CN106083788A - A kind of quinoid chalcone carbon glycosides dimer compound with anti-tumor activity and anti-inflammatory activity and preparation method thereof - Google Patents
A kind of quinoid chalcone carbon glycosides dimer compound with anti-tumor activity and anti-inflammatory activity and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a kind of quinoid chalcone carbon glycosides dimer compound with anti-tumor activity and anti-inflammatory activity and preparation method thereof.The present invention is by carrying out system further investigation to Flos Carthami chemical composition, one noval chemical compound (formula II) of isolated from Flos Carthami is shown through wave spectrum and MASS SPECTRAL DATA ANALYSIS, the quinoid chalcone carbon glycosides dimer compound that quinone ring is 1,5 cyclohexadienones for isolated first.Show through antiinflammatory and antitumor activity, the quinoid chalcone carbon glycosides dimer compound that the present invention provides has good anti-inflammatory activity, and DNA topoisomerase I can be suppressed, kinds of tumors is respectively provided with the strongest anti-tumor activity, and show through toxicity test research, the quinoid chalcone with anti-tumor activity and anti-inflammatory activity that the present invention provides is relatively low with flavonol conjugate toxicity, can be developed into new antitumor drug or anti-inflammatory drug, has important using value.
Description
Technical field
The present invention relates to the compound with anti-tumor activity, be specifically related to from Chinese medicine safflower extract obtain have
The quinoid chalcone carbon glycosides dimer compound noval chemical compound of anti-tumor activity and anti-inflammatory activity and in prevention and treatment tumor
Purposes in disease and inflammation disease, belongs to pharmaceutical technology field.
Background technology
Flos Carthami is the dry flower of feverfew Flos Carthami Carthamus tinctorius L., begins to be loaded in " Kaibao Bencao ", main
Originating in the ground such as Xinjiang, Henan, Zhejiang, Yunnan, acrid in the mouth is bitter, and GUIXIN, Liver Channel have effect of promoting blood circulation to restore menstrual flow, eliminating stasis to stop pain, makees
For tradition blood-activating and stasis-removing treatment apoplexy, coronary heart disease and the angina pectoris history of existing more than 2500 year.Safflower extracts is made
Flos Carthami injection records in the Sanitation Ministry medicine standard Traditional Chinese medicine historical preparation 20, is widely used in cardiovascular disease clinically
Treatment.At present isolated 200 multiple compounds from Flos Carthami the most, including quinoid chalcone glycoside, flavonoid, alkaloids,
Organic acid and steroid etc., and quinoid chalcone glycoside is the main component of Safflower extracts, such as S-A Hydroxysafflor yellow A
(HSYA), safflower yellow A, safflomin C and dehydration Safflomin B (AHSYB).Modern pharmacological research finds, Flos Carthami
And active component have anticoagulation, antioxidation, antiinflammatory, protect the liver, blood pressure lowering isoreactivity.
The present invention continues to further investigate, Flos Carthami chemical composition system to the quinoid chalcone glycosides compound in water position
Carry out system separation, research and develop its new active structure.
Summary of the invention
Goal of the invention: it is an object of the invention on the basis of prior art, deeply grinds Flos Carthami chemical composition system
Study carefully, the quinoid chalcone glycosides compound in water position is carried out system separation, the active structure that research and development make new advances, and passes through
Pharmacological evaluation screens its new application in preventing and treating tumor disease, inflammation disease and anti embolus disease.
Technical scheme: in order to realize object above, the technical scheme that the present invention takes is:
There is the quinoid chalcone carbon glycosides dimer compound of anti-tumor activity and anti-inflammatory activity, its structural formula such as formula II institute
Show:
There is the preparation method of the quinoid chalcone carbon glycosides dimer compound of anti-tumor activity and anti-inflammatory activity, including with
Lower step:
(1) take Flos Carthami, add ethanol extraction and obtain ethanol extract, united extraction liquid, concentrate, obtain ethanol extract；
(2) take the ethanol extract that step (1) prepares, extract by petroleum ether, ethyl acetate and water successively, dense after extraction
Contracting, respectively obtains the extract of petroleum ether, ethyl acetate and water；
(3) take the extract of the water that step (2) obtains, upper macroporous adsorptive resins, first wash with water, use body the most respectively
Volume concentrations is the ethanol elution of 5～95%, and collected volume concentration is the ethanol elution of 30%, concentrates, obtains macroporous adsorbent resin
Eluate；
(4) taking LH-20 gel filtration chromatography in the macroporous adsorbent resin eluate that step (3) obtains, eluent is H2O-
(volume ratio is from 100: 0 to 0 to MeOH: 100), obtains 30 flow points；
(5) taking step (4) LH-20 gel column eluate, upper pre-HPLC chromatograph separates, and obtains the quinone shown in formula II
Formula chalcone carbon glycosides dimer compound.
