CN110141576A - A kind of compound is used to prepare the application in treatment oxidative damage related disease drug - Google Patents
A kind of compound is used to prepare the application in treatment oxidative damage related disease drug Download PDFInfo
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- 239000003814 drug Substances 0.000 title claims abstract description 18
- 229940079593 drug Drugs 0.000 title claims abstract description 16
- 230000004792 oxidative damage Effects 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 claims abstract description 3
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- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 claims description 12
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The object of the present invention is to provide a kind of application of compound in the drug of preparation treatment oxidative damage related disease, the cellular damage of hydrogen peroxide-induced can be effectively suppressed in compound of the present invention, improve cell growth rate, with significant anti-oxidative damage activity, it can be used as the potential treatment drug of oxidative damage related disease, provide new selection for new drug development and clinical treatment.
Description
Technical field
The invention belongs to field of medicine and chemical technology, and in particular to a kind of compound is used to prepare treatment oxidative damage related disease
Application in drug.
Background technique
Have the source various active oxygens (ROS) in viable organism, ROS can make various large biological molecules such as nucleic acid in body,
Oxidative damage occurs for lipid, protein, sugar etc., so as to cause a series of diseases.Under normal circumstances, DNA oxidative damage is high
Frequency, and due to the repair system of body and not perfect, it the DNA of oxidative damage and accumulates gradually by mutagenesis position, thus
Lead to the aging of certain cancers and body.Meanwhile studies have shown that endothelial dysfunction and oxidative stress in atherosclerosis shape
At leading role is played in the process, main inducing of the reactive oxygen species as oxidative stress promotes endothelial cell damage and function
The generation of energy obstacle, accelerates the generation and development of atherosclerosis.Due to not having also in the atherosclerosis subclinical stage
There is the therapy approach of direct antiatherosclerosis, so, the activity of inhibitory activity oxygen cluster is considered as improvement and prevention of arterial
Reasonable thinking [Orekhov AN, Sobenin IA, the Revin VV, Bobryshev of atherosclerotic disease
YV.Development of Antiatherosclerotic Drugs on the basis ofNatural Products
Using Cell Model Approach.Oxid Med Cell Longev.2015；2015:463797.].In addition, grinding in recent years
Studying carefully also found, the generation of the diseases such as cataract, age-related macular degeneration is also related with ROS, and [age-related macular compiles and edit blood plasma lipid peroxidation
The clinical meaning of matter and erythrocyte superoxide dismutase measurement, ophthalmology research, Chen Song etc., the 13rd phase of volume 1995,2].
In view of viable organism all the time all by endogenous or exogeneous reactivity oxygen class invasion, to induce a series of
Disease, such as atherosclerosis, cancer, cataract, age-related macular degeneration etc..Want fundamentally to prevent and treat these diseases,
Anti-oxidative damage be it is crucial [research of oxidative damage disease and Anti-oxidation teaditional Chinese medicine, Anhui Chinese Medicine College journal, Zhang Qiuju,
The 2nd phase of volume 1997,16].The chemicals that ROS damages body large biological molecule can be mitigated and eliminate by containing in certain Chinese herbal medicines
Matter, therefore they are to the therapeutic effect that a variety of diseases can obtain caused by oxidative damage.Such as: resveratrol is that one kind is deposited extensively
The natural being in the plants such as grape, peanut, polygonum cuspidate, Cassia, black false hellebore, modern research shows that it has extensive life
Object activity, treat inflammation, allergy, tumour, in terms of all applied, and the generation of these diseases with
DNA damage and lipid peroxidation closely related [resveratrol antioxidation and its control efficiency in related disease, Zhang Xiao
Spring etc., food and nutrition science, 2017,6 (2): 59-64].In order to provide more choosings to new drug development and clinical treatment
It selects, the substance for developing more anti-oxidative damages has positive effect.
