CN103127103A - Application of sophoridine in anti-tumor drug preparation - Google Patents
Application of sophoridine in anti-tumor drug preparation Download PDFInfo
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- CN103127103A CN103127103A CN2011103795134A CN201110379513A CN103127103A CN 103127103 A CN103127103 A CN 103127103A CN 2011103795134 A CN2011103795134 A CN 2011103795134A CN 201110379513 A CN201110379513 A CN 201110379513A CN 103127103 A CN103127103 A CN 103127103A
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Abstract
The invention belongs to the field of chemical engineering and medicine, and relates to an application of sophoridine in anti-tumor drug preparation. The present invention provides an application of sophoridine in anti-tumor drug preparation, wherein tumor cells comprise leukemia cells and pancreatic cancer cells. The sophoridine belongs to natural products, and has characteristics of low toxic-side effect, high bioavailability, stable property, and clinical use value. With application of the small molecule compound as a new anti-tumor drug or an auxiliary component thereof to be developed, advantages of significant tumor inhibition effect and green environmental protection are provided, and a new way is provided for treatment and cure of tumors.
Description
Technical field
The invention belongs to chemical field and field of medicaments, relate to the application of sophoridine in the preparation antitumor drug.
Background technology
Sophoridine, English name are Sophoridine.Be the crystallization of white bodkin shape or large prism-shaped crystallization (petroleum ether), bitter in the mouth, 108～109 ° of fusing points, (α) D-63.45 ° (c=0.9879, water), and soluble in water, methanol, ethanol, carbon tetrachloride etc.Colourless acicular crystal (normal hexane), 109 ° of fusing points, (α) 22D-61.6 ° (c=0.44, ethanol); IR γ KBr max cm-1:2800,2750 (trans quinoline promise Li Xiding), 1620 (lactams c=O); MSm/e (%): 248 (M+, 74), 247 (100), 205 (35), 150 (56), 96 (78); CNMR (CDCl3) δ: 169.8 (s), 63.3 (d), 55.8 (t), 55.7 (d), 50.2 (t), 47.5 (t), 40.9 (d), 32.5 (t), 30.7 (d), 30.2 (t), 28.1 (t), 23.7 (t), 21.8 (t), 21.5 (t), 18.9 (t).Structural formula is:
After the sophoridine intravenous injection, can cause that blood pressure falls after rising; Isolated heart to homoiothermy, cold blooded animal has excited the work
With; Can cause contraction to tip and visceral vessel.Extract this product of gained from Sophora Alopecuroides L., through the clinical observation therapeutic equivalence, effect is slight.Extracorporeal bacteria inhibitor test proves that 15 kinds of dysentery bacterial strains such as will Hayes, Song Nei Shi, Fu Shi, this Mi Shi are all had inhibitory action.
Sophoridine belongs to natural product, and toxic and side effects is less, bioavailability is high, stable in properties, has clinical use value preferably.But, not yet relevant for sophoridine in the play-by-play for the treatment of aspect tumor.
Summary of the invention
The new medicinal usage that the purpose of this invention is to provide sophoridine.
The invention provides the application of sophoridine in the preparation antitumor drug.Described antitumor drug is injection or tablet.Described antitumor drug can be anti-cancer of pancreas medicine or anti-leukemia medicine.This antitumor drug can be injection or tablet.
The invention provides a kind of method that suppresses tumor cell in vitro propagation, sophoridine is added in the culture fluid of tumor cell.Described tumor cell is leukaemia or pancreatic cancer cell.Generally speaking, adding the final concentration of sophoridine is 1-100 μ M.For example, 1-5 μ M, 1-10 μ M, 1-20 μ M, 1-30 μ M, 1-50 μ M, 3-60 μ M, 3-50 μ M, 3-30 μ M, 3-20 μ M, 3-10 μ M, 3-5 μ M, 5-20 μ M, etc.
The present invention also provides a kind of antitumor drug, and the active component of described antitumor drug is sophoridine.Described tumor can be cancer of pancreas or leukemia.
Micromolecular compound of the present invention can adopt the preparation method preparation of various routines.For example, adopt the synthetic method of artificial chemistry.Sophoridine in the embodiment of the present invention is available from Shanghai Pharmaceutical Inst., Chinese Academy of Sciences.
Utilize micromolecular compound of the present invention, by various conventional screening techniques, can filter out and the interactional material of sophoridine generation, as receptor, inhibitor or antagonist etc.
The present invention and inhibitor, antagonist 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 sophoridine 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.Sophoridine 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, sophoridine of the present invention also can use together with the other treatment agent.
When sophoridine of the present invention is used as medicine, the sophoridine 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 sophoridine in the preparation antitumor drug.Sophoridine 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.Cell culture contains 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 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.
