembrane of pseudomonas aeruginosa 9027, pseudomonas aeruginosa 27853 and tolerant Pseudomonas aeruginosa, show that double benzyl tetrahydro isoquinoline class compounds of the present invention can be by the intervention school-based that inhibits bacteria, so as to reach the growth that can not inhibited bacteria while bacterial virulence and pathogenicity is reduced, the effect of bacterial drug resistance is not likely to produce.Also, the present invention provides purposes of the double benzyl tetrahydro isoquinoline class compounds in quorum-quenching medicine is prepared.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a kind of double benzyl tetrahydro isoquinoline class compounds and its preparation side
Method and application.
Background technology
Lotus nut (Plumula nelumbinis), also known as the lotus heart of a lotus seed, the bitter heart of a lotus seed, lotus nut, see Tang end earliest《Feeding habits sheet
Grass》In, it is the drying plumule in the perennial water plant lotus mature seed of Nymphaeceae；Its main place of production be distributed in China Hunan,
Hubei, Fujian, Jiangsu, Zhejiang, Jiangxi etc. save.Lotus nut is cold in nature, bitter, the thoughts of returning home, kidney channel, has clearing away the heart fire and tranquillizing, restoring normal coordination between heart and kidney
And the effect of unsmoothing the sperm and stopping bleeding, for treating the diseases such as the invasion of pericardium by heat, coma and delirium, breakdown of the normal physiological coordination between the heart and the kidney, insomnia seminal emission and blood-head haematemesis, it is
One of common Chinese medicine with " clearing heat and detoxicating " effect.
The chemical composition of lotus nut includes：Double benzyl tetrahydro isoquinoline Alkaloids, monobenzyl tetrahydroisoquinolicompounds biology
Alkali, flavonoids, sterol and organic acid, volatile oil etc., double benzyl tetrahydro isoquinoline Alkaloids therein are lotus nut
Characteristic chemical constituent, and its content is higher.The document of system reviews lotus nut finds that modern pharmacology and clinical research also indicate that, lotus
The sub- heart is common to pseudomonas aeruginosa, bacillus salmonella, staphylococcus aureus, Escherichia coli, bacillus subtilis etc. thin
Bacterium is respectively provided with stronger inhibitory action.
Double benzyl tetrahydro isoquinoline class compounds be it is a kind of in plant kingdom's distribution limitation, structure type is various, physiological activity
Extensive native dimeric alkaloid；It is most in them to be present in more carpel monoids more original in plant kingdom, including lotus
The lotus nut alkaloid compound such as heart alkali, isoliensinine, neferine.Lotus nut alkaloid compound is proposed from Chinese medicine lotus nut
A kind of Bisbenzylisoquinolincompounds monoether of bonding alkaloid, can inhibit the common bacterias such as pseudomonas aeruginosa, and there is decompression, the anti-rhythm of the heart to lose
Often, adrenal gland α acceptors are blocked and suppress the effect such as calcium release.Research in recent years shows, this kind of compound is in antimalarial, anti-
Scorching, cardiovascular aspect has good physiological activity, is a kind of up-and-coming component.
The content of the invention
In view of this, the present invention provides a kind of double benzyl tetrahydro isoquinoline class compounds and its preparation method and application, this
Invent the double benzyl tetrahydro isoquinoline class compounds provided has good activity to suppressing pseudomonas aeruginosa.
The present invention provides a kind of double benzyl tetrahydro isoquinoline class compounds, has Formulas I or Formula II general structure：
In Formulas I and Formula II, R1、R2、R3、R4、R5、R6、R7And R8Independently selected from hydrogen (H) or methyl (CH3).The present invention carries
What is supplied is Bisbenzyltetrahydroisoquinoline class compound, belongs to lotus nut alkaloid compound.In some embodiments of the present invention
In, double benzyl tetrahydro isoquinoline class compounds are：Any one in formula 1, formula 2 and structural compounds shown in formula 3, this
It is noval chemical compound.