Summary of the invention
The object of the present invention is to provide a kind of compounds to prepare the application in the drug for treating oxidative damage related disease,
Compound of the present invention has the structure as shown in following formula I:
Oxidative damage related disease of the present invention is selected from: atherosclerosis, cancer, cataract, age-related macular degeneration,
Inflammation.
Type I compound chemical name of the present invention be 3,4- Dimethoxyphenyl -1-O- β-D-arabinose-(1 →
6)-β-D- glucopyranoside (3,4-dimethoxyphenyl-1-O- β-D-apiofuranosyl- (1 → 6)-β-D-
Glucopyranoside), it can be extracted from natural plants and obtain or obtained by chemical synthesis.It can refer to public in the prior art
The specific method opened obtains, such as reported can be from the bark (Phenolic of Magnoliacea plant Cortex Magnoliae Officinalis for the prior art
Glycosides and other constituents from the bark of Magnolia officinalis,
Journal of Asian Natural Products Research, 2014, Vol.16, No.4,400-405), Lauraceae cortex cinnamomi
Bark (Identification ofCompounds from the Water Soluble Extract of
Cinnamomum cassia Barks and Their Inhibitory Effects against High-Glucose-
Induced Mesangial Cells, Molecules 2013,18,10930-10943) etc. the isolated type I compound.
Type I compound of the present invention comes from needles of pinus massoniana extract, to separate after the fresh pine needle water refluxing extraction of masson pine, being pure
Change obtains；Wherein purification procedures are, using conventional method by extract medicinal extract pass sequentially through macroreticular resin D101 column chromatography,
MCI column chromatography, ODS column chromatography, sephadex LH-20 column chromatography, YMC column chromatography, sephadex LH-20 column chromatography, silica gel
Column chromatography is isolated and purified；It specifically includes the following steps:
(1) it takes the fresh pine needle of masson pine appropriate, adds in 4 times of amount boiling water, refluxing extraction 1h, filter, 3 times of amounts are added again
Water, refluxing extraction 1 hour, filtering, medicinal extract was concentrated under reduced pressure to obtain in merging filtrate, spare；
(2) take medicinal extract obtained in step (1), it is water-dispersible after in batches loading to macroreticular resin D101, then successively with water,
20% 3 times of ethanol elution column volume collects 20% ethanol elution part, is concentrated and dried to obtain eluate a, spare；
(3) loading MCI column chromatographs after dissolving the eluate a of step (2) with water, successively passes through water, 10% ethanol elution.
10% ethanol eluate is collected, eluate b is concentrated and dried to obtain, it is spare；
(4) after the eluate b of step (3) being dissolved with water loading ODS column chromatograph, successively pass through water, 10% ethanol elution,
10% ethanol eluate is collected, eluate c is concentrated and dried to obtain, it is spare；
(5) after dissolving the eluate c of step (4) with 20% ethyl alcohol, sephadex LH-20 column chromatography for separation is carried out,
20% elution, collects the 3rd~4 times of column volume eluent, is concentrated and dried to obtain eluate d, spare；
(6) loading YMC column chromatographs after dissolving the eluate d of step (5) with water, is successively washed respectively with 2%, 5% ethyl alcohol
3 times of column volumes are taken off, 5% ethanol elution part is collected, are concentrated and dried to obtain eluate e, it is spare.
(7) loading sephadex LH-20 column chromatography for separation after dissolving eluate e in step (6) with 30% ethyl alcohol,
30% ethanol elution collects the 3rd times of column volume, is concentrated and dried to obtain eluate f, spare.
(8) by eluate f CH in step (7)2Cl2: loading silica gel column chromatography point after 95% ethyl alcohol (4:1, v/v) dissolution
From EtOAc:95% ethyl alcohol (6:1, v/v) elution by eluent point lamellae, makees exhibition with EtOAc:95% ethyl alcohol (4:1, v/v)
It opens agent to be analyzed, collects the eluent for showing principal spot on lamellae, be concentrated and dried to obtain eluate g.
