CN103127102A - Application of 8-propyl dicyan berberine in preparation of antitumor drug - Google Patents
Application of 8-propyl dicyan berberine in preparation of antitumor drug Download PDFInfo
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- CN103127102A CN103127102A CN2011103752251A CN201110375225A CN103127102A CN 103127102 A CN103127102 A CN 103127102A CN 2011103752251 A CN2011103752251 A CN 2011103752251A CN 201110375225 A CN201110375225 A CN 201110375225A CN 103127102 A CN103127102 A CN 103127102A
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Abstract
The invention belongs to the chemical industry field and the medicine field, and relates to an application of 8-propyl dicyan berberine in preparation of antitumor drugs. The invention provides the application of 8-propyl dicyan berberine in preparation of antitumor drugs, and the tumor cells comprise liver cancer cells, leukemia cells, lung adenocarcinoma cells, and pancreas cancer cells. The 8-propyl dicyan berberine belongs to a natural product, has little toxic and side effect, high bioavailability, and stable properties, and has clinical application value. The micromolecular compound of the invention can be developed as a new antitumor drug or its auxiliary component, has obvious tumor suppression effect, is green and environment-friendly, and provides a new approach and means for treating and curing tumors.
Description
Technical field
The invention belongs to chemical field and field of medicaments, relate to the application of 8-the third dicyan berberine in the preparation antitumor drug.
Background technology
8-the third dicyan berberine is the alkali derivant that 8,8-two replaces-13,13a-dihydro Radix Berberidis Amurensis, and its structural formula is as follows:
This compound appear in the newspapers at head in 1978 (The methylene signature of reduced isoquinolines:a PMR structural correlation..Heterocycles (1978), 9 (2), 145-52.).Next year, Moniot etc. further described its chemical constitution (Chemistry of 8-chloroberberine.Journal of Pharmaceutical Sciences (1979), 68 (6), 705-8.)
The Chinese invention patent application that application number is 200910049688.1, name is called " 8; 8-two replaces-13; 13a-dihydro berberine derivant and pharmaceutical composition thereof and purposes " discloses the synthesis preparation method of 8-the third dicyan berberine, and show that by experiment above-claimed cpd has the effect that promotes glucose absorption to muscle cell, whole animal test shows that such compound has the carbohydrate tolerance of improvement and insulin resistant, alleviates obesity, alleviates the effect such as fatty liver, and bioavailability is high, strengthened the drug effect in body, simultaneously Stability Analysis of Structures under acid condition.This compounds can be used for treating type 2 diabetes mellitus, obesity, fatty liver or its complication.
8-the third dicyan berberine is natural product, and side effect is little, bioavailability is high, stable in properties, has clinical use value.But, up to now, not yet see the report about the relevant anti-tumor aspect of this compound.
Summary of the invention
The new medicinal usage that the purpose of this invention is to provide 8-the third dicyan berberine.
The invention provides the application of 8-the third dicyan berberine in the preparation antitumor drug.Described tumor can be hepatocarcinoma, leukemia, adenocarcinoma of lung or cancer of pancreas.Described antitumor drug is injection or tablet.Described antitumor drug can be anti-leukemia medicine.
The invention provides a kind of method that suppresses tumor cell in vitro propagation, 8-the third dicyan berberine is added in the culture fluid of tumor cell.Described tumor cell is hepatoma carcinoma cell, leukaemia, lung adenocarcinoma cell or pancreatic cancer cell.Generally speaking, adding the final concentration of 8-the third dicyan berberine is 1-100 μ M.For example, 1-5 μ M, 1-10 μ M, 1-20 μ M, 1-50 μ M, 10-50 μ M, 10-60 μ M, etc.
The present invention also provides a kind of antitumor drug, and the active component of described antitumor drug is 8-the third dicyan berberine.Described tumor can be hepatocarcinoma, leukemia, adenocarcinoma of lung or cancer of pancreas.
Micromolecular compound of the present invention can adopt the preparation method preparation of various routines.For example, adopt the synthetic method of artificial chemistry.
Utilize micromolecular compound of the present invention, by various conventional screening techniques, can filter out with 8-the third dicyan berberine interactional material occurs, as receptor, inhibitor or pick up anti-dose etc.