Compared with prior art, the present invention provides a kind of novel double benzyl tetrahydro isoquinoline class compounds of structure, tool
There are Formulas I or Formula II general structure.Experimental result shows that double benzyl tetrahydro isoquinoline class compounds in the present invention can suppress
The biomembrane of pseudomonas aeruginosa 9027, pseudomonas aeruginosa 27853 and tolerant Pseudomonas aeruginosa, it is shown that of the invention is double
Benzyl tetrahydro isoquinoline class compound can be by the intervention school-based inhibited bacteria, can be in reduction bacterial poison so as to reach
The growth not inhibited bacteria while power and pathogenicity, is not likely to produce the effect of bacterial drug resistance.Also, newization in the present invention
Compound biomembrane inhibitory action, phase in both pseudomonas aeruginosas of ATCC 27853 (μ g/mL) and persister (μ g/mL)
Than showing preferable activity in the existing compound such as liensinine, neferine.
The present invention provides double benzyl tetrahydro isoquinoline class compounds described above and is preparing quorum-quenching medicine
Purposes in thing.In particular it relates to prepare the quorum sensing for suppressing pseudomonas aeruginosa or tolerant Pseudomonas aeruginosa
Application in medicine.
In the present invention, double benzyl tetrahydro isoquinoline class compounds can by suppress pseudomonas aeruginosa and/or
Tolerant Pseudomonas aeruginosa biomembrane, plays the effect of resisting pseudomonas aeruginosa and/or tolerant Pseudomonas aeruginosa.Specifically,
Double benzyl tetrahydro isoquinoline class compounds in the embodiment of the present invention can suppress pseudomonas aeruginosa 9027, P. aeruginosa
Bacterium 27853 and the biomembrane of tolerant Pseudomonas aeruginosa, the intervention school-based inhibited bacteria.The double benzyl tetrahydros of system reviews are different
The pertinent literature of quinolines and lotus nut, not yet finds that it inhibits bacteria the document report of intervention school-based.
Described bacterial community sensing (Quorumsensing, the QS) system, becomes study new antimicrobial agent in recent years
The important target of medicine.QS is in bacterial cell or a kind of mode of intercellular signal transmission, by monitoring some signaling molecules
(also known as autoinducer) such as concentration of homoserine lactone (acyl-homoserine lactone, AHL), to control simultaneously
Coordinate whole bacterial community behavior, surrounding environment is stimulated jointly and is made a response, greatly enhances the existence of whole bacterial community
Ability.
The pseudomonas aeruginosa (P.aeruginosa), has the very strong energy that biomembrane is formed in tissue surface
Power, and its QS system research obtain it is also the most thorough.Therefore, the embodiment of the present invention selects pseudomonas aeruginosa to be studied for this project
Pattern bacterium.Pseudomonas aeruginosa is a kind of important conditioned pathogen, usually causes respiratory tract infection, pneumonia, the urinary tract sense
The inside-hospital infections such as dye, it is considered to be the third-largest pathogenic bacteria that patient infects during hospital, seriously endanger the mankind's
Health and life.The high inherent resistance to the action of a drug of pseudomonas aeruginosa is inseparable with its intervention school-based, which controls
Include the expression of nearly all virulence factor such as biomembrane, exotoxin, elastoser, hemolysin, pyo.These cause a disease
The factor determines pathogenecity of the pseudomonas aeruginosa to host.Wherein, biomembrane formation and diffusion be to cause
One important mechanisms of P.aeruginosa multidrug resistants.Portion authority's investigation of National Institutes of Health (NIH) issue
Report points out, human microbial is infected with being mediated by bacterial biofilm (Biofilm, BF) more than 80%.BF conducts
A kind of bacterial community behavior, it breaks up closely related with development and bacterial community sensing.Bacterial community induction system is completely thin
Bacterium, which can form development and differentiation, can normally, typically resist the biomembrane of fungicide, and bacterial community induction system is incomplete
Bacterium cannot then form typical biomembrane, the resistance of antibiotic is remarkably decreased, and is easily rinsed and right
Fungicide is sensitive.Therefore, by being quenched the QS systems of the formation of control bacterial biof iotalm and pathogen virulence factor expression, because not straight
Connect and inhibit bacteria growth, selection pressure will not be produced to bacterium, acquisition will be got a good chance of and act on novel targets, bacterium will not be made
The group for producing drug resistance feels inhibitor (QS inhibitors, QSI).