(9) by eluate g CH in step (8)2Cl2: loading silica gel column chromatography point after 95% ethyl alcohol (4:1, v/v) dissolution
From through CH2Cl2: 95% ethyl alcohol (4:1, v/v) elution by eluent point lamellae, uses CH2Cl2: 95% ethyl alcohol (4:1, v/v)
It is analyzed as solvent, collects the eluent for showing single spot on lamellae, concentrate drying obtains type I compound.
The cellular damage of hydrogen peroxide-induced can be effectively suppressed in type I compound of the present invention, improves cell growth rate, tool
There is significant anti-oxidative damage activity, can be used as the potential treatment drug of oxidative damage related disease, is new drug development and clinic
Treatment provides new selection.
Specific embodiment
Experimental material used is as follows in the present invention:
Middle pressure chromatographic isolation gel (Middle Chromatogram Isolated Gel, MCI): producer:
Mitsubishi Chemical Corporation, model: CHP20/P50；
YMC is prepared filler (YMC): producer: YMC Co., Ltd. model: ODS-A-HG, S-50 μm；
Sephadex lh-20 (Sephadex LH-20): producer: GE Healthcare, Bio-SciencesAB, 18-
111μm；
C18 reversed-phase bonded silica (ODS): producer: Sepax Technologies, Inc, model: GP-C18,50 μm；
The fresh pine needle of masson pine: in January, 2015 is collected in Sichuan Province's Zigong City, reflects through Chengdu University of Traditional Chinese Medicine professor Yan Zhuyun
It is set to pinaceae plant Pineneedles of Pinus Massoniana Lamb (Pinus massoniana Lamb.)；
Macroreticular resin: Chengdu Ke Long chemical reagent factory, model: D101；
Endothelial cell culture base (Sciencell Research Laboratories, USA, Lot.No.22099)；
Fetal calf serum (Fetal bovine serum, FBS；Sciencell Research Laboratories, USA,
Lot.No.20540)；
Endothelial cell growth supplement (Sciencell Research Laboratories, USA, Lot.No.20540)；
100 × penicillin/streptomycin (Sciencell Research Laboratories, USA, Lot.No.21668)；
0.25%EDTA pancreatin (Sciencell Research Laboratories, USA, Lot.No.18105；
Phosphate buffer (PBS, 0.0.1M, PH7.4, green skies Bioisystech Co., Ltd,
Lot.No.061716160629)；
Cell counting Kit (Cell counting kit, CCK-8) (eastern Renhua subject skill (Shanghai) Co., Ltd.,
USA, Lot.No.KR674)；
Human umbilical vein endothelial cells (HUVEC) (Sciencell Research Laboratories, USA,
Lot.No.11234)；
Resveratrol: Sigma-Aldrich (Shanghai) trade Co., Ltd, Lot.No.SLBL1881V；
High-temp steam sterilizing pot, electrical machinery of Japanese sanyo company, MLS-3750；
Air dry oven, the upper macro experimental facilities Co., Ltd of Nereid, DHG-9053A；
Superclean bench, ESCO Corporation, ACB-4A1；
Cell incubator, electrical machinery of Japanese sanyo company, MCO-15AC；
Centrifuge, Shanghai Medical Appliance (Group) Co., Ltd. Surgical Instruments Factory, 0406-1；
Microscope, Olympus (China)Co., Ltd., CKX31SF-5；
Microplate reader, U.S. paddy molecule instrument (Shanghai) Co., Ltd., VESRAmax；
Electronic balance, Mei Tele-support benefit international trade (Shanghai) Co., Ltd., MS204S；
- 80 DEG C of low temperature refrigerators, New Brunswick Scientific Co., Inc, Premium U410；
Nuclear Magnetic Resonance: Switzerland BrukerAVANCE III 600MHz (MA, USA).
