CN103127062A - Application of 13'-acetyl silver grass alcohol C in manufacturing of antineoplastic drugs - Google Patents
Application of 13'-acetyl silver grass alcohol C in manufacturing of antineoplastic drugs Download PDFInfo
- Publication number
- CN103127062A CN103127062A CN2011103869918A CN201110386991A CN103127062A CN 103127062 A CN103127062 A CN 103127062A CN 2011103869918 A CN2011103869918 A CN 2011103869918A CN 201110386991 A CN201110386991 A CN 201110386991A CN 103127062 A CN103127062 A CN 103127062A
- Authority
- CN
- China
- Prior art keywords
- shizukaol
- cell
- acetyl
- acetyl group
- application
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the field of chemical industry and medicines, and relates to application of 13'-acetyl silver grass alcohol C in manufacturing of antineoplastic drugs. According to the application of the 13'-acetyl silver grass alcohol C in the manufacturing of the antineoplastic drugs, cancer cells comprise hepatoma carcinoma cells, leukemia cells, gastric carcinoma cells and pancreatic cancer cells. The 13'-acetyl silver grass alcohol C belongs to natural products, is small in toxic and side effects, high in biological utilization rate and stable in properties, and has clinical application value. Small molecule compounds of the 13'-acetyl silver alcohol C are used as new antineoplastic drugs or used as auxiliary components for developing, are significant in tumor suppression effect, environmental-protecting, and capable of providing a new approach and means for curing and treatment of tumors.
Description
Technical field
The invention belongs to chemical field and field of medicaments, relate to the application of 13 '-acetyl group shizukaol C in the preparation antitumor drug.
Background technology
Herba chloranthi japonici is herb or the root and rhizome of Chloranthaceae plant Herba chloranthi japonici (Chloranthus Japonicus Sieb).Sesquiterpenoids is a compounds important in the Chloranthaceae plant, in whole Chloranthaceae plant, distribution is arranged all, has the biological activitys such as antiinflammatory spasmolytic, inhibition microorganism.Obtain half its skeleton of terpenoid complex structure in Herba chloranthi japonici and can be divided into a few types such as eudesmane type, ring eudesmane-type, germacrane, acorane type, they have the various ways such as lactone, ketone, alcohol, polymer simultaneously.
2008; Yang etc. extract from the plant of full edge chu lan tree (also have and be called the floating and thready pulse chu lan tree) and have obtained 13 '-acetyl group shizukaol C; and think that it may be that the blocking agent of potassium-channel (is the compound 2 in literary composition; Chlorahololides C-F:a new class of potent and selective potassium channel blockers from Chloranthus holostegius.; Tetrahedron; 64 (9), 2027-2034., 2008).2009; Lee etc. have leniently extracted 13 '-acetyl group shizukaol C in leaf Chloranthus spicatus; analyzed the structure of this compound; and prove by experiment its have antifungic action (be the CHE-23C in literary composition, Antifungal Activity of CHE-23C, a Dimeric Sesquiterpene from Chloranthus henryi.; Journal of Agricultural and Food Chemistry; 57 (13), 5750-5755., 2009).But, still belong to minority about the function report of 13 '-acetyl group shizukaol C, need further to explore.
13 '-acetyl group shizukaol C is natural product, and bioavailability is higher, character is more stable, has clinical use value.To going deep into that the chemistry and biology of this compounds 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 13 '-acetyl group shizukaol C.
The invention provides the application of 13 '-acetyl group shizukaol C 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, 13 '-acetyl group shizukaol C 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 13 '-acetyl group shizukaol C is 1-100 μ M.For example, 1-2 μ M, 1-10 μ M, 1-5 μ M, 5-20 μ M, 2-30 μ M, 5-60 μ M, 5-90 μ M, 10-80 μ M, 10-50 μ M, 10-60 μ M, 10-20 μ M, 10-30 μ M, 1-60 μ M, 5-10 μ M, etc.
The present invention also provides a kind of antitumor drug, and the active component of described antitumor drug is 13 '-acetyl group shizukaol C.Described tumor can be hepatocarcinoma, gastric cancer, 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 13 '-acetyl group shizukaol C 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 13 '-acetyl group shizukaol C 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.13 '-acetyl group shizukaol C 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, 13 '-acetyl group shizukaol C of the present invention also can use together with the other treatment agent.
