CN103435550B - Tanshinone derivative, preparation method and application thereof - Google Patents
Tanshinone derivative, preparation method and application thereof Download PDFInfo
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- CN103435550B CN103435550B CN201310245320.9A CN201310245320A CN103435550B CN 103435550 B CN103435550 B CN 103435550B CN 201310245320 A CN201310245320 A CN 201310245320A CN 103435550 B CN103435550 B CN 103435550B
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Abstract
The present invention relates to a tanshinone derivative, a preparation method and an application thereof. The tanshinone derivative preparation method comprises: dissolving the total tanshinone effective fraction, benzaldehyde and ammonium acetate in ethanol, carrying out a stirring reaction at a temperature of 20-90 DEG C, taking the reactant, extracting to obtain the total tanshinone reactant dry extract, and purifying the reactant dry extract to obtain the tanshinone derivative. The present invention further discloses an application of the tanshinone derivative in preparation of angiogenesis promotion drugs and anti-tumor drugs. According to the present invention, the tanshinone derivative is provided, can be provided for treating ischemic cerebrovascular diseases, and had characteristics of rapid effect and safe medication; and the tanshinone derivative can be used for preparing treatment drugs of blood supply improvement and ischemic tissue rescue through angiogenesis, and preparing anti-lung cancer treatment drugs and other tumor disease treatment drugs.
Description
Technical field
The present invention relates to a kind of tanshinone derivative, be specially a kind of tanshinone derivative and its preparation method and application.
Background technology
Vasculogenesis (angiogenesis) is on original vasoganglion basis, goes out to form little angiogenic growth and the side Zhi Xunhuan of surrounding tissue by stimulating endothelial cell bud, generates the complex process of new vessel.This process relates to the degraded of vascular endothelial cell epimatrix, endotheliocyte to multiple steps such as the migration of substrate degradation place, propagation, stretching, extension and tubular structure formation and the generations of endotheliocyte epimatrix film, mainly comprises: the degraded of active period basement membrane of blood vessel; The activation of vascular endothelial cell, propagation, migration; Rebuilding and form new blood vessel and vasoganglion, is a complex process that relates to various kinds of cell and different kinds of molecules.Vascularization is the complex process of short angiogenesis factor and supressor coordinative role, and the two,, in equilibrium state, will activate vascular system once this balance is broken under normal circumstances, makes vasculogenesis transition or suppress vascular system blood vessel is degenerated.
Vasculogenesis refers to that endotheliocyte germinates and forms new blood vessel from existing blood vessel.Its forming process is very complicated, and is the very important phenomenon of one of observing in all respects of life entity, for example the vasculogenesis of growth and growth, pathologic vessels generation (growth of for example tumour, diabetic retinopathy) etc.Conventional angiogenic factor is mainly vascular endothelial growth factor (VEGF), fiber mother cell growth factor (FGF), angiogenesis factor ((Ang-1) etc.They have coordination, complementary effect in angiogenic process.VEGF is the specificity mitogen of endotheliocyte, it can by with the acceptor VEGF-Rl of endothelial cell surface, VEGF-R2 specific binding, the migration of mediation endotheliocyte, propagation are to build the cavity configuration of blood vessel.FG-1 and FGF-2, respectively at endotheliocyte, smooth muscle cell and Fibroblast acceptor FGFR-1 and FGFR-2 combination, are playing an important role aspect vasostimulant new life and increase blood vessel strength and toughness.Ang-1 is by after being combined with its specific receptors Tie, and mediation vascular endothelial cell and around sustenticular cell participate in the reconstruction of later stage blood vessel, and at protection new vessel, treatment of vascular seepage aspect plays active effect.
The most frequently used in current Therapeutic angiogenesis method is gene therapy and the recombinant protein treatment of exogenous Angiogensis somatomedin (as VEGF or Ang), but Angiogensis somatomedin therapeutic transgene exists immunogenicity, regulation and control difficulty; There is the aberrant angiogenesis growth whether other positions occur, even tumorigenic risk in Angiogensis somatomedin recombinant protein intravenously administrable; Exogenous Angiogensis somatomedin because of the transformation period short, be difficult to, by hemato encephalic barrier, repetitively administered, be prone to the problems such as side effect, limited its application.
