CN101732294A - Anti-tumor application of tanshinone compound - Google Patents
Anti-tumor application of tanshinone compound Download PDFInfo
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- CN101732294A CN101732294A CN200910155042A CN200910155042A CN101732294A CN 101732294 A CN101732294 A CN 101732294A CN 200910155042 A CN200910155042 A CN 200910155042A CN 200910155042 A CN200910155042 A CN 200910155042A CN 101732294 A CN101732294 A CN 101732294A
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Abstract
The invention relates to an application of a tanshinone compound in preparing anti-tumor medicaments, and the prepared medicaments can resist tumors, such as brain tumors, lung cancer, liver caner, breast cancer, prostatic cancer, pancreatic cancer, cervical cancer, gastric cancer, esophagus cancer, and the like. Proved by experiments, the tanshinone compound is concentration-dependent to suppress the proliferation of tumor cells. The compound can obviously induce the expression of quinone reductase and obviously suppress the generation of tumor vessels, thus the compound can also be used for preparing cancer chemical prevention medicaments, anti-inflammatory medicaments and medicaments for suppressing the generation of the tumor vessels. Frequently used low-price reagents, such as alcohol, chloroform, methanol, silica gel, and the like, are used for separating tanshinone compound monomers from medicinal materials. The method is simple and reliable, has low cost and high efficiency, can be used for carrying out industrialized mass production and is beneficial to popularization and application. The tanshinone compound has a structural general formula disclosed in the specification.
Description
Technical field
The invention belongs to plants ' medicinal component and antitumoral compounds field, particularly be the effective ingredient tanshinone compound and the application thereof with obvious prevention and treatment function of tumor of from salviamiltiorrhizabung (Salvia miltiorrhiza Bge.), extracting.
Background technology
The whole world has the millions of people to die from cancer every year at present, and new cases are also increasing year by year.Have the million people to die from cancer every year in China's 1,300,000,000 populations, and cancer has become first cause of the death.
At present, chemotherapy and radiotherapy are the first-selection of treatment cancer, but to the specificity of tumor cell relatively poor thereby have bigger toxic and side effects and some tumor cell to chemotherapy and radiation handle insensitive, therefore limited their application in clinical to a great extent.In recent years, cancerous cell can be killed and wounded specifically and to the less medicine of normal cell toxicant negative interaction in order to develop.Therefore, the new antitumor drug of research preparation becomes the focus of biomedicine field.
Radix Salviae Miltiorrhizae (Salvia miltiorrhiza Bge.) is a Labiatae Radix Salviae Miltiorrhizae platymiscium, is a conventional Chinese medicine.Modern pharmacology studies show that Radix Salviae Miltiorrhizae extract has antitumor action, has wherein mainly studied the anti-nonsmall-cell lung cancer of tanshinone, the effect of breast carcinoma, seldom reports the antitumor action of other tanshinone compound.
Summary of the invention
The purpose of this invention is to provide the application of a kind of tanshinone compound in the preparation antitumor drug, described tanshinone compound has following general structure:
Wherein, R
1Can be H, CH
3, CH
2CH
3, CH
2CH=C (CH
3)
2, OH, OCH
3, NH
2,=O, Δ
1,2Etc. substituent any; R
2Can be=CH
2, CH
3, (CH
3)
2Deng in the substituted radical any.Relate generally to following 4 kinds of chemical compounds:
1 (miltirone) 2 (1-oxomiltirone)
3(4-methylenemiltirone) 4(1，2-didehydromiltirone)
The described antitumor of chemical compound of the present invention comprises: cerebroma, pulmonary carcinoma, hepatocarcinoma, breast carcinoma, carcinoma of prostate, cancer of pancreas, cervical cancer, gastric cancer, esophageal carcinoma etc.
The medicine that chemical compound of the present invention also can be used to prepare cancer chemoprophylactic drug, anti-inflammatory drug and suppress tumor-blood-vessel growth.