According to use above, an embodiment of the present invention provides a kind of quorum sensing to suppress medicine, the bacterial flora body-sensing
Should suppress medicine includes：Previously described double benzyl tetrahydro isoquinoline class compounds and pharmaceutically acceptable auxiliary material.
At present, with the extensive use of antibiotic, the drug resistance intensity of microorganism is higher and higher, Antibiotic Resistance is more and more wider, resistance to
The speed rising proportional to antibiotic sterilization capability that pharmacological property is formed.Drug resistance once produces, it will keeps.Antibiotic
It is continuing with, can is only that high antibody-resistant bacterium continues to provide selection pressure, promote its duplication, group structure and enjoy drug resistant gene jointly,
The quickening of multiple antibiotic resistant strain is caused to be formed.Therefore, antibiotic resistance has become the serious public health problem in the whole world.
China causes 80,000,000,000 yuan of medical expenses to increase because of abuse of antibiotics every year, while causes 80,000 patients bad anti-because of its
Should death.No matter because illness weight, operation size, all using antibiotic, and tend to high-titer antibiotic and often
A large amount of blindness long-time drug combinations, it is indivedual even to use more than 4 kinds of antibiotic in a short time and cause new antibody-resistant bacterium
Continuously emerge.Some experts even predict that China may take the lead in entering " rear antibiotic epoch ", that is, return to before antibiotic is found when
Generation.
China possesses extremely abundant Chinese medicine and natural pharmaceutical resources, and nearly ten thousand kinds of medicinal plant, provides for new drug discovery
Abundant material base and source.Moreover, carrying out antibacterial, anti-inflammatory with Chinese patent drug substitute antibiotics, there is adverse reaction and secondary work
With it is relatively small, do not produce the advantages that drug resistance.On the other hand, world medical circle does not have real meaning in the time 40 years existing
On new antibiotic be born.Therefore, many researchers focus on crude drug " antibiotic " in spite of oneself
On.Being found from traditional Chinese medicine resource equally has the alternative product of antibiotic of antibacterial anti-inflammatory curative effect, can solve to resist well
Raw this world-famous puzzle of element drug resistance.
Thus, it is a kind of drug-resistance bacteria medicine of non-antibiotic class that quorum sensing provided by the invention, which suppresses medicine, and is had
Help avoid antibiotics resistance problem.Double benzyl tetrahydro isoquinoline class compounds particularly therein, it is false for drug resistance verdigris
The biomembrane of monad is respectively provided with more suitable than positive drug furan ketone compound or more preferable inhibition, indicates of the invention double
Benzyl tetrahydro isoquinoline class compound is respectively provided with good inhibition for green pseudomonad and the green pseudomonad of drug resistance.
In some embodiments of the invention, according to mass percent, the quorum sensing, which suppresses medicine, may include 10%
~90% double benzyl tetrahydro isoquinoline class compounds and 10%~90% pharmaceutically acceptable auxiliary material.In the reality of the present invention
Apply in example, after previously described double benzyl tetrahydro isoquinoline class compounds are added pharmaceutically acceptable auxiliary material, prepare patent medicine
Acceptable preparation on.In a specific embodiment of the present invention, the quorum-quenching medicine is oral drugs, i.e.,
Its formulation is oral formulations.It is further preferred that the oral formulations are capsule, tablet or granule etc..