When various ischemic cardiovascular due to unstable angina pectoris, acute myocardial infarction, coronary stenosis, AS, thrombosis, collateral circulation compensation is not yet fully set up, and makes to organize serious and lasting acute anoxia, and infarct can occur.Clinical study proves; occur after myocardial infarction; simple by self physiological revascularization; with adapt to ischemic change process very slow; the myocardial ischemia generally can only the compensatory coronary occlusion of part causing; when angioplasty, cononary artery bypass are invalid, increase artificially the concentration of regional myocardial somatomedin, to alleviating so that removing myocardial ischemia, alleviate myocardial necrosis and have potential possibility.The method of this manually operated angiogenesis was once once called " molecular bypass art ", was generally called at present Therapeutic Angiogenesis.
The red sage root is the dry root of the Labiatae salvia red sage root (Salvia miltiorrhiza Bge.), modern medicine thinks that the red sage root has coronary artery dilator, increases coronary flow, prevents the Cardiovascular such as myocardial ischemia and myocardial infarction, and the multiple anti-tumor activity such as Hepatoma therapy, cancer of the stomach, leukemia, cervical cancer.TANSHINONES (tanshi-none, DST) be ether or the ethanol extraction of red sage root root, the main fat-soluble effective constituent of the red sage root, be divided into 15 kinds of compositions such as tanshinone Ⅰ, tanshinone IIA, tanshinone ⅡB, Cryptotanshinone, dihydrotanshinone by its different chemical structure, be generically and collectively referred to as TANSHINONES.
But prior art does not instruct the tanshinone derivative can be for promoting the preparation in angiogenesis drug and antitumor drug.
Summary of the invention
The object of the present invention is to provide the preparation method of a kind of new tanshinone derivative and this tanshinone derivative, and the application in aspect preparation promotes angiogenesis drug and antitumor drug of this tanshinone derivative is provided.
In order to reach foregoing invention object, a kind of tanshinone derivative that first the present invention proposes is achieved through the following technical solutions:
A kind of tanshinone derivative, is characterized in that, the structural formula of described tanshinone derivative is as follows:
Secondly, the present invention also provides the preparation method of this tanshinone derivative, realizes by following technology:
100g total tanshinone efficient part, 500mmol phenyl aldehyde, 4mol ammonium acetate are dissolved in 1000ml ethanol, and at 20-90 DEG C stirring reaction 4-16h, take out afterwards reactant extraction and obtain total tanshinone reactant dry extract, finally described total tanshinone reactant dry extract is purified and obtained tanshinone derivative as claimed in claim 1.
In above-mentioned preparation method, the concrete steps of described purification are: get described total tanshinone reactant dry extract and carry out silica gel column chromatography, carry out gradient elution with the eluent that chloroform and methyl alcohol volume ratio are 30:1-1:1 afterwards, and to collect respectively chloroform and methyl alcohol volume ratio be that 30:1, chloroform and methyl alcohol volume ratio are that 20:1, chloroform and methyl alcohol volume ratio are that 10:1, chloroform and methyl alcohol volume ratio are the elutriant of 1:1 part; Get elutriant that chloroform and methyl alcohol volume ratio are 1:1 through Sephadex LH-20 column chromatography and high performance liquid chromatography separation and purification, obtain described tanshinone derivative; Wherein, the elutriant using in described high performance liquid chromatography is methanol aqueous solution, and the volume ratio of first alcohol and water is 35:100.
Finally, the invention provides the various application of described tanshinone derivative, specific as follows:
Described tanshinone derivative promotes the application in angiogenesis drug in preparation.Comprise:
Described tanshinone derivative promotes the application in animal blood vessels generating medicine in preparation.