Carry out the screening of antitumor action with mtt assay, the result shows, the tumor cell line that tanshinone compound of the present invention is handled such as people's marrow leukaemia (HL60), brain glioblastoma cell (U87), breast cancer cell (MCF-7), lung carcinoma cell (H460), human liver cancer cell (HepG2), human prostate cell (PC3), human colon cancer cell (SW480), human cervical carcinoma cell (Hela) are compared cell-proliferation activity with corresponding not dosing matched group and have been descended respectively along with increasing with concentration, illustrates that chemical compound is concentration dependent inhibition tumor cell proliferation.
Carry out the chemoprophylactic screening of cancer with mtt assay, the result shows that tanshinone compound of the present invention can significantly be induced the expression of quinone reductase.
Carry out the research of tumor-blood-vessel growth inhibitory action with the official jargon forming method, the result shows that tanshinone compound of the present invention can significantly suppress the effect of tumor-blood-vessel growth.
Chemical compound of the present invention can combine with carrier commercially available or commonly used, is used for prevention or treatment tumor and cancer.Described medicine can be tablet or injection.
The present invention the experiment proved that described tanshinone compound is the effective antitumour agent.The present invention separates from Chinese crude drug with cheap, common reagent such as ethanol, chloroform, methanol and silica gel and obtains miltirone compounds monomer, and this method is simple and reliable, and cost is low, and the efficient height can carry out industrialized great production, helps applying.
Description of drawings
Fig. 1 is the tumor vessel inhibition test result of tanshinone compound 1.
Fig. 2 is the tumor vessel inhibition test result of tanshinone compound 2.
Fig. 3 is the tumor vessel inhibition test result of tanshinone compound 3.
Fig. 4 is the tumor vessel inhibition test result of tanshinone compound 4.
The specific embodiment
Below embodiment by specific embodiment is described in further detail content of the present invention.But embodiment should be interpreted as limitation of the present invention.Do not breaking away under the above-mentioned state of mind of the present invention, various replacement means or change according to ordinary skill knowledge and conventional means are made all are included within the present invention.
The preparation of embodiment 1 chemical compound 1-4
Red rooted salvia (3kg) is with 95% ethanol extraction of 8 times of amounts 3 times, and ethanol extraction extracts successively with petroleum ether, dichloromethane, n-butyl alcohol.(70g) is dissolved in the 100mL ethyl acetate with dichloromethane layer, adds 70g200-300 order chromatographic silica gel and mixes sample.With 300g 200-300 order chromatographic silica gel wet method dress post, sample is added, fixedly pillar.Wash pillar with petroleum ether, change petroleum ether behind the full of liquid in pillar: ethyl acetate (100: 1) mobile phase is carried out eluting.Respectively with petroleum ether: ethyl acetate 100: 1,50: 1,20: 1,16: 1,10: 1,8: 1,6: 1,4: 1,3: 1,2: 1,1.5: 1,1: 1,1: 1.5,1: 2,1: 3,1: 5,1: 10, carry out eluting at 1: 50, each gradient elution volume is 1.6L, is divided into 4 bottles, every bottle of 400mL.With the gained solution concentration, concentrated solution is transferred to the 10mL penicillin bottle, behind the some plate analysis same sample is merged.To petroleum ether: the part of 8: 1 eluting of ethyl acetate is separated, and main separation method is anti-phase preparation liquid phase.To carry out eluting from 50%-93% in the gradient acetonitrile/water 60min, 26.3min gets 2, and 46.5min gets 1, and 40min gets 4,3 (again with 77% acetonitrile isocratic elution purification).Its NMR data are respectively referring to table 1 and table 2.
Table 1 chemical compound 1 and 2 proton nmr spectra and carbon spectrum data (CDCl
3,
1H, 500MHz,
13C, 125MHz)
Table 2 chemical compound 3 and 4 proton nmr spectra and carbon spectrum data (CDCl
3,
1H, 500MHz,
13C, 125MHz)
The extracorporeal anti-tumor function experiment of embodiment 2 chemical compound 1-4
The take the logarithm every hole 3 * 10 of cell of phase
4Be inoculated on 96 orifice plates, behind the 12h, abandon supernatant, press following grouping administration: normal control group and dosing group (concentration 0-100 μ M), establish 6 multiple holes for every group, cultivate 24h, abandon supernatant, the culture fluid 50 μ l that add band MTT cultivate 4h (0.5mg/mL), add 100 μ l DMSO, vibration 1h, the 570nm place surveys the OD value on microplate reader.