Capsule is that medicine is filled in hollow hard capsules or is sealed in elastomeric flexible capsule and manufactured solid
Preparation；Tablet is the Formulation suppressed after medicine is uniformly mixed with auxiliary material；Granule is by medicine and suitable auxiliary material
Coordinate and manufactured granular formulations, generally can be divided into soluble granule, suspension granule and effervescency granule.This hair
Bright supplementary product kind and preparation in each preparation etc. is not particularly limited；It is common to have diluent, absorbent, adhesive, wetting
Agent, disintegrant, lubricant, capsule material.Wherein, diluent such as sucrose, dextrin, lactose, mannitol, sorbierite, starch, crystallite
Cellulose etc.；Common absorbent is inorganic salts, such as aluminium hydroxide, magnesia.Adhesive such as sodium carboxymethylcellulose；Profit
Humectant such as water, alcohol, starch slurry etc..The crosslinking polyvinylpyrrolidone of disintegrant, dried starch etc.；Lubricant such as magnesium stearate, cunning
Mountain flour, polyethylene glycol etc..
The embodiment of the present invention additionally provides a kind of preparation method of double benzyl tetrahydro isoquinoline class compounds, including following step
Suddenly：
(1) lotus nut is subjected to refluxing extraction with solvent, then concentrates gained extracting solution, obtain concentrate；
(2) gained concentrate is adjusted into pH value to 2~5, filtering, obtains filtrate；
(3) gained filtrate is adjusted into pH value to 8~10, filtering, obtains total alkaloid medicinal extract；
(4) the total alkaloid medicinal extract is separated with chromatography, obtains double benzyls with Formulas I or Formula II general structure
Base tetrahydroisoquinolicompounds compounds：
In Formulas I and Formula II 2, R1、R2、R3、R4、R5、R6、R7And R8Independently selected from hydrogen or methyl.
The embodiment of the present invention mainly uses Acidic distillation, through chromatographic separation and purification method, to Plumula nelumbinis Alkaloid into
Row chemical composition separates, and obtains noval chemical compound.Double benzyl tetrahydro isoquinoline class compounds that the present invention obtains are false to suppressing verdigris
Monad etc. has good activity, beneficial to application.
The embodiment of the present invention can carry out refluxing extraction using lotus nut medicinal material as raw material with the solvent of 8~15 times of medicinal material weight,
Obtain extracting solution.In the present invention, the solvent may be selected from one kind or several in methanol, ethanol, acetone, ethyl acetate and water
Kind, it is preferably ethanol.The embodiment of the present invention can be multiple by refluxing extraction after lotus nut ethanol soaked overnight, merges extracting solution.
Wherein, the Extracting temperature of the refluxing extraction is preferably 10~150 DEG C, more preferably 60~140 DEG C；It is 3~5 times extractable, often
Secondary extraction time for 0.5 it is small when~80 it is small when, be preferably 1 it is small when~60 it is small when, more preferably 2 it is small when~30 it is small when.The present invention
The extracting solution of merging is carried out Conventional concentration by embodiment, obtains concentrate.
Obtained concentrate acid reagent is adjusted pH value to 2~5 by the embodiment of the present invention, preferable ph 3；Described
Acid reagent is usually the hydrochloric acid or sulfuric acid solution of 0.5%-5% mass concentrations.Then, gauze mistake of the embodiment of the present invention
Filter, obtains black paste precipitation (non-alkaloids material) and filtrate two parts.Then, the embodiment of the present invention uses gained filtrate
Alkaline reagent adjusts the pH value of solution to 8~10, preferable ph 9；The alkaline reagent can be ammonium hydroxide, milk of lime or
Sodium hydroxide.The embodiment of the present invention filters again, obtains total alkaloid medicinal extract.