The present invention and inhibitor thereof, pick up anti-dose etc., when using (administration) in treatment, can provide different effects.Usually, these materials can be formulated in nontoxic, inertia with pharmaceutically acceptable aqueous carrier medium in, wherein pH is about 5-8 usually, preferably pH is about 6-8, pH value can change to some extent with the character that is formulated material and disease to be treated.The pharmaceutical composition for preparing can carry out administration by conventional route, comprising (but being not limited to): intramuscular, intraperitoneal, subcutaneous, Intradermal or topical.
Take 8-the third dicyan berberine of the present invention as example, can be with itself and suitable pharmaceutically acceptable carrier coupling.This class pharmaceutical composition contains compound and pharmaceutically acceptable carrier or the excipient for the treatment of effective dose.This class carrier comprises (but being not limited to): saline, buffer, glucose, water, glycerol, ethanol and combination thereof.Pharmaceutical preparation should be complementary with administering mode.8-the third dicyan berberine of the present invention can be made into the injection form, for example is prepared by conventional method with normal saline or the aqueous solution that contains glucose and other adjuvant.Pharmaceutical composition such as Tablet and Capsula can be prepared by conventional method.Pharmaceutical composition such as injection, solution, Tablet and Capsula should be made under aseptic condition.The dosage of active component is the treatment effective dose, for example every day about 5 mg/kg body weight of 1 microgram/kg body weight-Yue.In addition, 8-the third dicyan berberine of the present invention also can use together with the other treatment agent.
When 8-the third dicyan berberine of the present invention is used as medicine, the 8-third dicyan berberine for the treatment of effective dose can be applied to mammal, wherein should treat effective dose usually at least about 10 micrograms/kg body weight, and in most of the cases be no more than approximately 8 mg/kg body weight, preferably this dosage is the about 1 mg/kg body weight of 10 micrograms/kg body weight-Yue.Certainly, concrete dosage also should be considered the factors such as route of administration, patient health situation, and these are all within the skilled practitioners skill.
The invention provides the application of 8-the third dicyan berberine in the preparation antitumor drug.8-the third dicyan berberine is natural product, obviously the propagation of inhibition tumor cell.Micromolecular compound of the present invention is developed as new antitumor drug or its auxiliary element, and tumor killing effect is obvious, environmental protection, and will and cure tumor for treatment provides a kind of new approach and means.
The specific embodiment
Experimental technique:
1. cell recovery
1) take out cryopreservation tube from liquid nitrogen container, directly drop in 37 ℃ of warm water, and frequently shake and make it melt as early as possible.
2) take out cryopreservation tube from 37 ℃ of water-baths, with suction pipe sucking-off cell suspension, inject centrifuge tube and add culture fluid more than 10 times, low-speed centrifugal after mixing is abandoned supernatant, then is repeated to wash once with culture fluid.
3) with after the suitable dilution of culture fluid, the inoculated and cultured bottle is placed on 37 ℃ of standing cultivations of incubator, changes culture fluid next day, continues to cultivate.Go down to posterity when being cultured to finite concentration.The PANC-1 cell culture is in containing the DMEM high glucose medium of 10%Gibico hyclone, and SMMC-7721 and QGY cell culture contain 100U/ml penicillin and 100 μ g/ml streptomycins in culture medium in containing the DMEM high glucose medium of 10% hyclone.
2. passage is cultivated
The situation of observation of cell growth every day is grown to approximately 90% and is gone down to posterity when converging (attached cell) in culture bottle when cell, approximately went down to posterity once every 2-4 days.One bottle goes down to posterity into three bottles, or a 25cm
2Go down to posterity in a 75cm
2Culture bottle in.Method:
1) with 1 * phosphate buffer washed cell once.
2) add 2-3ml trypsinization liquid digestion, be placed in 37 ℃ of incubator numbers minute.Pat Tissue Culture Flask with hands, make cell separation.
3) suitable culture medium with the Gibico hyclone that contains 10-15% stops trypsinization.Cell is sub-packed in new culture bottle, continues to cultivate.
3. cell cryopreservation
1) get the cell tryptase protease digestion that is cultured to exponential phase, be collected in centrifuge tube and counting, centrifugal.