The result shows that after the dosing, activity of tumor cells obviously descends, and activity of tumor cells reduces along with the increase of drug level.The result sees table 3 for details.PC3 (prostate gland cancer cell), U87 (brain glioblastoma cell), Hela (cervical cancer cell), SGC-7901 (stomach cancer cell), above-mentioned cell strain are all available from Chinese Academy of Sciences's Shanghai cell biological institute.
Table 3 is the antitumor activity in vitro result of tanshinone compound 1-4.
The quinone reductase of embodiment 3 chemical compound 1-4 is induced experiment
The take the logarithm Hepa 1c1c7 cell of phase, every hole 2 * 10
4Be inoculated on 96 orifice plates, behind the 24h, abandon supernatant, click the grouping administration: normal control group and dosing group (concentration 0-100 μ M), establish 6 multiple holes, cultivate 24h for every group, abandon supernatant, add digitonin and make lysis, the culture fluid 200 μ l that the back adds band MTT cultivate 5min (0.5mg/mL), and the 550nm place surveys the OD value on microplate reader.
The result is referring to table 4, and table 4 shows that after the dosing, medicine can obviously be induced the expression of quinone reductase, and described cell is all available from ATCC.
The quinone reductase of table 4 miltirone compounds 1-4 is induced the result.
The tumor-blood-vessel growth of embodiment 4 TANSHINONES chemical compound 1-4 suppresses experiment
Manufacture the dosing plate and get the dissolved TANSHINONES storing solution of DMSO (0,1,2 * 200 μ M) 10 μ L respectively in 96 orifice plates, every hole adds 190 μ L PBS dilution, mixing again.Standby.
1. shop glue is got 45 μ L GFR-Matrigel (45 μ L/well) in 96 orifice plates of pre-cooling, and vibration is paved it, does not introduce bubble.Place 10min in 37 ℃ of incubators.Take out stand-by.
2. preparation cell suspension is got the EAhy926 cell, and digestion stops digestion with low blood serum medium (1 ‰ pairs are anti-for DMEM, 2%FBS), counting, and centrifugal, resuspended with low blood serum medium, being made into cell density is 3 * 10
5The cell suspension of cell/mL.
3. be seeded in the low serum cell suspension of adding 90 μ L in 96 orifice plates of having completed glue, add each concentration TANSHINONES medicinal liquid that 10 μ L diluted again.
4. cultivate with plate put into hypoxia culture box (37 ℃, 95%N
2, 5%CO
2) middle continuous culture 6h.
5. take pictures and get 5 visuals field at random under the Leica optical microscope and take pictures.
The result shows that after the dosing, medicine can obviously suppress the formation of official jargon, and described cell is all available from ATCC (referring to Fig. 1-4).The result shows, after chemical compound 1-4 acts on cell, along with the increase of compound concentration, can significantly suppress the formation of tube chamber, illustrates to have potential tumor-blood-vessel growth inhibitory action.
Claims (5)
1. the application of tanshinone compound in the preparation antitumor drug, described tanshinone compound has following general structure:
Wherein: R
1Be H, CH
3, CH
2CH
3, CH
2CH=C (CH
3)
2, OH, OCH
3, NH
2,=O or Δ
1,2In any; R
2For=CH
2, CH
3Or (CH
3)
2In any;
Be specifically related to following 4 kinds of chemical compounds:
1 (miltirone) 2 (1-oxomiltirone)
3(4-methylenemiltirone) 4(1，2-didehydromiltirone)
2. a kind of tanshinone compound according to claim 1 prepares the application in the antitumor drug, it is characterized in that, described tumor comprises: cerebroma, carcinoma of prostate, cervical cancer or gastric cancer.