After obtaining total alkaloid medicinal extract, the embodiment of the present invention carries out the total alkaloid medicinal extract using chromatography separation essence
System, obtains having Formulas I or double benzyl tetrahydro isoquinoline class compounds of Formula II general structure.Wherein, the chromatography can be
Normal phase chromatography, reverse-phase chromatography or exclusion chromatography, specifically include repeatedly silica gel column chromatography, open ODS column chromatographys,
The isolation and purification methods such as Sephadex LH-20 column chromatographys, preparative high performance liquid chromatography.In some embodiments of the invention,
Obtained double benzyl tetrahydro isoquinoline class compounds have 3 structure of formula 1, formula 2 or formula.
The preparation method of double benzyl tetrahydro isoquinoline class compounds described in the embodiment of the present invention, different from methyl lotus nut
The extracting method of the existing compound such as alkali；The method of the present invention is simple and easy to do, suitable for industrial application.
Embodiment
The technical solution in the embodiment of the present invention is clearly and completely described below, it is clear that described embodiment
Only part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, the common skill in this area
Art personnel all other embodiments obtained without making creative work, belong to the model that the present invention protects
Enclose.
For a further understanding of the application, the double benzyl tetrahydro isoquinoline classes provided with reference to embodiment the application
Compound and its preparation method and application is specifically described.
The extraction separation of 1 pair of benzyl tetrahydro isoquinoline class compound of embodiment and Structural Identification
(1) lotus nut 10.5kg is taken, after the ethanol soaked overnight with 12 times of 80% (v/v) of amount, refluxing extraction 3 times, extraction
Temperature is 130 DEG C, each 2h, merges extracting solution, is further concentrated to no alcohol taste；
(2) 1%HCl of concentrate in (1) is adjusted into pH to 3, then filtered through gauze obtains filtrate；
(3) filtrate in (2) is adjusted to the pH to 9 of solution with ammonium hydroxide, stands overnight, total alkaloid medicinal extract is obtained by filtration
(PNA)200g；
(4) successively using silica gel column chromatography (elution system repeatedly：The methylene chloride-methanol of 10%-100%), open ODS
Column chromatography (methanol-water of 30%-80%) and preparative high performance liquid chromatography (add 0.05% 3 second in 60% methanol-water
Amine), chemical composition separation is carried out to gained Plumula nelumbinis Alkaloid in (3), compound 1-3 (comp.1-3) is obtained.
The structure of compound 1-3 using technical appraisement such as NMR spectrums, is 3 new double benzyl tetrahydro isoquinolines
Class, their nuclear magnetic resonance13C-NMR、1H-NMR (400MHz, CDCl3) data are shown in Table 1.As known from Table 1, the knot of compound 1-3
Structure is successively as shown in formula 1, formula 2, formula 3.
1 embodiment of table, 1 gained compound 31-3's1H-NMR、13C-NMR data
A Nuclear Magnetic Resonance for Brooker company Bruker-400 (1H-NMR is 400MHz,13C-NMR is 100MHz)
B is unimodal to be represented with " (s) ", and bimodal to be represented with " (d) ", double doublet is represented with " (dd) ", multiplet " (m) " table
Show, the signal to overlap is represented with " (o) ", and c coupling constants (J values) are represented with Hz..
Note：13C-NMR：Carbon-13 nmr spectra；1H-NMR：Nuclear magnetic resonance spectroscopy；CDCl3：Chloroform.
The biomembrane Inhibition test of 2 pairs of benzyl tetrahydro isoquinoline class compounds of embodiment
Test compound：Using the bromo- 5- of furan ketone compound (Z) -4- (bromine methylene) -2 (5H)-furanones to be positive right
According to DMSO (dimethyl sulfoxide (DMSO)) for negative control, by double benzyl tetrahydro isoquinolines of positive drug and the compound 1-3 of the present invention
Quinoline class compound is configured to 32,64,128 μ g/mL respectively.