Preferably, more than there is the quinoid chalcone carbon glycosides dimer compound of anti-tumor activity and anti-inflammatory activity
Preparation method, the extracting method of step (1) is percolation, ultrasonic extraction, infusion method or circumfluence method.
Preferably, the above-described quinoid chalcone carbon glycosides dimer with anti-tumor activity and anti-inflammatory activity
The preparation method of compound, the separation condition of step (5) pre-HPLC chromatographic isolation: XBridgeTM C18OBDTMPost (150 ×
30mm, 5 μm), flowing is 0.1% formic acid water (A) and methanol (B) mutually, employing gradient elution program: 0-5min, 16%-19%B；
5-15min, 19%B；15-20min, 19%-44%B；20-30min, 44%B；30-32min, 44%-100%B.Flow velocity is
15mL/min；Column temperature is room temperature (25 DEG C).
Of the present invention have the quinoid chalcone carbon glycosides dimer compound of anti-tumor activity and anti-inflammatory activity in system
Application in standby anti-inflammatory drug.
As another preferred version, the quinoid chalcone carbon glycosides with anti-tumor activity and anti-inflammatory activity of the present invention
Dimer compound application in preparing resisting thrombotic diseases.
As another preferred version, the quinoid chalcone carbon glycosides with anti-tumor activity and anti-inflammatory activity of the present invention
Dimer compound application in preparing antitumor drug.Described tumor is pulmonary carcinoma, gastric cancer, colon cancer, cervical cancer, mammary gland
Cancer, hepatocarcinoma or renal carcinoma.
The quinoid chalcone carbon glycosides dimer compound with anti-tumor activity and anti-inflammatory activity of the present invention, by quinone
Formula chalcone carbon glycosides dimer compound compound and pharmaceutically acceptable carrier are prepared as tablet, capsule, injection, powder
Injection, granule, microcapsule, pill, ointment or the medicine of skin-permeable and control-released plaster dosage form.
When the quinoid chalcone carbon glycosides dimer compound that the present invention provides is made tablet, quinoid chalcone carbon glycosides two
Dimmer compound and lactose or corn starch, add magnesium stearate lubricant, mix homogeneously, granulate, then tabletting system when needing
Piece agent.
Quinoid chalcone carbon glycosides two when the quinoid chalcone carbon glycosides dimer compound that the present invention provides makes capsule
Dimmer compound and carrier lactose or corn starch mix homogeneously, granulate, the most encapsulated make capsule.
When the quinoid chalcone carbon glycosides dimer compound that the present invention provides makes granule, quinoid chalcone carbon glycosides two
Dimmer compound and diluent lactose or corn starch, mix homogeneously, granulate, it is dried, makes granule.
The quinoid chalcone carbon glycosides dimer compound that the present invention provides adds carrier by medicine when making injectable powder, injection
Conventional method prepares.
The quinoid chalcone carbon glycosides dimer compound that the present invention provides makes lipomul, ointment or percutaneous controlled-release patch
Add carrier during the dosage forms such as agent to prepare by pharmacy conventional method.
Beneficial effect: the quinoid chalcone carbon glycosides with anti-tumor activity and anti-inflammatory activity that the present invention provides is Dimerized
Compared to the prior art compound has the advantage that
The present invention by Flos Carthami chemical composition is carried out system further investigation, through wave spectrum and MASS SPECTRAL DATA ANALYSIS show from
Isolated chalcone compounds in Flos Carthami, the compound shown in formula II be the quinone ring of isolated first be 1,5-hexamethylene two
The quinoid chalcone carbon glycosides dimer of ketenes, is all new framework structured compound.And through antiinflammatory and antitumor activity table
Bright, the quinoid chalcone carbon glycosides dimer compound that the present invention provides has good anti-inflammatory activity, and can suppress DNA topology
Isomerase I, is respectively provided with the strongest anti-tumor activity, and shows through toxicity test research kinds of tumors, and the present invention provides
The quinoid chalcone carbon glycosides dimer compound toxicity with anti-tumor activity and anti-inflammatory activity is relatively low, can be developed into new resisting and swells
Tumor medicine or anti-inflammatory drug, have important using value.