2) reject trypsin and old culture fluid add the frozen culture fluid (containing 10%DMSO, 40%DMEM and 50%Gibico hyclone) that configures, and in cryopreserving liquid, the ultimate density of cell is 0.5-1 * 10
7/ ml.Blow and beat gently with suction pipe and make cell even, then be distributed in aseptic cryopreservation tube, every pipe adds 1-1.5ml.
3) cryopreservation tube is put into freezing storing box and put-80 ℃ of quick-freezings, move in liquid nitrogen container after 5 hours and preserve.
4. experimental procedure and result
K562 cell (available from Chinese Academy of Sciences's cell bank) 1 * 10
4/ hole is seeded to 96 orifice plates, cultivates to make it in 24 hours to add 8-the third dicyan berberine (available from Shanghai Pharmaceutical Inst., Chinese Academy of Sciences) after adherent, establishes 6 Concentraton gradient, and each concentration is established 3 multiple holes.Cell is at 37 ℃, 5%CO
2Cultivate after 72 hours under condition, outwell culture fluid, measure cell survival rate with MTS test kit (Promega company).
Method of testing is: cell is washed one time with serum-free medium, added the MTS chromophoric solution (adding 2ml solution 1 and 100 μ l solution 2 in the 10ml serum-free medium, fully mixing) for preparing in advance according to the amount of 100 μ l/well.Do not have the hole of cell to be made as this bottom outlet with one, absorb in order to the bias light of calibration solution.Cell is put into cell culture incubator to be continued to cultivate 2～4 hours, then read absorbance value (reference wavelength 630-700nm with microplate reader, measure wavelength 490nm), calculate cell survival rate, to measure hole absorbance value/control wells absorbance value as the numerical value of cell survival rate.According to cell survival rate, calculate 8-the third dicyan berberine to the IC50 value of HGC cell.
IC50 refers to a suppressed half
InhibitorConcentration.Here be the K562 cell quantity and be the concentration of half 8-third a dicyan berberine of contrast.The calculating of IC50 generally need to be measured the dosage effect more than 5, then obtains function calculation by curve fitting and get.
Result: 8-the third dicyan berberine is 46.21 μ M to the IC50 value of K562 cell.
Claims (9)
1.8-the application of the third dicyan berberine in the preparation antitumor drug.
2. application as claimed in claim 1, is characterized in that, described tumor is leukemia.
3. application as claimed in claim 1, is characterized in that, described antitumor drug is anti-leukemia medicine.
4. application as claimed in claim 1, is characterized in that, the dosage form of described antitumor drug is injection, tablet or capsule.
5. a method that suppresses tumor cell in vitro propagation, is characterized in that, 8-the third dicyan berberine is added in the culture fluid of tumor cell.
6. method as claimed in claim 5, is characterized in that, described tumor cell is the leukaemia.
7. method as claimed in claim 5, is characterized in that, the final concentration that adds 8-the third dicyan berberine is 1-50 μ M.
8. an antitumor drug, is characterized in that, the active component of described antitumor drug is 8-the third dicyan berberine.
9. antitumor drug as claimed in claim 8, is characterized in that, described tumor is leukemia.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2011103752251A CN103127102A (en) | 2011-11-22 | 2011-11-22 | Application of 8-propyl dicyan berberine in preparation of antitumor drug |
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| CN2011103752251A CN103127102A (en) | 2011-11-22 | 2011-11-22 | Application of 8-propyl dicyan berberine in preparation of antitumor drug |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107281180A (en) * | 2016-04-05 | 2017-10-24 | 西南大学 | Application of the 8- alkyl berberine salts in prevention and treatment lung-cancer medicament is prepared |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101870964A (en) * | 2010-05-25 | 2010-10-27 | 北京凯因科技股份有限公司 | Method for improving SAM synthetase expression level |
-
2011
- 2011-11-22 CN CN2011103752251A patent/CN103127102A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101870964A (en) * | 2010-05-25 | 2010-10-27 | 北京凯因科技股份有限公司 | Method for improving SAM synthetase expression level |
Non-Patent Citations (2)
| Title |
|---|
| 李波等: "小檗碱及其衍生物的研究进展", 《药学学报》 * |
| 杨勇等: "8-烷基小檗碱的合成", 《有机化学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107281180A (en) * | 2016-04-05 | 2017-10-24 | 西南大学 | Application of the 8- alkyl berberine salts in prevention and treatment lung-cancer medicament is prepared |
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Application publication date: 20130605 |