Described tanshinone derivative promotes the application in vertebrates angiogenesis drug in preparation.
Described tanshinone derivative promotes the application in human vas generating medicine in preparation.
Described tanshinone derivative promotes the application in uriniferous tubules week capillary angiogenesis drug in preparation.
Described tanshinone derivative promotes the application in zebra fish angiogenesis drug in preparation.
Described tanshinone derivative is in the application of preparing in antitumor drug.Comprise,
Described tanshinone derivative is in the application of preparing in anti-lung-cancer medicament.
In above technical scheme, described promotion angiogenesis drug comprises the medicine of making following purposes: ischemic cardiovascular or angiogenesis inhibition disease due to the brain protection of atherosclerosis, coronary heart diseases and angina pectoris, cerebral infarction, vascular occlusion thromboangiitis, coronary stenosis, myocardial infarction, myocardial ischemia, occlusive vascular disease, ischemic rat brain damage, ischemic disease, Simultaneous reconstruction of postoperative defects of mandibular osteoradionecrosis, Aristolochic acid nephropathy, thrombosis.
Compared with prior art, the present invention has following beneficial effect:
(1) tanshinone derivative provided by the invention can be used for treating ischemic cerebrovascular, and has the feature of instant effect, drug safety.Tanshinone derivative has outstanding security individual structure, there is multiple pharmacological effect simultaneously, by improving the level of cerebrovascular endothelial NO and PGI2, reduce intracellular calcium concentration, suppressing L-glutamic acid discharges, reduce arachidonic acid content, suppress oxyradical and improve the mechanism such as activities of antioxidant enzymes, act on the multiple pathology links due to cerebral ischemia;
(2) tanshinone derivative provided by the invention can be used for preparing the medicine that improves blood confession redemption ischemic tissue by vasculogenesis, this curative effect of medication is definite, the medicine that can need to improve by vasculogenesis for the preparation for the treatment of the ischemic disease of blood confession is also the another new indication that butylphthalide continues outside cerebral ischemia indication simultaneously.
(3) tanshinone derivative provided by the invention can be used for preparing the medicine of the tumor diseases such as anti-lung cancer.
Brief description of the drawings
By the description of its exemplary embodiment being carried out below in conjunction with accompanying drawing, the above-mentioned feature and advantage of the present invention will become apparent and easily understand.
Fig. 1: the impact of the blood vessel disappearance of tanshinone derivative on VRI induction in zebra fish;
Fig. 2: tanshinone derivative on blood vessel endothelium injury animal intimal hyperplasia impact;
Fig. 3: tanshinone derivative is to all capillary vascular repairs of chronic nephropathy rat model uriniferous tubules and therapeutic action research.
Embodiment
Below in conjunction with accompanying drawing, the present invention is described in further detail, so that technician's of the same trade understanding:
The invention provides a kind of tanshinone derivative, called after TANSHINONES SF, its structure suc as formula under:
In the present embodiment, this tanshinone derivative preparation method is as follows:
Get total tanshinone efficient part 100.0g (35mmol), phenyl aldehyde 500mmol (60ml), ammonium acetate 4mol (about 300.0g) puts into the round-bottomed flask of 2000ml, add 1000ml ethanol to be heated after ultrasonic dissolution, stirring reaction 5 hours in 79 DEG C of oil baths, takes out the total tanshinone reactant dry extract that obtains 200g after reactant water and dichloromethane extraction 2 times.In this total tanshinone reactant dry extract, comprise this TANSHINONES SF.
In this reactions steps, the temperature of reaction of phenyl aldehyde, total tanshinone efficient part and ammonium acetate should be controlled between 20-90 DEG C, and the time of stirring reaction should be controlled between 4-16h.And above-mentioned concrete reaction conditions is a preferred embodiment.