The preparation method that the present invention provides, technological design is reasonable, workable, the quinoid chalcone carbon glycosides prepared
Dimer compound purity is high.
Accompanying drawing explanation
Fig. 1 is the structural representation of quinoid chalcone carbon glycosides dimer compound formula II；
Fig. 2 is quinoid chalcone carbon glycosides dimer compound formula II1H-NMR schemes；
Fig. 3 is quinoid chalcone carbon glycosides dimer compound formula II13C NMR schemes.
Detailed description of the invention
According to following embodiment, the present invention be may be better understood.But, as it will be easily appreciated by one skilled in the art that reality
Execute concrete material proportion, process conditions and result thereof described by example and be merely to illustrate the present invention, and should also will not limit
The present invention described in detail in claims processed.
The preparation of embodiment 1 quinoid chalcone carbon glycosides dimer compound
There is the preparation method of the quinoid chalcone carbon glycosides dimer compound of anti-tumor activity and anti-inflammatory activity, including with
Lower step:
(1) take Flos Carthami 15kg, be sequentially added into the ethanol percolate extraction that volumetric concentration is 95% and 70% the most colourless, obtain second
Alcohol extract, united extraction liquid, concentrate, obtain ethanol extract 1950g；
(2) take the ethanol extract that step (1) prepares, be dispersed in water, extract by petroleum ether and ethyl acetate successively,
Concentrate after extraction, respectively obtain the extract of petroleum ether, ethyl acetate and water；
(3) take the extract of the water that step (2) obtains, upper D101 macroporous adsorptive resins, first wash with water, then distinguish
With the ethanol elution that volumetric concentration is 5～95%, collected volume concentration is the ethanol elution of 30%, concentrates, obtains macroporous absorption
Resin eluate；
(4) taking LH-20 gel filtration chromatography in the macroporous adsorbent resin eluate that step (3) obtains, eluent is H2O-
(volume ratio is from 100: 0 to 0 to MeOH: 100), obtains 30 flow points；
(5) taking step (4) LH-20 gel column eluted fraction the 9th flow point and the 3rd flow point, upper pre-HPLC chromatograph is carried out point
From, the separation condition of pre-HPLC chromatographic isolation: XBridgeTM C18OBDTMPost (150 × 30mm, 5 μm), flowing is mutually
0.1% formic acid water (A) and methanol (B), employing gradient elution program: 0-5min, 16%-19%B；5-15min, 19%B；15-
20min, 19%-44%B；20-30min, 44%B；30-32min, 44%-100%B.Flow velocity is 15mL/min；Column temperature is room
Temperature (25 DEG C).
Obtain the quinoid chalcone carbon glycosides dimer compound shown in formula II, structural formula such as Fig. 1.
Shown in formula II:
Formula II structure elucidation is: dark orange powder, [α]D 20:+134.7(c 0.1,MeOH).High resolution mass spectrum (HR-ESI-
MS:m/z=1043.2679 [M-H]-1, calcd.1043.2674) and show that its molecular formula is C48H51O26.Infrared spectrum exists
3433cm-1Place strong absorb display it with the presence of hydroxyl, at 1640cm-1Also there is the characteristic absorption of carbonyl in place, simultaneously 1513
And 1400cm-1Also there is the characteristic absorption of aromatic ring in place.Ultraviolet spectra shows that 228,344 and 420nm have absorption maximum, and molecule is described
Middle existence height conjugated system.
1H-NMR (Fig. 2) show two sets hydroxyl cinnamyl signal is respectively δ 7.51 (1H, d, J=16.0Hz), 7.19
(1H, d, J=16.0Hz), 7.39 (2H, d, J=8.5Hz), 6.76 (2H, d, J=8.5Hz), 9.70 (1H, br s), and δ
7.45 (1H, d, J=16.0Hz), 7.16 (1H, d, J=16.0Hz), 7.37 (2H, d, J=8.5Hz), 6.76 (2H, d, J=
8.5Hz).Additionally,1H-NMR also has two carbon glycosides glucose terminal hydrogen signal δ 3.78 (1H, d, J=9.0Hz) and 3.57
(1H, d, J=9.5Hz), deoxysorbitol terminal hydrogen signal δ 4.56 (1H, d, J=8.0Hz), and some glycosyl hydrogen letter
Number δ 2.9-4.6ppm.