The preparation of 1 type I compound of embodiment
Separation prepares type I compound from masson pine fresh pine needle with the following method:
(1) the fresh pine needle 250kg of masson pine is added in 4 times of amount boiling water, refluxing extraction 1h, filtering, and 3 times of amounts are added again
Water, refluxing extraction 1 hour, medicinal extract 21.59kg was concentrated under reduced pressure to obtain in filtering, merging filtrate, spare；
(2) take medicinal extract 7.82kg obtained in step (1), it is water-dispersible after in batches loading to macroreticular resin D101, then according to
It is secondary to use water, 20% ethanol elution, 3 times of column volumes, 20% ethanol elution part is collected, eluate a (668g) is concentrated and dried to obtain, it is standby
With；
(3) after the eluate a of step (2) being dissolved with water loading MCI column chromatograph, successively pass through water, 10% ethanol elution,
10% ethanol eluate is collected, eluate b (257g) is concentrated and dried to obtain, it is spare；
(4) after the eluate b of step (3) being dissolved with water loading ODS column chromatograph, successively pass through water, 10% ethanol elution,
10% ethanol eluate is collected, eluate c (143g) is concentrated and dried to obtain, it is spare；
(5) after dissolving the eluate c of step (4) with 20% ethyl alcohol, sephadex LH-20 column chromatography for separation is carried out,
20% elution, collects the 3rd~4 times of column volume eluent, is concentrated and dried to obtain eluate d (53g), spare；
(6) loading YMC column chromatographs after dissolving the eluate d of step (5) with water, is successively washed respectively with 2%, 5% ethyl alcohol
3 times of column volumes are taken off, 5% ethanol elution part is collected, is concentrated and dried to obtain eluate e (13g), it is spare.
(7) loading sephadex LH-20 column chromatography for separation after dissolving eluate e in step (6) with 30% ethyl alcohol,
30% ethanol elution collects the 3rd times of column volume, is concentrated and dried to obtain eluate f (1.8g), spare.
(8) by eluate f CH in step (7)2Cl2: loading silica gel column chromatography point after 95% ethyl alcohol (4:1, v/v) dissolution
From EtOAc:95% ethyl alcohol (6:1, v/v) elution, by eluent point silica gel thin-layer plate, with EtOAc:95% ethyl alcohol (4:1, v/v)
It is analyzed as solvent, collects the eluent for showing principal spot on lamellae, be concentrated and dried to obtain eluate g.
(9) by eluate g CH in step (8)2Cl2: loading silica gel column chromatography point after 95% ethyl alcohol (4:1, v/v) dissolution
From through CH2Cl2: 95% ethyl alcohol (4:1, v/v) elution by eluent point silica gel thin-layer plate, uses CH2Cl2: 95% ethyl alcohol (4:1,
V/v it) is analyzed as solvent, collects the eluent for showing single spot on lamellae, concentrate drying obtains type I compound
240mg。
2 type I compound Structural Identification of embodiment
5mg type I compound is weighed, is dissolved with 0.5mL deuterated methanol, nuclear magnetic tube, measurement are packed into1H-NMR (600MHz) spectrum.
25mg type I compound is weighed, is dissolved with 0.5mL deuterated methanol, nuclear magnetic tube, measurement 13C-NMR (150MHz) spectrum are packed into.As a result such as
Under:
1H-NMR (600MHz, CD3OD): 6.89 (1H, d, J=9.0Hz, H-5), 6.80 (1H, d, J=2.4Hz, H-2),
6.70 (1H, dd, J=9.0,2.4Hz, H-6), 5.00 (1H, d, J=2.4Hz, H-1 "), 4.77 (1H, d, J=7.2Hz, H-
A), 1H, dd, J=10.8,1.8Hz, H-6 ' a), 4.04 1 ') (3.98 (1H, d, J=9.6Hz, H-4 " 3.93 (1H, d, J=
2.4Hz, H-2 "), 3.83 (3H, s, OMe-3), 3.80 (3H, s, OMe-4), b), 3.77 (1H, d, J=9.6Hz, H-4 " 3.62
(1H, m, H-6 ' b), 3.59 (2H, s, H-5 "), 3.57 (1H, dd, J=6.6,1.8Hz, H-3 '), 3.45 (2H, m, H-2 ',
5′),3.35(1H,m,H-4′).13C-NMR(150MHz,CD3OD):153.8(C-1),151.1(C-3),146.2(C-4),
114.1(C-5),111.0(C-1″),109.5(C-6),104.4(C-2),103.5(C-1′),80.5(C-3″),78.0(C-
3′),77.9(C-5′),77.0(C-2″),75.0(C-4″),74.9(C-2′),71.7(C-4′),68.8(C-6′),65.6(C-
5 "), 57.2 (OMe-4), 56.6 (OMe-3) compounds are white powder, are soluble in ethyl alcohol.Above data and document
(Bioactive drimane sesquiterpenoids and aromatic glycosides,Bioorganic&
Medicinal Chemistry Letters, 2017,27,1754-1759) report is consistent, therefore identify that the compound is 3,4-
dimethoxyphenyl-1-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside.