By above-mentioned total tanshinone reactant dry extract routinely through silica gel column chromatography repeatedly, carry out gradient elution with the eluent that chloroform and methyl alcohol volume ratio are 30:1-1:1 afterwards, and to collect respectively chloroform and methyl alcohol volume ratio be that 30:1, chloroform and methyl alcohol volume ratio are that 20:1, chloroform and methyl alcohol volume ratio are that 10:1, chloroform and methyl alcohol volume ratio are the elutriant of 1:1 part; Get elutriant that chloroform and methyl alcohol volume ratio are 1:1 through Sephadex LH-20 column chromatography and high performance liquid chromatography separation and purification, wherein, the elutriant using in described high performance liquid chromatography is methanol aqueous solution, and the volume ratio of first alcohol and water is 35:100.Finally use thin layer plate (G254) to detect purity, obtain described TANSHINONES SF.
Structural Identification:
Lightpink powder, m.p.:152-153 DEG C, molecular formula is C
23h
20N
2o
2, HR-FAB-MS m/z:379.4866[M+Na] and+(Calcd.for C
55h
92o
21na, 379.4839), determine that compound molecular weight is 356.UV (MeOH) shows the obvious uv-absorbing of compound.Nuclear magnetic resonance data is in table 1, table 2.
Table 1 TANSHINONES SF
1h-NMR data (C
5d
5n, δ, ppm)
Table 2 TANSHINONES SF
13c-NMR data (C5D5N, δ, ppm)
| Position | C | Position | C |
| 1 | 29.83 | 15 | ? |
| 2 | 19.06 | 16 | ? |
| 3 | 37.63 | 17 | ? |
| 4 | 34.69 | 18 | 31.48 |
| 5 | 154.44 | 19 | 31.48 |
| 6 | 127.13 | 20 | ? |
| 7 | 127.44 | 21 | 136.5 |
| 8 | 131.58 | 22 | 126.75 |
| 9 | 137.1 | 23 | 128.98 |
| 10 | 135.1 | 24 | 129.03 |
| 11 | 128.76 | 25 | 128.98 |
| 12 | 168.1 | 26 | 126.75 |
| 13 | 182.0 | 27 | 145.28 |
| 14 | 180.44 | 28 | ? |
The impact of the blood vessel disappearance of embodiment 1 tanshinone derivative on VRI induction in zebra fish
Tanshinone derivative (Compound 10) is at VRI (VEGFR TYR kinase inhibitor II, hereinafter referred to as VRI) blood vessel of induction loses and carries out (500 μ g/ml) blood vessel on zebra fish model and recover test, result shows that this compound all shows recovery of blood vessels activity in various degree in the time of different concns, the highest recovery of blood vessels rate can reach 95%, and EC50 is about 0.026 μ M.As shown in Figure 1, when the basic, normal, high dosage of tanshinone derivative, can promote recovery of blood vessels, the highest recovery of blood vessels rate can reach 95%, and EC50 is about 0.026 μ M, and is dose-dependent effect.In Fig. 1, with relatively & p<0.01#p<0.001 of blank; With relatively * p<0.05 of model group, * * p<0.01, * * * p<0.001.
The angiogenesis promoting effect of embodiment 2 tanshinone derivatives to Human umbilical vein endothelial cells
Human umbilical vein endothelial cells (HUVE-12) adopts F-12K substratum, wherein contains Pidolidone, the 100U/ml mycillin of 2mM, 100 μ g/ml heparin, 30 μ g/ml endothelial cell growth element and 10%FBS.Get 2-5 for cell, inoculate 96 orifice plates by every hole 1 × 105/ml.Normal cultivation after 24 hours discards nutrient solution, changes the nutrient solution pre-treatment 24 hours of 0.5%FBS to reach cell synchronization.Test is divided into negative control group, positive controls (VEGF), tanshinone derivative group (6 dosage groups, final concentration is respectively 1,3,10,30,100,300 μ g/L), control group only adds 0.5%FBS and solvent, positive controls is the VEGF of 20 μ g/L containing concentration, establishes 6 multiple holes for every group.After cellar culture 48 hours, discard nutrient solution, microplate reader is measured the light absorption value at each hole 490nm and 690nm place according to XTT method.Test-results shows that tanshinone derivative has thick increment effect, and IC50 is 80 μ g/L.