13C-NMR (Fig. 3) shows 48 carbon atoms, in conjunction with1H-NMR, HSQC and accurate molecular weight, can determine that this chemical combination
Thing is the isomers of AHSYB.Equally, on MS/MS spectrogram, the cracking of this compound produces m/z 1025.25 [M-H-
H2O]-、923.22[M-H-C8H8O]-、593.15[M-H-C21H22O11]-With 449.11 [M-H-C27H30O15]-, crack with AHSYB
Fragments characteristic consistent.
At HMBC spectrally, H-2 " " is relevant with C-1 shows that OH-2 " " and C-1 phenolic hydroxyl group form ester bond.Phenolic hydroxyl group hydrogen signal
δ 18.31 and C-1 ' (181.5), C-2 ' (106.0) and C-6 ' (101.4) HMBC are relevant shows that this compound is with 1-enol-3,7-
Diketone form exists.Two quinone rings of this compound all exist with 1,5-cyclohexadienone form.
Compound presents negative cotton effect at 272nm, shows that the absolute configuration of 4 and 4 ' is S.Close according to source of students
One-tenth approach, anhydro sorbitol is derived by D-Glucose, and the coupling constant in conjunction with its anomeric proton is 8.0Hz, anhydrosorbitol
Alcohol is defined as 1-and is dehydrated D-glucitol, and the absolute configuration of 1 " " is S.
The screening active ingredients that the HUVEC cellular inflammation that embodiment 2 suppresses LPS to induce is reacted
The essence of syndrome of blood stasis is microcirculation disturbance or hemorheology sexual abnormality.Along with cell, molecular biology research deep
Entering, inflammatory reaction is close with Relationship of Blood Stasis Syndrome, and a series of inflammatory cell and inflammatory factor participate in the lysis of syndrome of blood stasis.Therefore
This experiment uses LPS induction HUVEC to set up cell in vitro inflammatory response model and evaluates the antiinflammatory of quinoid chalcone glycosides compound
Activity.
1, experiment material
1.1 instrument
SERIES IIWATERJAVKET type CO2Incubator (Thermo company of the U.S.)；1300SERIES A2 type biology is pacified
Full cabinet (Thermo company of the U.S.)；BWS-10 type water-bath (Kunshan Yiheng Scientific Instruments Co., Ltd)；TOMY SX-500 high steam
Autoclave (Queensland company of Japan)；EPED ultrapure water system (Nanjing Yi Puyida development in science and technology company limited)；
CKX31SF type inverted microscope (OLYMPUS company)；(U.S. BECKMAN is public for Allegra X-12R common bench centrifuge
Department)；6 well culture plates (Costar company of the U.S.)；WGL-230B type electric drying oven with forced convection (the Tianjin limited public affairs of Stettlen instrument
Department)；QPCR instrument (Applied Biosystem company of the U.S.)；(Japan Queensland is public for ultramicron nucleic acid-protein detector
Department).
1.2 cells and reagent
HUVEC cell is purchased from Nanjing KaiJi Biology Science Development Co., Ltd；High sugar DEME culture medium and hyclone
(FBS) purchased from Gibco company of the U.S.；Lipopolysaccharide (LPS) is purchased from Sigma-Aldrich；TRIzol reagent is purchased from
American I nvitrogen company；PrimeScriptTMRT reagent kit is purchased from DaLian, China TaKaRa company.
2, experimental technique
2.1 cells are cultivated
HUVEC cell is incubated at the hyclone containing 10%, 100mg mL-1Penicillin, 100mg mL-1Streptomycin
In DMEM culture medium, it is placed in 37 DEG C, in 5% CO2 gas incubator.2～3d change culture fluid, and 3～4d pass on once.
2.2 cells process and packet
By HUVEC cell by 1 × 105Individual mL-1It is inoculated in six orifice plates, the full volume 2mL in every hole.Experiment is divided into 3 groups: blank
Group, is added without LPS and medicine；Model group, adds LPS, final concentration 10 μ g mL-1, it is not added with medicine；Administration group: be sequentially added into
Upper formula II compound, making formula formula II-1 compound concentration is 0.8 μm ol L-1, formula II-2 compound concentration be 4 μm ol L-1、
Formula II-3 compound concentration is 20 μm ol L-1, II-4 compound concentration be 100 μm ol L-1Medicine.Successive administration was received after 2 days
Collection cell, is used for extracting total serum IgE.