Experimental method：The compound to be tested that 100 μ L are prepared is separately added into orifice plate, is inoculated with 100 μ L bacterium solutions；Set
Blank control group (200 μ L of LB culture mediums) and negative control group (LB culture mediums and each 100 μ L of bacterium solution).It is Celsius that each group is placed in 37
Hatch in degree incubator；After 20h, hole endosexine bacterium solution is drawn, distillation water washing three times, washes away planktonic bacteria.Dry or baking oven
After drying, the crystal violet that 220 μ L concentration are 1% is added, room temperature places 30min, then distilled water carefully washing 3 times；Add 230
μ L95% ethanol dissolves biomembrane-crystal violet compound, and orifice plate absorbance, parallel determination are measured at microplate reader 630nm wavelength
Three times.Measurement result is shown in Table 2：
Suppression of 2 embodiment of table, the 1 pair of benzyl tetrahydro isoquinoline class compound for three kinds of aeruginosa biofilms is made
With
As seen from Table 2, the inhibition assay result of three kinds of aeruginosa biofilms is shown, double benzyls four of the invention
Hydrogen isoquinoline class compound is respectively provided with inhibition for the biomembrane of three kinds of pseudomonas aeruginosas, it is shown that double benzyls of the invention
Base tetrahydroisoquinolicompounds compounds can be by the intervention school-based inhibited bacteria, can be in reduction bacterial virulence so as to reach
And the growth not inhibited bacteria while pathogenicity, it is not likely to produce the effect of bacterial drug resistance.Particularly compound 1-3, for
The biomembrane of tolerant Pseudomonas aeruginosa is respectively provided with than positive drug furan ketone compound quite even preferably inhibition, table
Understand that the double benzyl tetrahydro isoquinoline class compounds of the present invention are respectively provided with well for green pseudomonad and the green pseudomonad of drug resistance
Inhibition.
Also, the noval chemical compound in the present invention is in ATCC 27853 (μ g/mL) and both verdigris of persister (μ g/mL)
Biomembrane inhibitory action in pseudomonad, preferable activity is shown compared to the existing compound such as liensinine, neferine.
3 resisting pseudomonas aeruginosa granule of embodiment
Formula composition：
1 10mg of compound in embodiment 1；
Lactose 15mg；
10% starch slurry 3mg.
The preparation process of resisting pseudomonas aeruginosa granule is：
(1) compound of formula I first with lactose mixing 10-15 minutes；
(2) 10% starch slurry softwood is added in (1), crosses 14 mesh sieves, it is dry after granulation；
(3) drying after 12 mesh sieves, whole grain by particle obtained by (2), up to the resisting pseudomonas aeruginosa particle of the present invention
Agent.
4 resisting pseudomonas aeruginosa capsule of embodiment
Formula composition：
The preparation process of resisting pseudomonas aeruginosa capsule is：
(1) compound of formula I first with lactose mixing 10-15 minutes；
(2) mixed 10-15 minutes after microcrystalline cellulose is added in (1)；
(3) mixed 3-5 minutes after talcum powder is added in (2)；
(4) mixture obtained by (3) is loaded into gelatine capsule shell, up to resisting pseudomonas aeruginosa capsule of the present invention.
5 overriding resistance pseudomonas aeruginosa tablet of embodiment
Formula composition：
The preparation process of overriding resistance pseudomonas aeruginosa tablet is：
(1) Formula II compound first with lactose mixing 10-15 minutes；
(2) 10% starch slurry softwood is added in (1), crosses 14 mesh sieves, it is dry after granulation, cross 12 mesh sieve whole grains；
(3) and then in (2) crospovidone and magnesium stearate are added, is mixed 3-5 minutes；
(4) by the tabletting after mixing of (3) resulting material, up to overriding resistance pseudomonas aeruginosa tablet of the present invention.
The biomembrane Inhibition test of 6 three kinds of compound formulations of embodiment
1 granule of compound of the preparation of Example 3,2 Capsule content of compound of the preparation of embodiment 4, embodiment 5
Obtained 3 tablet of compound, tests its inhibitory activity to biomembrane, specific testing procedure is the same as embodiment 2, test result respectively
It is shown in Table 3.