3. a kind of tanshinone compound according to claim 1 prepares the application in the antitumor drug, it is characterized in that the application of described chemical compound in the preparation anti-inflammatory drug.
4. a kind of tanshinone compound according to claim 1 prepares the application in the antitumor drug, it is characterized in that the application of described chemical compound in preparation inhibition tumor-blood-vessel growth medicine.
5. a kind of tanshinone compound according to claim 1 prepares the application in the antitumor drug, it is characterized in that the application of described chemical compound in preparation quinone reductase derivant.
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|---|---|---|---|
| CN200910155042A CN101732294A (en) | 2009-12-14 | 2009-12-14 | Anti-tumor application of tanshinone compound |
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|---|---|---|---|
| CN200910155042A CN101732294A (en) | 2009-12-14 | 2009-12-14 | Anti-tumor application of tanshinone compound |
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| CN101732294A true CN101732294A (en) | 2010-06-16 |
Family
ID=42456666
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102579461A (en) * | 2012-01-12 | 2012-07-18 | 中国药科大学 | Application of tanshinone IIA in preparation of medicament for treating p53 mutational or deficient tumor |
| CN103845314A (en) * | 2014-02-13 | 2014-06-11 | 浙江省中医院 | Application of miltirone in preparation of antitumor drugs |
| CN104173368A (en) * | 2014-09-17 | 2014-12-03 | 陈岳芹 | Composition for treating cervical cancer |
| CN108047020A (en) * | 2018-01-04 | 2018-05-18 | 中国科学院昆明植物研究所 | Miltionone derivative and its pharmaceutical composition and its application in pharmacy |
| CN109485691A (en) * | 2017-09-12 | 2019-03-19 | 上海交通大学医学院附属新华医院 | Tanshinone compound and its for treating angiomatous purposes |
| CN110420202A (en) * | 2019-08-08 | 2019-11-08 | 浙江中医药大学附属第一医院 | A kind of rosin alkanes tricyclic diterpene reactive compound application in preparation of anti-tumor drugs |
| CN114984237A (en) * | 2022-04-29 | 2022-09-02 | 天津中医药大学 | Tanshinone IIA modifier and preparation method and application thereof |
-
2009
- 2009-12-14 CN CN200910155042A patent/CN101732294A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102579461A (en) * | 2012-01-12 | 2012-07-18 | 中国药科大学 | Application of tanshinone IIA in preparation of medicament for treating p53 mutational or deficient tumor |
| CN103845314A (en) * | 2014-02-13 | 2014-06-11 | 浙江省中医院 | Application of miltirone in preparation of antitumor drugs |
| CN103845314B (en) * | 2014-02-13 | 2016-01-20 | 浙江省中医院 | A kind of miltirone is preparing the application in antitumor drug |
| CN104173368A (en) * | 2014-09-17 | 2014-12-03 | 陈岳芹 | Composition for treating cervical cancer |
| CN109485691A (en) * | 2017-09-12 | 2019-03-19 | 上海交通大学医学院附属新华医院 | Tanshinone compound and its for treating angiomatous purposes |
| WO2019052477A1 (en) * | 2017-09-12 | 2019-03-21 | 上海交通大学医学院附属新华医院 | Tanshinone compound and use thereof for treating hemangioma |
| CN108047020A (en) * | 2018-01-04 | 2018-05-18 | 中国科学院昆明植物研究所 | Miltionone derivative and its pharmaceutical composition and its application in pharmacy |
| CN110420202A (en) * | 2019-08-08 | 2019-11-08 | 浙江中医药大学附属第一医院 | A kind of rosin alkanes tricyclic diterpene reactive compound application in preparation of anti-tumor drugs |
| CN110420202B (en) * | 2019-08-08 | 2022-12-20 | 浙江中医药大学附属第一医院 | Application of abietane tricyclic diterpene active compounds in preparation of antitumor drugs |
| CN114984237A (en) * | 2022-04-29 | 2022-09-02 | 天津中医药大学 | Tanshinone IIA modifier and preparation method and application thereof |
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Open date: 20100616 |