2.3RNA extract
Respectively adding 500 μ L RNAzol in the 6 each holes of orifice plate, prepare 1.5mL sub warhead, the good mark of labelling, with scraper by thin
In the EP pipe of what born of the same parents HUVEC was careful scrape and transfer to 1.5mL；Add 500 μ L DEPC H2O, suspendible 15s；Centrifugal
(13200rpm, 10min, 4 DEG C)；Take supernatant 1000 μ L in new EP pipe, centrifugal (13200rpm, 30min, 4 DEG C)；Observe
RNA form, pours out supernatant liquid, adds 500 μ L 70% ethanol in each EP pipe, centrifugal (13200rpm, 10min, 4 DEG C)；
It is repeated 1 times, is inverted, after drying, each addition 55 DEG C of DEPC H of 20 μ L2O ,-80 DEG C of preservations；Nano drop measures rna content
(scope of A260/280 is at 1.8-2.0).
2.4 turns of cDNA
TaKaRa test kit: PrimeScriptTMRT reagent Kit with gDNA Eraser
1) genomic DNA removes reaction
2) reverse transcription reaction
Store at 4℃；
3) Nano drop measures cDNA content (scope of A260/280 is at 1.6-1.8).
2.6. 1.2.5qRT-PCR SYBR Green test kit (QIAGEN)
1) qPCR reaction system preparation
2) qPCR response procedures is arranged
Take the logarithm trophophase HUVEC, adds finite concentration medicine effect, utilizes RNAzol one-step method to extract total serum IgE, 1 μ g
Total serum IgE carry out reverse transcription with 10 μ L systems, preparation cDNA reverse transcriptional PCR.Use primer is as follows:
3, experimental result
The HUVEC cellular inflammation factor expression result of table 1 formula II quinoid chalcone glycoside compound suppression LPS induction
Compared with blank group,#P < 0.05,##P < 0.01, compared with model group, * P < 0.05, * * P < 0.01.
Be test result indicate that by above table 1, formula II quinoid chalcone carbon glycosides dimer compound significantly raises anti-inflammatory factors
The gene expression effect of IL-10, formula II quinoid chalcone carbon glycosides dimer compound can suppress IL-1, IL-6 according to patience by dosage
With the gene expression of IFN-γ, formula II quinoid chalcone carbon glycosides dimer compound only base to TNF-α under high dose concentration
Having, because expressing, the effect of significantly inhibiting, further demonstrate that, quinoid chalcone carbon glycosides dimer compound has specific antiinflammatory
Activity, has the potentiality being developed into a new generation's anti-inflammatory agent.
Embodiment 3 suppresses the screening active ingredients of DNA topoisomerase I
DNA topoisomerase (Topoisomerase) is a kind of important ribozyme, participate in DNA replication dna, transcribe, recombinate,
The important vital movement such as Gene regulation and cell mitogen, can control its topology knot by catalytic dna chain break and combination
Structure.In tumor cell, Topo I content and activity, far above normal somatic cell, suppress Topo I-DNA cleavable complex solution
From, the just fast breeding of energy Selective depression tumor cell, and then kill tumor cell[8].Topo I thus becomes generally acknowledged resisting
Cancer medicine action target spot.Therefore this experiment uses the model evaluation quinoid chalcone carbon glycosides dimer chemical combination of vitro inhibition DNA Topo I
The anti-tumor activity of thing.
1, experiment material
1.1 instrument
Gel imaging instrument (Shanghai Peiqing Science Co., Ltd), electrophresis apparatus (Beijing Liuyi Instrument Factory), metal bath (Hangzhou
Bo Science and Technology Ltd.).
1.2 medicines and reagent
DNA Topo I、ρBR322DNA、Agarose Regular、6×Loading Buffer、Tris-Borate-
EDTA Buffer (TBE) powder is purchased from precious biological (Dalian) company limited；10-hydroxycamptothecine (OPT) and dodecyl
Sodium sulfate is purchased from Shanghai Aladdin biochemical technology company；Super green I is purchased from Beijing Fanbo Biochemicals Co., Ltd..Real
Execute the formula II quinoid chalcone carbon glycosides dimer compound that example 1 prepares.