Embodiment 1MTS method is measured sophoridine to the growth inhibited effect of pancreatic cancer cell
PANC-1 cell (available from ATCC) 3 * 10
3/ hole is seeded to 96 orifice plates, cultivates to make it in 24 hours to add sophoridine (available from Shanghai Pharmaceutical Inst., Chinese Academy of Sciences) after adherent, establishes 5 Concentraton gradient, and each concentration is established 3 multiple holes.Adding consistency is respectively 50,16.67,5.56,1.85,0.62 μ M.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 sophoridine to the IC50 value of PANC-1 cell.
IC50 refers to a suppressed half
InhibitorConcentration.Here be the PANC-1 cell quantity and be the concentration of a half sophoridine of contrast.
Result: sophoridine is about 92.32 μ M to the IC50 value of PANC-1 cell.
The growth inhibited effect of embodiment 2 sophoridine to human pancreatic cancer cell
Utilize cck-8 test kit (Japanese colleague's chemistry institute) to detect.
Step:
1) K562 cell (available from ATCC) is planted in 96 orifice plates uniformly, every porocyte number is 10000.
2) treat adherent, the rear dosing of spending the night, adding consistency is respectively 50,16.67,5.56,1.85,0.62 μ M, each concentration has 3 multiple holes.
3) cultivated 48 hours, complete medium is replaced to the mixture (10: 1) of serum-free medium and CCK8, hatched 2 hours in 37 ℃ of incubators.
4) take 450nm as measuring wavelength, take 650nm as the contrast wavelength, measure reading on microplate reader.
Result: sophoridine is 1.73 μ M to the IC50 value of K562 cell.
Claims (10)
1. the application of sophoridine in the preparation antitumor drug.
2. application as claimed in claim 1, is characterized in that, described tumor is leukemia or cancer of pancreas.
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, described antitumor drug is anti-cancer of pancreas medicine.
5. application as claimed in claim 1, is characterized in that, the dosage form of described antitumor drug is injection, tablet or capsule.
6. a method that suppresses tumor cell in vitro propagation, is characterized in that, sophoridine added in the culture fluid of tumor cell.
7. method as claimed in claim 6, is characterized in that, described tumor cell is leukemia or pancreatic cancer cell.
8. method as claimed in claim 6, is characterized in that, the final concentration that adds sophoridine is 1-100 μ M.
9. an antitumor drug, is characterized in that, the active component of described antitumor drug is sophoridine.
10. antitumor drug as claimed in claim 9, is characterized in that, described tumor is leukemia or cancer of pancreas.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103795134A CN103127103A (en) | 2011-11-24 | 2011-11-24 | Application of sophoridine in anti-tumor drug preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103795134A CN103127103A (en) | 2011-11-24 | 2011-11-24 | Application of sophoridine in anti-tumor drug preparation |
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| Publication Number | Publication Date |
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| CN103127103A true CN103127103A (en) | 2013-06-05 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2011103795134A Pending CN103127103A (en) | 2011-11-24 | 2011-11-24 | Application of sophoridine in anti-tumor drug preparation |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104230931A (en) * | 2013-06-19 | 2014-12-24 | 天士力控股集团有限公司 | Sophoridine derivatives, and preparation method and application thereof |
| CN104250247A (en) * | 2013-06-28 | 2014-12-31 | 中国医学科学院医药生物技术研究所 | Novel sophoridine derivative sophoridine acid, sophoridine alcohol, sophoridine ester and sophoridine ether, preparation method and use thereof |
-
2011
- 2011-11-24 CN CN2011103795134A patent/CN103127103A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| 李雪梅等: "抗癌新药槐定碱的基础研究", 《2006第四届中国肿瘤学术大会论文集》 * |
| 杨泽云等: "槐定碱药理作用研究进展", 《九江学院学报（自然科学版）》 * |
| 王秀坤等: "白刺花生物碱的体外抑瘤作用", 《北京中医药大学学报》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104230931A (en) * | 2013-06-19 | 2014-12-24 | 天士力控股集团有限公司 | Sophoridine derivatives, and preparation method and application thereof |
| CN104250247A (en) * | 2013-06-28 | 2014-12-31 | 中国医学科学院医药生物技术研究所 | Novel sophoridine derivative sophoridine acid, sophoridine alcohol, sophoridine ester and sophoridine ether, preparation method and use thereof |
| CN104250247B (en) * | 2013-06-28 | 2016-10-12 | 中国医学科学院医药生物技术研究所 | Novel sophoridine analog derivative Chinese scholartree determines acid, Chinese scholartree determines alcohol, Chinese scholartree determines ester, Chinese scholartree determines ether and its production and use |
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Application publication date: 20130605 |