CN103127056A - Application of psoromic acid in anti-tumor drug preparation - Google Patents
Application of psoromic acid in anti-tumor drug preparation Download PDFInfo
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- CN103127056A CN103127056A CN2011103795149A CN201110379514A CN103127056A CN 103127056 A CN103127056 A CN 103127056A CN 2011103795149 A CN2011103795149 A CN 2011103795149A CN 201110379514 A CN201110379514 A CN 201110379514A CN 103127056 A CN103127056 A CN 103127056A
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Abstract
The invention belongs to the field of chemical engineering and medicine, and relates to an application of psoromic acid in anti-tumor drug preparation. The present invention provides an application of psoromic acid in anti-tumor drug preparation, wherein tumor cells comprise liver cancer cells, leukemia cells and pancreatic cancer cells. The psoromic acid 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 psoromic acid in the preparation antitumor drug.
Background technology
Psoromic acid, molecular formula are C18H1408, and No. CAS is 7299-11-8, and structural formula is as follows:
As far back as nineteen sixty-five, Arshad etc. just mention psoromic acid (Buffer action of saponins.I.Analytical studies., Journal of Scientific and Industrial Research, 8 (3) in its article, 99-102., 1965).
1973, KRAJNIA etc. have reported that the method for extracting psoromic acid from Australian Pericarpium Zanthoxyli (AUSTRALIAN ZANTHOXYLUM) (is the psoromic acid in literary composition, Chemical constituents of Australian Zanthoxylum species.VI.Examination of the constituents of the bark of Zanthoxylum conspersipunctatum (Rutaceae)., Australian Journal of Chemistry, 26 (3), 687-9., 1973).Also report, can separate obtaining psoromic acid from the acetone extract of Lethariella cladonioides (Lethariella cladonioides).
2002, Yuan etc. detected by the QSAR method, think that this compound has the effect of Inhibition of HIV-1 integrase (QSAR studies of HIV-1 integrase inhibition., Bioorganic﹠amp; Medicinal Chemistry, 10 (12), 4169-4183., 2002).
Psoromic acid is natural product, and bioavailability is higher, character is more stable, has clinical use value.To going deep into that this type of alkaloidal chemistry and biology is studied, its molecular mechanism of action will be progressively clear and definite along with people, and this chemical constitution that will further promote this compounds is modified and structure activity study, and helps to improve the medical value of this compounds.
Summary of the invention
The new medicinal usage that the purpose of this invention is to provide psoromic acid.
The invention provides the application of psoromic acid in the preparation antitumor drug.Described antitumor drug can be anti-hepatocarcinoma, leukemia, cancer of pancreas or gastric cancer medicine.
This antitumor drug can be injection or tablet.
The invention provides a kind of method that suppresses tumor cell in vitro propagation, psoromic acid is added in the culture fluid of tumor cell.Described tumor cell can be hepatoma carcinoma cell, blood cell, cervical cancer cell, breast cancer cell or pancreatic cancer cell.The hepatoma carcinoma cell that adopts in one embodiment of the present of invention is HepG2.Generally speaking, adding the final concentration of psoromic acid is 0.5-100 μ M.For example, 0.5-2 μ M, 0.5-10 μ M, 0.5-5 μ M, 3-20 μ M, 0.5-70 μ M, 3-60 μ M, 3-90 μ M, 10-80 μ M, 1-50 μ M, 1-60 μ M, 1-20 μ M, 10-30 μ M, 0.5-60 μ M, 3-10 μ M, etc.
The present invention also provides a kind of antitumor drug, and the active component of described antitumor drug is psoromic acid.Described tumor can be hepatocarcinoma, 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.
Utilize micromolecular compound of the present invention, by various conventional screening techniques, can filter out and the interactional material of psoromic acid 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 psoromic acid 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.Psoromic acid 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, psoromic acid of the present invention also can use together with the other treatment agent.