3 type I compound anti-oxidative damage activity research of embodiment
3.1 cell culture and passage
The HUVEC cell newly bought is defined as 0 generation cell, is cultivated the cells using 5%FBS culture medium, culture medium
Configuration process are as follows: be added to 25mL fetal calf serum, 5mL endothelial cell growth supplement and 5mL penicillin/streptomycin solution
In 500mL Endothelial cell culture base, mixing be can be used.
When cell confluency reaches 80%, cell is passed on: first by 5%FBS culture medium and pancreatin from 4 DEG C of ice
Case is taken out, and preheats in 37 DEG C of water-baths, after be transferred on aseptic operating platform.Then cell bottle is taken out from incubator and is placed in
The operation of digestion step is carried out on station: culture medium in bottle is poured out, and is drawn 5mLPBS and is added in culture bottle, vibrates body
Cell is washed, then pours into PBS in waste liquid bottle.It then draws 2mL0.25%EDTA pancreatin to be placed in culture bottle, jog body
Enable pancreatin to cover whole cells, culture bottle is then placed in microscopically observation, obvious, cell occurs to space between cells
After deformation, pancreatin is poured out on station, is rapidly added 10mL5%FBS culture medium, jog body makes culture medium covering complete
Portion's cell.Then cell is blown and beaten using suction pipe, until microscopic observation cell is in individually existing, when piping and druming should be controlled
Good dynamics, in order to avoid damaging cells.
After digestion step, culture medium containing cell is divided into after 2-3 parts according to cell density and is sub-packed in newly
Tissue Culture Flask in.The cell bottle of passage is then put into 37 DEG C, is cultivated in 5%CO2 incubator, avoids culture medium from connecing in the process
The hidden danger that the bottleneck of touching culture bottle pollutes.When the cell confluency in new biography generation reaches 80%, repeat the above steps progress
Passage, point 96 orifice plates carry out activity assays after reaching 4 generation cells.
It is counted after 3.2 cell dissociations
The HUVEC cell that fusion rate reaches 80% is subjected to digestion process first, step is the same as 3.1.To HUVEC cell dissociation
After, it draws on 10 μ L cell suspensions to cell counting board, completes viable count in three minutes.Counting region be 16 ×
25 four, type cell counter edges big angle, total number of cells/4 × 10 at cell number=tetra- angle in 1ml culture medium4。
3.3 cells point, 96 orifice plates
After cell count, cell suspension and 5% culture medium are proportionally mixed so that cell suspension density be 3 ×
104Then a/mL divides 96 orifice plates.Scoreboard requires to be 3000/hole, and volume is 100 holes μ L/.Most peripheral hole when 96 orifice plate scoreboard
It is added without cell, surveys 11 column holes not for PBS to be added to avoid internal holes culture medium Influence of Evaporation cell viability, and there are most right
Cell is added, culture medium is only added as blank group hole.Primary cell passage number is identical as experiment limitation algebra when testing scoreboard,
Therefore the discarding of scoreboard remaining cell does not use.Pharmaceutical intervention experiment is carried out after overnight.