2, experimental technique
This test uses 20 μ L reaction systems, including 10 × Topo I buffer (350mM Tris-HCl pH 8.0,
720mM KCI, 50mM MgCl2, 50mM DTT, 50mM spermidine), 0.1%BSA, 0.5 μ g calf thymus ρ
BR322DNA, 1U Topo I, the DMSO solution of testing compound, positive drug is 10-hydroxycamptothecine (OPT).It is placed in 37 DEG C of gold
Belong to and bath is reacted 30min, add 5 μ L reaction terminating liquid 1.5% sodium lauryl sulphate (SDS) and terminate reaction.1 μ L product and 2 μ
L 6 × loading buffer mixes loading, 1% agarose gel, tbe buffer liquid, 90V voltage, electrophoresis 60min.Sybr
Green I dyes 30min, gel imaging instrument observed result, Taking Pictures recording.Enzyme activity unit defines: can be 37 DEG C of 30min pines
Speed the Topo I enzyme amount needed for 0.5 μ g negative supercoiling ρ BR322DNA, be 1 unit (U).
3, experimental result
Topo I is had obvious inhibiting effect, result to show quinoid chalcone carbon glycosides dimerization by formula II compound when 100 μMs
Body has preferable anti-tumor activity.
Embodiment 4 anticancer experiment in vitro
The present invention uses the formula II quinoid chalcone carbon glycosides dimer that the embodiment of the present invention 1 is prepared by improvement mtt assay
Compound carries out extracorporeal anti-tumor cell experiment: by pulmonary carcinoma, gastric cancer, colon cancer, cervical cancer, breast carcinoma, hepatocarcinoma or renal carcinoma pancreas
It is 5 × 10 that enzyme carries out digesting, counting, make concentration4The cell suspension of individual/ml.Hole every in 96 orifice plates is added 100 μ l cells hang
Liquid (every hole 5 × 103Individual cell), it is subsequently placed in 37 DEG C, 5%CO2Incubator is cultivated 24 hours；Dilute by non-fully culture medium
Formula II quinoid chalcone glycoside compound is to required different gradient concentrations, and every hole adds 100 μ L corresponding pastille culture medium, simultaneously
Set up negative control group, Vehicle controls group and positive controls, then 96 orifice plates are placed in 37 DEG C, 5%CO2Incubator is cultivated 72
Hour.Then every hole adds 20 μ L MTT (5mg/ml), continues to cultivate 4 hours, terminates cultivating, discards culture medium, and every hole adds
150 μ L DMSO dissolve, and shaking table mixes for 10 minutes gently.Every hole is detected by microplate reader under λ=4570nm, 620nm two wavelength
Absorbance i.e. OD value, using each meansigma methods in hole of answering as the OD value of this group cell, calculates the suppression ratio of each medicine.
The formula II quinoid chalcone carbon glycosides dimer compound that the experimental result display embodiment of the present invention 1 prepares, right
Pulmonary carcinoma, gastric cancer, colon cancer, cervical cancer, breast carcinoma, hepatocarcinoma or renal carcinoma are respectively provided with stronger inhibitory action, at 10 μ g/ml dosage
Under, pulmonary carcinoma, gastric cancer, colon cancer, cervical cancer, breast carcinoma, hepatocarcinoma or renal carcinoma suppression ratio are all higher than 50%.
Embodiment of above only for technology design and the feature of the present invention are described, its object is to allow and is familiar with technique
People understands present invention and is carried out, and can not limit the scope of the invention with this, all real according to spirit of the present invention
The equivalence that matter is done changes or modifies, and all should contain within the scope of the present invention.
Claims (9)
1. there is the quinoid chalcone carbon glycosides dimer compound of anti-tumor activity and anti-inflammatory activity, it is characterised in that its structure
Formula is as shown in formula II:
2. having the preparation method of the quinoid chalcone carbon glycosides dimer compound of anti-tumor activity and anti-inflammatory activity, its feature exists
In, comprise the following steps:
(1) take Flos Carthami, add ethanol percolate extraction and obtain ethanol extract, united extraction liquid, concentrate, obtain ethanol extract；
(2) take the ethanol extract that step (1) prepares, be dispersed in water, extract by petroleum ether and ethyl acetate successively, extraction
Rear concentration, respectively obtains the extract of petroleum ether, ethyl acetate and water；
(3) take the extract of the water that step (2) obtains, upper macroporous adsorptive resins, first wash with water, dense with volume the most respectively
Degree is the ethanol elution of 5～95%, and collected volume concentration is the ethanol elution of 30%, concentrates, obtains macroporous adsorbent resin eluting
Thing；
(4) taking LH-20 gel filtration chromatography in the macroporous adsorbent resin eluate that step (3) obtains, eluent is H2O-MeOH, body
Long-pending ratio is for, from 100:0 to 0:100, obtaining 30 flow points；
(5) taking step (4) LH-20 gel column eluted fraction, upper pre-HPLC chromatograph separates, and obtains the quinoid shown in formula II
Chalcone carbon glycosides dimer compound.