The promoter action of embodiment 3 tanshinone derivatives to blood vessel endothelium injury animal intimal hyperplasia
40 Wistar rats, wherein after 30 anesthesia, the ligation of left femoral artery distal end, proximal part closes with artery clamp, inserts shaggy 0.035 inch of elasticity seal wire in the puncture of femoral artery far-end, repeatedly pumps 5 times, then twice rotation seal wire 120 spent, and each angle repeats to pump 5 times.Layer-by-layer suture subcutis and skin, local application of penicillin after operation is with preventing infection.Animal after modeling, with being divided into 3 groups, is respectively tanshinone derivative high and low dose group and positive controls, intravenous injection 3mg/kg respectively, the tanshinone derivative of 1mg/kg and the solvent of same volume, 1 times/day, totally 14 days.After off-test, take out inner film injury vessel segment, DAPI mark, Evans Blue are redyed, and observe intimal hyperplasia and reparation situation.After result shows that inner film injury blood vessel DAPI mark, 1% Evans Blue are redyed, the middle rete of fluorescence microscopy Microscopic observation red color visible fluorescence and the intimal hyperplasia cell of blue-fluorescence, find that positive controls intimal hyperplasia is not obvious, low dose group inner membrance has slight hyperplasia, and high dose group intimal hyperplasia is obvious.As shown in Figure 2, A figure is model control group, and visible intimal hyperplasia is not obvious, and B figure is tanshinone derivative high dose group, visible significantly intimal hyperplasia.
Embodiment 4 tanshinone derivatives are to all capillary vascular repairs of chronic nephropathy rat model uriniferous tubules and therapeutic action research
Wstar rat, 180-200g, gives Decoction of Caulis Aristolochiae Manshuriensis gavage (being equivalent to Stem of Manshurian Dutchmanspipe 30g/kg/ days), and 1 times/day, continuously gavage 16 weeks film forming afterwards, separately gets water that 8 animals give same volume as Normal group.24 of animals after film forming, are divided into 3 groups at random, are respectively tanshinone derivative high and low dose group and positive controls, intravenous injection 3mg/kg respectively, the tanshinone derivative of 1mg/kg and the solvent of same volume, 1 times/day, totally 14 days.After off-test, put to death respectively each group of rat.Get nephridial tissue sample, 4% paraformaldehyde solution is fixed, and 4 degree are preserved.Result shows to damage capillary vessel DAPI mark, 1% Evans Blue redye after, the middle rete of fluorescence microscopy Microscopic observation red color visible fluorescence and the intimal hyperplasia cell of blue-fluorescence, find that positive controls intimal hyperplasia is not obvious, low dose group inner membrance has slight hyperplasia, and high dose group intimal hyperplasia is obvious.As shown in Figure 3, A schemes positive control group, and visible intimal hyperplasia is not obvious, and B figure is tanshinone derivative high dose group, visible significantly intimal hyperplasia, and C figure is low dose group, there is slight hyperplasia in visible internal film tissue.
The external evoked Wide colon-cancer cell of embodiment 5 tanshinone derivative apoptosis
Wide colon-cancer cell inoculation after recovery is gone down to posterity.The cell in vegetative period of taking the logarithm.Be inoculated in 24 porocyte culture plates with 1 × 106/ml density, after 12h, be divided into 4 groups and add medicine.Be respectively Normal group, the high, medium and low intervention group of tanshinone derivative (adding respectively tanshinone derivative concentration is 5,25,125 μ g/L), separately establish the perfect medium group that does not add cell, establish 4 multiple holes for every group, put 37 degree, in CO2 incubator, cultivate after 12,24,36 hours, mtt assay detects the inhibiting rate experimental result of tumour cell is seen the following form, and calculation formula is as follows: cell mortality=[1-(experimental group OD mean value/blank group OD value)] × 100%.