The experiment of 3.4 pharmaceutical interventions
It is blank group, negative group, model group, 500 μ g.mL that cell in 96 orifice plates after staying overnight, which is pressed column split,-1、250μ
g.mL-1、125μg.mL-1Sample sets and 250 μ g.mL-1Resveratrol group (n=6).
1%FBS culture medium and each concentration gradient sample and positive drug solns are configured first:
One, 1%FBS culture medium is configured: by 5mL fetal calf serum, 5mL endothelial cell growth supplement and 5mL penicillin/chain
Mycin solution is added in 500mL Endothelial cell culture base, and mixing can be used；
Two, it configures each concentration gradient sample solution: being 1mg.mL by 0.7mL concentration-1Sample original solution and isometric 1%
After FBS culture medium mixes, obtaining 1.4mL concentration is 500 μ g.mL-1Solution；Solution 0.7mL is then drawn again with 1%
FBS culture medium mixes, and obtaining 1.4mL concentration is 250 μ g.mL-1Solution；0.7mL125 μ is obtained again according to this dilution principle
g.mL-1Sample solution；
Three, positive drug solns are configured: being dissolved the resveratrol of 100mg specification using 0.4mLDMSO, obtaining concentration is
250mg.mL-1Resveratrol original liquid.3 μ L resveratrol original liquids are drawn to be mixed with 1.5mL1%FBS culture medium to get arriving
500μg.mL-1Resveratrol solution, then obtaining 0.7mL concentration according to two-fold dilution's principle is 250 μ g.mL-1Resveratrol
Solution.
Configured drug solution is added in 96 orifice plates according to grouping, while in model group, negative group and blank group
100 μ L 1%FBS Endothelial cell culture bases are added in corresponding aperture, wherein negative group and blank group are respectively as negative control and sky
White control.
The experiment of 3.5 model foundations
After each concentration drug solution acts on cell for 24 hours, the culture medium in model group, drug group hole is sucked out, is added 100
μL400μΜH2O2Solution (dilution of 1%FBS culture medium), blank group and the negative culture medium organized in hole are changed to fresh training simultaneously
It supports base (dilution of 1%FBS culture medium), effect is for 24 hours.
The detection of 3.6 experimental results
6mLCCK-8 solution is obtained after 600 μ L CCK-8 reagents and 5.4mL1%FBS culture medium are mixed, it is then that this is molten
Liquid is added in each group hole in 96 orifice plates, absorbs all culture mediums in hole before being added.After CCK-8 solution effects 4h, in enzyme mark
The OD value in each hole of 96 orifice plates is detected on instrument, then calculates group of cells growth rate.Calculating process is as follows, is grown according to each sample group
Rate (%) evaluates whether the sample has cytoprotection.
Wherein " X " representative model group and sample to be tested group.
Test of many times result is obtained for test is repeated using SPSS17.0 software (SPSS Inc., Chicago, IL, USA)
Statistical analysis is carried out, is indicated with ± S, is compared between each group and examined using t, is indicated with p < 0.05 * or p < 0.01 * * in the presence of system
Meter learns difference.
The experiment of 1 type I compound anti-peroxidation damagine activity of table
P: relative to model group
According to 1 result of table it is found that model group cell growth rate is 60.61%, p value is 0.0003 compared with feminine gender group, tool
There is significant statistical difference, illustrates that cell model is successfully established.The high, medium and low concentration of type I compound is to hydrogen peroxide-induced
Cellular damage has certain inhibiting effect, can be obviously improved cell growth rate, delays or inhibit Apoptosis, has significant
Anti-oxidative damage activity, activity with model group compared with significant statistical significance (p < 0.05, p < 0.01 or p <
0.001).Compared with positive controls (resveratrol 1.096mM), type I compound of the present invention is in significantly lower administration concentration
Comparable antioxidant activity can be generated under (0.279mM), and under substantially comparable administration concentration (1.115mM), formula I
Compound repairs oxidative damage, and the activity for improving cell growth rate is significantly higher than positive controls.As it can be seen that I chemical combination of formula
The cellular damage of hydrogen peroxide-induced can be effectively suppressed in object, improves cell growth rate, has significant anti-oxidative damage activity.