According to test result, it is a kind of antimicrobial agent medicine of non-antibiotic class that quorum sensing provided by the invention, which suppresses medicine,
Thing, and help avoid antibiotics resistance problem.Double benzyl tetrahydro isoquinoline class compounds particularly therein, it is for drug resistance
The biomembrane of pseudomonas aeruginosa is respectively provided with more suitable than positive drug furan ketone compound or more preferable inhibition, indicates this
The double benzyl tetrahydro isoquinoline class compounds of invention are respectively provided with for green pseudomonad and the green pseudomonad of drug resistance suppresses effect well
Fruit.
Suppression of the 3 pairs of benzyl tetrahydro isoquinoline class compound medicine preparations of table for three kinds of aeruginosa biofilms
Effect
The above is only the preferred embodiment of the present invention, it is noted that the professional technique for making the art
Personnel, without departing from the technical principles of the invention, are that by a variety of modifications to these embodiments, and these
Modification also should be regarded as the scope that the present invention should protect.
Claims (10)
1. a kind of double benzyl tetrahydro isoquinoline class compounds, have Formulas I or Formula II general structure：
In Formulas I and Formula II 2, R1、R2、R3、R4、R5、R6、R7And R8Independently selected from hydrogen or methyl.
2. double benzyl tetrahydro isoquinoline class compounds according to claim 1, it is characterised in that there is formula 1, formula 2 or formula 3
Structure：
3. double 3 benzyl tetrahydro isoquinoline class compounds as claimed in claim 1 or 2 are preparing quorum-quenching medicine
In purposes.
4. purposes according to claim 3, it is characterised in that the bacterial community is sensed as pseudomonas aeruginosa or drug resistance
The quorum sensing of pseudomonas aeruginosa.
5. the purposes according to claim 3 or 4, it is characterised in that the quorum-quenching medicine includes described
Double benzyl tetrahydro isoquinoline class compounds and pharmaceutically acceptable auxiliary material.
6. purposes according to claim 5, it is characterised in that the formulation of the quorum-quenching medicine is oral
Preparation.
7. purposes according to claim 6, it is characterised in that the oral formulations are capsule, tablet or granule.
8. a kind of preparation method of double benzyl tetrahydro isoquinoline class compounds, comprises the following steps：
(1) lotus nut is subjected to refluxing extraction with solvent, then concentrates gained extracting solution, obtain concentrate；
(2) gained concentrate is adjusted into pH value to 2~5, filtering, obtains filtrate；
(3) gained filtrate is adjusted into pH value to 8~10, filtering, obtains total alkaloid medicinal extract；
(4) the total alkaloid medicinal extract is separated with chromatography, obtains double benzyls four with Formulas I or Formula II general structure
Hydrogen isoquinoline class compound：
In Formulas I and Formula II 2, R1、R2、R3、R4、R5、R6、R7And R8Independently selected from hydrogen or methyl.
9. preparation method according to claim 8, it is characterised in that the solvent is selected from methanol, ethanol, acetone, acetic acid
One or more in ethyl ester and water.
10. preparation method according to claim 9, it is characterised in that the Extracting temperature of the refluxing extraction is 10~150
DEG C, when extraction time is 0.5~80 small.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11345941B2 (en) | 2019-09-20 | 2022-05-31 | Fudan University | Method for preparing (S)-1-benzyl-1,2,3,4,5,6,7,8-octahydroisoquinoline compound |
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| CN101862374A (en) * | 2010-06-12 | 2010-10-20 | 李宏 | Lotus plumule and new application of extractive thereof |
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| T.P.TIM CUSHNIE等: "Alkaloids: An overview of their antibacterial, antibiotic-enhancing and antivirulence activities", 《INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS》 * |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US11345941B2 (en) | 2019-09-20 | 2022-05-31 | Fudan University | Method for preparing (S)-1-benzyl-1,2,3,4,5,6,7,8-octahydroisoquinoline compound |
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