Result shows, tanshinone derivative effect is after 12,24 hours, and with control group comparison, the increment inhibiting rate of colon-cancer cell significantly increases, and statistical procedures has significant difference; And along with the each medication group of increase of dosage has increase trend to the proliferation inhibition rate of colon-cancer cell, there were significant differences for statistical procedures.Flow cytometer carries out morphological analysis result and shows, occurs obvious apoptotic cell after tanshinone derivative medication.Prompting tanshinone derivative cytotoxicity may realize by cell death inducing, as shown in table 3.
The restraining effect (mean ± SD) of table 3 tanshinone derivative to colon-cancer cell
The restraining effect of embodiment 6 tanshinone derivatives on Lewis lung cancer and the impact of cell cycle
C57BL/6 mouse, male and female half and half, 18-20 gram.Right fore oxter subcutaneous vaccination Lewis lung cancer noumenal tumour.Latter the 1st day of inoculation, animal is divided into 5 groups at random, 10 every group.The high, medium and low dosage group of cis-platinum, tanshinone derivative that is respectively physiological saline only of model group abdominal injection 0.4ml/, positive controls abdominal injection 1mg/kg is the tanshinone derivative of abdominal injection 3,10,30mg/kg respectively.Injection 5 days, cuts open and gets each treated animal tumour, thymus gland, spleen on the 11st continuously, takes quality.Calculate tumour inhibiting rate and organ index.And cut open and get fresh tumor tissues, prepare cell suspension, to get suspension 100ul and add RNA enzyme, 37 degree water-baths 30 minutes, add PI 500ul, 4 degree lucifuge dyeing 10 minutes.Flow cytometer obtains cell, analysis of cells cycle and apoptosis rate.
Result shows: each administration group is compared with control group, and average knurl quality significantly reduces, and difference has statistical significance, and is obvious dose-dependence, and best with heavy dose of administration group tumor killing effect, tumour inhibiting rate is 68%.Tanshinone derivative group is compared with positive controls, and thymus index significantly increases, and difference has statistical significance.Tanshinone derivative group and control group comparison, G0/G1 phase cell content increases, and S phase cell content reduces, and difference has statistical significance, and apoptosis rate significantly increases, and is obvious dose-dependence, as shown in table 4.
The restraining effect of table 4 tanshinone derivative on Lewis lung cancer and the impact on dirty cell cycle and apoptosis rate
As from the foregoing, the present invention has following beneficial effect:
(1) tanshinone derivative of the present invention can be used for treating ischemic cerebrovascular, and has the feature of instant effect, drug safety.Tanshinone derivative has outstanding security individual structure, there is multiple pharmacological effect simultaneously, by improving the level of cerebrovascular endothelial NO and PGI2, reduce intracellular calcium concentration, suppressing L-glutamic acid discharges, reduce arachidonic acid content, suppress oxyradical and improve the mechanism such as activities of antioxidant enzymes, act on the multiple pathology links due to cerebral ischemia.
(2) tanshinone derivative of the present invention can be used for preparing the medicine that improves blood confession redemption ischemic tissue by vasculogenesis, this curative effect of medication is definite, the medicine that can need to improve by vasculogenesis for the preparation for the treatment of the ischemic disease of blood confession is also the another new indication that butylphthalide continues outside cerebral ischemia indication simultaneously.
(3) tanshinone derivative of the present invention can be used for preparing the medicine of the tumor diseases such as anti-lung cancer.
Although the present invention with preferred embodiment openly as above; but it is not for limiting claim; any those skilled in the art without departing from the spirit and scope of the present invention; can make possible variation and amendment, therefore protection scope of the present invention should be as the criterion with the scope that the claims in the present invention were defined.