When psoromic acid of the present invention is used as medicine, the psoromic acid 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 psoromic acid in the preparation antitumor drug.Psoromic acid is natural product, and side effect is less, 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 QGY and HepG2 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 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. medicine is prepared:
Psoromic acid is dissolved in DMSO (dimethyl sulfoxide), and the mother solution that is mixed with 100mM or 50mM is standby.
Embodiment 1MTS method is measured psoromic acid to the growth inhibited effect of hepatoma carcinoma cell
HepG2 (available from ATCC) 3 * 10
3/ hole is seeded to 96 orifice plates, cultivates to make it in 24 hours to add psoromic acid (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 psoromic acid to the IC50 value of HepG2 cell.
IC50 refers to the concentration of a suppressed half inhibitor.Here be the HepG2 cell quantity and be the concentration of a half psoromic acid 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: psoromic acid is 0.91 μ M to the IC50 value of HepG2 cell.
Detect according to the method described above the QGY cell, psoromic acid is 0.96 μ M to the IC50 value of QGY cell as a result.
The growth inhibited effect of embodiment 2 psoromic acids to human pancreatic cancer cell
Utilize cck-8 test kit (Japanese colleague's chemistry institute) to detect.
Step:
1) PANC-1 cell (available from Chinese Academy of Sciences's cell bank) is planted in 96 orifice plates uniformly, every porocyte number is 3*10
3Individual.
2) treat adherent, the rear dosing of spending the night, dosing (psoromic acid concentration 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: psoromic acid is 3.2 μ M to the IC50 value of PANC-1 cell.
The growth inhibited effect of embodiment 3 psoromic acids to the human leukemia cell
Method according to embodiment 2 detects psoromic acid to the effect of K562, and result shows that psoromic acid is 63.77 μ M to the IC50 value of K562 cell.
Claims (10)
1. the application of psoromic acid in the preparation antitumor drug.
2. application as claimed in claim 1, is characterized in that, described tumor is hepatocarcinoma, leukemia or cancer of pancreas.
3. application as claimed in claim 1, is characterized in that, described antitumor drug is medicines resistant to liver cancer.
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, psoromic acid added in the culture fluid of tumor cell.
7. method as claimed in claim 6, is characterized in that, described tumor cell is hepatoma carcinoma cell or pancreatic cancer cell.
8. method as claimed in claim 6, is characterized in that, the final concentration that adds psoromic acid is 0.5-100 μ M.
9. an antitumor drug, is characterized in that, the active component of described antitumor drug is psoromic acid.
10. antitumor drug as claimed in claim 9, is characterized in that, described tumor is hepatocarcinoma or cancer of pancreas.
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| CN2011103795149A CN103127056A (en) | 2011-11-24 | 2011-11-24 | Application of psoromic acid in anti-tumor drug preparation |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105769850A (en) * | 2016-03-30 | 2016-07-20 | 苏州勤浩药物研究开发有限公司 | Application of psoromic acid in preparation of medicine for treating brain glioma and acute myeloid leukemia |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101687886A (en) * | 2007-05-29 | 2010-03-31 | 中国科学院上海药物研究所 | Compounds with 7-member cycle and the pharmaceutical use thereof for preventing and treating diabetes and metabolism syndrome |
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2011
- 2011-11-24 CN CN2011103795149A patent/CN103127056A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101687886A (en) * | 2007-05-29 | 2010-03-31 | 中国科学院上海药物研究所 | Compounds with 7-member cycle and the pharmaceutical use thereof for preventing and treating diabetes and metabolism syndrome |
Non-Patent Citations (1)
| Title |
|---|
| 魏江春: "《中国药用地衣》", 30 November 1982, article "中国药用地衣" * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105769850A (en) * | 2016-03-30 | 2016-07-20 | 苏州勤浩药物研究开发有限公司 | Application of psoromic acid in preparation of medicine for treating brain glioma and acute myeloid leukemia |
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Application publication date: 20130605 |