Claims (6)
1. application of a kind of compound in the drug of preparation treatment oxidative damage related disease, wherein the compound has such as
Structure shown in following formula I:
2. application according to claim 1, it is characterised in that the oxidative damage related disease includes: Atherosclerosis
Change, cancer, cataract, age-related macular degeneration.
3. application according to claim 1 or 2, which is characterized in that the type I compound is to extract from natural plants
It obtains to or by chemical synthesis.
4. application according to claim 3, it is characterised in that the type I compound is that the fresh pine needle of masson pine is flowed back with water
After extraction, separation, purifying are obtained.
5. application according to claim 4, it is characterised in that the purification procedures are to soak needles of pinus massoniana extract
Cream passes sequentially through macroreticular resin D101 column chromatography, MCI column chromatography, ODS column chromatography, sephadex LH-20 column chromatography, YMC column layer
Analysis, sephadex LH-20 column chromatography, silica gel column chromatography are isolated and purified.
6. application according to claim 5, it is characterised in that the method isolated and purified comprises the following steps:
(1) it takes the fresh pine needle of masson pine appropriate, adds in 4 times of amount boiling water, refluxing extraction 1h, filter, 3 times of amount water are added again,
Refluxing extraction 1 hour, filtering, medicinal extract was concentrated under reduced pressure to obtain in merging filtrate, spare；
(2) take medicinal extract obtained in step (1), it is water-dispersible after in batches loading then successively use water, 20% to macroreticular resin D101
3 times of column volumes of ethanol elution collect 20% ethanol elution part, are concentrated and dried to obtain eluate a, spare；
(3) loading MCI column chromatographs after dissolving the eluate a of step (2) with water, successively passes through water, 10% ethanol elution.It collects
10% ethanol eluate is concentrated and dried to obtain eluate b, spare；
(4) loading ODS column chromatographs after dissolving the eluate b of step (3) with water, successively passes through water, and 10% ethanol elution is collected
10% ethanol eluate is concentrated and dried to obtain eluate c, spare；
(5) after dissolving the eluate c of step (4) with 20% ethyl alcohol, sephadex LH-20 column chromatography for separation is carried out, 20% washes
It is de-, the 3rd~4 times of column volume eluent is collected, eluate d is concentrated and dried to obtain, it is spare；
(6) loading YMC column chromatographs after dissolving the eluate d of step (5) with water, successively elutes 3 times respectively with 2%, 5% ethyl alcohol
Column volume collects 5% ethanol elution part, is concentrated and dried to obtain eluate e, spare.
(7) loading sephadex LH-20 column chromatography for separation after dissolving eluate e in step (6) with 30% ethyl alcohol, 30% second
Alcohol elution, collects the 3rd times of column volume, is concentrated and dried to obtain eluate f, spare.
(8) by the CH of eluate f volume ratio 4:1 in step (7)2Cl2: loading silica gel column chromatography separates after the dissolution of 95% ethyl alcohol,
The EtOAc:95% ethanol elution of volume ratio 6:1 makees eluent point lamellae with the EtOAc:95% ethyl alcohol of volume ratio 4:1
Solvent is analyzed, and is collected the eluent for showing principal spot on lamellae, is concentrated and dried to obtain eluate g.
(9) by the CH of eluate g volume ratio 4:1 in step (8)2Cl2: loading silica gel column chromatography separates after the dissolution of 95% ethyl alcohol,
CH through volume ratio 4:12Cl2: 95% ethyl alcohol is eluted, by eluent point lamellae, with the CH of volume ratio 4:12Cl2: 95%
Ethyl alcohol is analyzed as solvent, collects the eluent that single spot is shown on lamellae, and concentrate drying obtains I chemical combination of formula
Object.
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