Claims (11)
1. a tanshinone derivative, is characterized in that, the structural formula of described tanshinone derivative is as follows:
2. a preparation method for tanshinone derivative as claimed in claim 1, is characterized in that preparing as follows:
100g total tanshinone efficient part, 500mmol phenyl aldehyde, 4mol ammonium acetate are dissolved in 1000ml ethanol, and at 20-90 DEG C stirring reaction 4-16h, take out afterwards reactant extraction and obtain total tanshinone reactant dry extract, finally described total tanshinone reactant dry extract is purified and obtained tanshinone derivative as claimed in claim 1;
Described purification is carried out silica gel column chromatography for getting described total tanshinone reactant dry extract, carry out gradient elution with the eluent that chloroform and methyl alcohol volume ratio are 30:1-1:1 afterwards, and to collect respectively chloroform and methyl alcohol volume ratio be that 30:1, chloroform and methyl alcohol volume ratio are that 20:1, chloroform and methyl alcohol volume ratio are that 10:1, chloroform and methyl alcohol volume ratio are the elutriant of 1:1 part; Get elutriant that chloroform and methyl alcohol volume ratio are 1:1 through Sephadex LH-20 column chromatography and high performance liquid chromatography separation and purification, obtain described tanshinone derivative; Wherein, the elutriant using in described high performance liquid chromatography is methanol aqueous solution, and the volume ratio of first alcohol and water is 35:100.
3. the application of a kind of tanshinone derivative as claimed in claim 1, is characterized in that: described tanshinone derivative promotes the application in angiogenesis drug in preparation.
4. the application of a kind of tanshinone derivative as claimed in claim 3, is characterized in that: described tanshinone derivative promotes the application in animal blood vessels generating medicine in preparation.
5. the application of a kind of tanshinone derivative as claimed in claim 4, is characterized in that: described tanshinone derivative promotes the application in vertebrates angiogenesis drug in preparation.
6. the application of a kind of tanshinone derivative as claimed in claim 5, is characterized in that: described tanshinone derivative promotes the application in human vas generating medicine in preparation.
7. the application of a kind of tanshinone derivative as claimed in claim 5, is characterized in that: described tanshinone derivative promotes the application in uriniferous tubules week capillary angiogenesis drug in preparation.
8. the application of a kind of tanshinone derivative as claimed in claim 5, is characterized in that: described tanshinone derivative promotes the application in zebra fish angiogenesis drug in preparation.
9. the application of a kind of tanshinone derivative as described in claim 3-8 any one; it is characterized in that, described promotion angiogenesis drug comprises the medicine of following purposes: ischemic cardiovascular or angiogenesis inhibition disease due to the brain protection of atherosclerosis, coronary heart diseases and angina pectoris, cerebral infarction, vascular occlusion thromboangiitis, coronary stenosis, myocardial infarction, myocardial ischemia, occlusive vascular disease, ischemic rat brain damage, ischemic disease, Simultaneous reconstruction of postoperative defects of mandibular osteoradionecrosis, Aristolochic acid nephropathy, thrombosis.
10. the application of a kind of tanshinone derivative as claimed in claim 1, is characterized in that: described tanshinone derivative is in the application of preparing in antitumor drug.
The application of 11. a kind of tanshinone derivatives as claimed in claim 10, is characterized in that: described tanshinone derivative is in the application of preparing in anti-lung-cancer medicament.
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| CN101863894A (en) * | 2010-06-01 | 2010-10-20 | 广东药学院 | Tanshinone II A derivative and preparation method and application thereof |
| CN102603861A (en) * | 2012-02-25 | 2012-07-25 | 中国科学院昆明植物研究所 | Tanshinone derivatives, medicine compositions thereof, and purposes thereof in medicine |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101863894A (en) * | 2010-06-01 | 2010-10-20 | 广东药学院 | Tanshinone II A derivative and preparation method and application thereof |
| CN102603861A (en) * | 2012-02-25 | 2012-07-25 | 中国科学院昆明植物研究所 | Tanshinone derivatives, medicine compositions thereof, and purposes thereof in medicine |
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| Development》.2010,第14卷(第5期),1102-1109. * |
| Diterpenoids from Salvia miltiorrhiza;Hang-Ching Lin 等;《Phytochemistry》;20000430;第53卷;951-953 * |
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