3. having the preparation method of the quinoid chalcone carbon glycosides dimer compound of anti-tumor activity and anti-inflammatory activity, its feature exists
In, the extracting method of step (1) is percolation, ultrasonic extraction, infusion method or circumfluence method.
4. having the preparation method of the quinoid chalcone carbon glycosides dimer compound of anti-tumor activity and anti-inflammatory activity, its feature exists
In, the separation condition of step (5) pre-HPLC chromatographic isolation: XBridgeTM C18 OBDTMPost, specification is 150 × 30mm, 5 μ
M, mobile phase A be mutually 0.1% formic acid water be methanol with B phase, use gradient elution program: 0-5min, 16%-19%B；5-
15min, 19%B；15-20min, 19%-44%B；20-30min, 44%B；30-32min, 44%-100%B.Flow velocity is
15mL/min；Column temperature is 25 DEG C.
The quinoid chalcone carbon glycosides dimer chemical combination with anti-tumor activity and anti-inflammatory activity the most according to claim 1
Thing, it is characterised in that quinoid chalcone carbon glycosides dimer compound compound and pharmaceutically acceptable carrier are prepared in flakes
Agent, capsule, injection, injectable powder, granule, microcapsule, pill, ointment or the medicine of skin-permeable and control-released plaster dosage form.
6. the quinoid chalcone carbon glycosides dimer compound with anti-tumor activity and anti-inflammatory activity described in claim 1 is in system
Application in standby anti-inflammatory drug.
7. the quinoid chalcone carbon glycosides dimer compound with anti-tumor activity and anti-inflammatory activity described in claim 1 is in system
Application in standby resisting thrombotic diseases.
8. the quinoid chalcone carbon glycosides dimer compound with anti-tumor activity and anti-inflammatory activity described in claim 1 is in system
Application in standby antitumor drug.
The quinoid chalcone carbon glycosides dimer compound with anti-tumor activity and anti-inflammatory activity the most according to claim 8
Application in preparing antitumor drug, it is characterised in that described tumor is pulmonary carcinoma, gastric cancer, colon cancer, cervical cancer, mammary gland
Cancer, hepatocarcinoma or renal carcinoma.
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| PCT/CN2016/098655 WO2017219510A1 (en) | 2016-06-24 | 2016-09-12 | Quinoid chalcone c-glycoside dimer compound having anti-tumor activity and anti-inflammatory activity and method for preparing same |
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| CN108743602A (en) * | 2018-08-27 | 2018-11-06 | 滨州医学院 | Sydroxy carthamin B is preparing the application in treating breast cancer medicines |
| CN109602737A (en) * | 2019-01-25 | 2019-04-12 | 滨州医学院 | Application and drug of the Sydroxy carthamin B in preparation treatment gastric cancer medicament |
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| CN111362896B (en) * | 2018-12-25 | 2022-10-04 | 浙江永宁药业股份有限公司 | Safflower yellow and its application in preparing medicine for treating cardiovascular and cerebrovascular diseases |
| CN114199974B (en) * | 2021-09-30 | 2022-08-05 | 南开大学 | Screening method of specific binding target protein based on isomer |
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| CN108743602A (en) * | 2018-08-27 | 2018-11-06 | 滨州医学院 | Sydroxy carthamin B is preparing the application in treating breast cancer medicines |
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| CN109602737A (en) * | 2019-01-25 | 2019-04-12 | 滨州医学院 | Application and drug of the Sydroxy carthamin B in preparation treatment gastric cancer medicament |
| CN109602737B (en) * | 2019-01-25 | 2021-02-19 | 滨州医学院 | Application of hydroxysafflor yellow B in preparation of medicine for treating gastric cancer and medicine |
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| CN106083788B (en) | 2018-06-19 |
| WO2017219510A1 (en) | 2017-12-28 |
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