When 13 '-acetyl group shizukaol C of the present invention is used as medicine; 13 '-acetyl group shizukaol C 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 13 '-acetyl group shizukaol C in the preparation antitumor drug.13 '-acetyl group shizukaol C 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 A549 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 25cm2 goes down to posterity in the culture bottle of a 75cm2.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 * 107/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:
13 '-acetyl group shizukaol C is dissolved in DMSO (dimethyl sulfoxide), and the mother solution that is mixed with 100mM or 50mM is standby.
Embodiment 1MTS method is measured 13 '-acetyl group shizukaol C to the growth inhibited effect of hepatoma carcinoma cell
HepG2 (available from ATCC) 3 * 103/ holes are seeded to 96 orifice plates, cultivate to make it in 24 hours to add 13 '-acetyl group shizukaol C (available from Shanghai Pharmaceutical Inst., Chinese Academy of Sciences) after adherent, establish 6 Concentraton gradient, and each concentration is established 3 multiple holes.Cell is cultivated after 72 hours under the 5%CO2 condition at 37 ℃, outwells culture fluid, measures 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 13 '-acetyl group shizukaol C to the IC50 value of HepG2 cell.
IC50 refers to the concentration of a suppressed half inhibitor.Here be the concentration of the half 13 ' that the HepG2 cell quantity is contrast-acetyl group shizukaol C.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: 13 '-acetyl group shizukaol C is 103 μ M to the IC50 value of HepG2 cell.
The growth inhibited effect of embodiment 213 '-acetyl group shizukaol C 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 * 103.
2) treat adherent, the rear dosing of spending the night, dosing (13 '-acetyl group shizukaol C 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: 13 '-acetyl group shizukaol C is 5.38 μ M to the IC50 value of PANC-1 cell.
The growth inhibited effect of embodiment 313 '-acetyl group shizukaol C to the human leukemia cell
Method according to embodiment 2 detects 13 '-acetyl group shizukaol C to the effect of K562, and result shows that 13 '-acetyl group shizukaol C is 1.75 μ M to the IC50 value of K562 cell.
The growth inhibited effect of embodiment 413 '-acetyl group shizukaol C to gastric carcinoma cells
Method according to embodiment 2 detects 13 '-acetyl group shizukaol C to the effect of HGC, and result shows that 13 '-acetyl group shizukaol C is 9.68 μ M to the IC50 value of HGC cell.
Claims (10)
1.13 the application of '-acetyl group shizukaol C in the preparation antitumor drug.
2. application as claimed in claim 1, is characterized in that, described tumor is hepatocarcinoma, gastric cancer, leukemia or cancer of pancreas.
3. application as claimed in claim 1, is characterized in that, described antitumor drug is anti-gastric cancer 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, 13 '-acetyl group shizukaol C added in the culture fluid of tumor cell.
7. method as claimed in claim 6, is characterized in that, described tumor cell is stomach cancer cell or pancreatic cancer cell.
8. method as claimed in claim 6, is characterized in that, the final concentration that adds 13 '-acetyl group shizukaol C is 1-100 μ M.
9. an antitumor drug, is characterized in that, the active component of described antitumor drug is 13 '-acetyl group shizukaol C.
10. antitumor drug as claimed in claim 9, is characterized in that, described tumor is gastric cancer or cancer of pancreas.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103869918A CN103127062A (en) | 2011-11-28 | 2011-11-28 | Application of 13'-acetyl silver grass alcohol C in manufacturing of antineoplastic drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103869918A CN103127062A (en) | 2011-11-28 | 2011-11-28 | Application of 13'-acetyl silver grass alcohol C in manufacturing of antineoplastic drugs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103127062A true CN103127062A (en) | 2013-06-05 |
Family
ID=48487937
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011103869918A Pending CN103127062A (en) | 2011-11-28 | 2011-11-28 | Application of 13'-acetyl silver grass alcohol C in manufacturing of antineoplastic drugs |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103127062A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105213369A (en) * | 2014-07-03 | 2016-01-06 | 复旦大学 | Shizukaol D is preparing the application in Hepatoma therapy medicine |
| CN105267206A (en) * | 2014-07-03 | 2016-01-27 | 复旦大学 | Application of ShizukaolD in preparing medicine for inhibiting clone formation of hepatoma carcinoma cells |
-
2011
- 2011-11-28 CN CN2011103869918A patent/CN103127062A/en active Pending
Non-Patent Citations (4)
| Title |
|---|
| XIA-CHANG WANG ET AL.: "Lindenane Sesquiterpene Dimers from Chloranthus fortunei", 《J.NAT.PROD》 * |
| YUN MI LEE ET AL.: "Antifungal Activity of CHE-23C,a Dimeric Sesquiterpene from Chloranthus henyri", 《J.AGRIC.FOOD CHEM》 * |
| ZHA-JUN ZHAN ET AL.: "Natural disesquiterpenoids", 《NAT. PROD. REP.》 * |
| 曹聪等: "金粟兰属植物的化学成分和药理作用研究进展", 《中国中药杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105213369A (en) * | 2014-07-03 | 2016-01-06 | 复旦大学 | Shizukaol D is preparing the application in Hepatoma therapy medicine |
| CN105267206A (en) * | 2014-07-03 | 2016-01-27 | 复旦大学 | Application of ShizukaolD in preparing medicine for inhibiting clone formation of hepatoma carcinoma cells |
| CN105213369B (en) * | 2014-07-03 | 2018-07-24 | 复旦大学 | Shizukaol D is preparing the application in treating liver-cancer medicine |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102526073A (en) | Application of mogrol H9 for preparing antitumor drugs | |
| CN103127060A (en) | Application of chloranthus japonicus alcohol D in preparation of antitumor drugs | |
| CN103127049A (en) | Application of usnic acid in manufacturing antitumor drugs | |
| CN103127061A (en) | Medicine application of chloranthus japonicus alcohol M | |
| CN103127063A (en) | Application of chloranthus japonicus alcohol F in preparation of antitumor drugs | |
| CN103202834A (en) | Applications of oridonin in the preparation of antineoplastic drugs | |
| CN103127062A (en) | Application of 13'-acetyl silver grass alcohol C in manufacturing of antineoplastic drugs | |
| CN103417536B (en) | The application in antitumor drug prepared by harmol | |
| CN102397280B (en) | Application of 2 alpha-hydroxy protopanoxadiol medicine | |
| CN103099805A (en) | Application of isosteviol derivative H14 in preparation of antitumor medicaments | |
| CN102366416B (en) | Pharmaceutical application of 12-dehydroxy-21-hydroxy protopanoxadiol | |
| CN103054851A (en) | Application of chloranthalactone C in preparation of anti-tumor medicament | |
| CN102488677B (en) | Application of thelephora ganbajun in preparation of antitumor drugs | |
| CN103417527A (en) | Medical uses of methyl (E)-3-[2-(4-hydroxy-3-methoxyphenyl)-3-hydroxymethyl-7-methoxy-2,3-dihydro-1-benzofuran-5-yl]-prop-2-enoate | |
| CN103083330B (en) | Application of solasodine in preparing antitumor medicines | |
| CN103127039A (en) | Application of magnolol in preparation of antitumor drug | |
| CN103099804A (en) | Application of isosteviol lactone in preparation of antitumor medicaments | |
| CN103127103A (en) | Application of sophoridine in anti-tumor drug preparation | |
| CN103127057A (en) | Application of fraxinellone in preparing of antineoplastic medicines | |
| CN103127051A (en) | Application of curcumenol in anti-tumor drug preparation | |
| CN103127056A (en) | Application of psoromic acid in anti-tumor drug preparation | |
| CN103083329B (en) | Application of picriafel-terrae 1 in anti-tumor drug preparation | |
| CN103083331B (en) | Application of solanum laciniatum ketene in preparing antitumor medicines | |
| CN102366417A (en) | Application of protopanoxadiol in preparation of antitumor medicaments | |
| CN105267201A (en) | Application of oridonin in preparing medicine for treating tumour |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20130605 |