CN101318966B - Dimerized sesquiterpenoids, preparation and application thereof - Google Patents
Dimerized sesquiterpenoids, preparation and application thereof Download PDFInfo
- Publication number
- CN101318966B CN101318966B CN2008100358590A CN200810035859A CN101318966B CN 101318966 B CN101318966 B CN 101318966B CN 2008100358590 A CN2008100358590 A CN 2008100358590A CN 200810035859 A CN200810035859 A CN 200810035859A CN 101318966 B CN101318966 B CN 101318966B
- Authority
- CN
- China
- Prior art keywords
- terpene
- tuerfeng
- dimerization
- ainsliaidimer
- dimeric
- 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.)
- Expired - Fee Related
Links
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The invention belongs to the medicine technical field and in particular to a dimeric sesquiterpene compounds, a preparation method thereof and an application thereof. The dimeric sesquiterpenes compounds are dimeric ainsliaea terpene B and dimeric ainsliaea terpene C which are extracted and separated from macrocephaly ainsliaea and the chemical structural formulas of which are given; and the molecules of the dimeric sesquiterpenes compounds are receptively C30H36O7 and C30H32O8. The compounds can be used for preparing anti-inflammatory drugs and antitumor drugs.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of separation obtains from plant major part Tuerfeng two Dimerized sesquiterpenoids dimerization Tuerfeng terpene B (Ainsliaidimer B), dimerization Tuerfeng terpene C (Ainsliaidimer C) and its production and application.
Background technology
It is that one in composite family (Compositae) the broom chrysanthemum wood family (Mutisieae Cass) belongs to that Tuerfeng belongs to (Ainsliaea DC) plant, kind surplus the whole world 70, and there be 44 kind of 4 mutation in China, accounts for 37.5% of sum.The medicinal kind of Tuerfeng platymiscium is more.Be widely used in treatment flu cough breathe heavily, diseases such as rheumatic arthralgia, wound, urinary system.The Tuerfeng plant resources of China mainly is distributed in the Yangtze valley and each province, southwestern south China." Shanghai City medicinal material standard ", " Jiangxi Province's Chinese medicinal materials standard ", " Yunnan Province's drug standard ", " the Sanitation Ministry medicine standard " all record.
Chemical constitution study to the Tuerfeng platymiscium starts from the eighties in 20th century, mainly concentrates on Frangrant Ainsliaea Herb and the tool leaf Tuerfeng.It is reported that the Tuerfeng platymiscium mainly contains sesquiterpene lactones, sesquiterpene glycosides, steroidal, triterpene compound, studies show that sesquiterpene lactones has good antitumor activity.And modern pharmacology and clinical application show that this platymiscium has good anti-inflammatory action.Be blank to major part Tuerfeng (Ainsliaea macrocephala) The Chemical Constituents at present, based on above-mentioned situation, just more urgent to the chemical constitution study of major part Tuerfeng system.
The major part Tuerfeng originates in the northwestern Yunnan Province and the west and south, Sichuan, is born in hillside border, softwood forest down or in the ridge shrubbery, 2600～3100 meters of height above sea level are perennial herb." Chinese Plants will " is described in detail the morphological specificity of major part Tuerfeng.We in the hope of clear and definite its chemical ingredients, are Natural Medicine Chemistry research stockpile to gathering the chemical constitution study that has carried out system from the major part Tuerfeng in Yunnan; Discovery has the natural product of excellent activity, for follow-up deep research and development provide material base.
Summary of the invention
The object of the present invention is to provide a kind of new dimerization sesquiterpenoids natural compounds and preparation method thereof and its application in preparation anti-inflammatory, antitumor Chinese traditional medicine.
The present invention is two new Dimerized sesquiterpenoids that extraction separation obtains from major part Tuerfeng (growing in the Chinese yunnan Lijing), difference called after dimerization Tuerfeng terpene B (Ainsliaidimer B), dimerization Tuerfeng terpene C (AinsliaidimerC), its chemical structural formula is as follows:
The preparation method of above-claimed cpd is as follows:
(1) extract: with the dry herb of major part Tuerfeng, pulverize, with 80～95% alcohol reflux 1～3 time, each 1～2 hour; United extraction liquid, the extracting solution concentrating under reduced pressure becomes fluid extract, earlier with petroleum ether extraction, again with ethyl acetate extraction, obtains ethyl acetate extract behind the thin up;
(2) separate: above-mentioned ethyl acetate extract applying silicon plastic column chromatography, it with volume ratio 20: 1～4: 1 chloroform/methanol system gradient elution, thin-layer chromatography detects, collecting the flow point contain dimerization Tuerfeng terpene B and dimerization Tuerfeng terpene C respectively, again through the dextrane gel column chromatography, is 1: 1 chloroform/methanol wash-out with volume ratio, after the C18 reversed phase column chromatography, with volume ratio is that 4: 6～6: 4 methanol-water carries out wash-out, and thin-layer chromatography detects, dimerization Tuerfeng terpene B and dimerization Tuerfeng terpene C.
Dimerized sesquiterpenoids of the present invention (Ainsliaidimer) B is colourless prism, by electron spray(ES) ion massspectrum signal m/z 507[M-H]
-, high resolution mass spectrum must the accurate total mass number of this compound is 507.2376[M-H]
-, calculate that its molecular formula is C
30H
36O
7Dimerized sesquiterpenoids of the present invention (Ainsliaidimer) C is colourless prism, by electron spray(ES) ion massspectrum signal m/z 519[M-H]
-, high resolution mass spectrum must the accurate total mass number of this compound is 519.1989[M-H]
-, calculate that its molecular formula is C
30H
32O
8This compound structure is further determined by the X-diffraction.
1H and
13The C nuclear magnetic resonance data sees Table 1 and table 2.
Table 1Ainsliaidimer B's
1H and
13The C nuclear magnetic resonance data
Table 2 Ainsliaidimer C's
1H and
13The C nuclear magnetic resonance data
Embodiment
The following examples can make those skilled in the art more fully understand the present invention, but do not limit the present invention in any way.
Embodiment 1:
Major part Tuerfeng (Ainsliaea macrocephala) herb 5kg, with 80% alcohol reflux 2 times, each 2 hours, the extracting solution concentrating under reduced pressure becomes fluid extract, earlier with petroleum ether extraction,, obtain ethyl acetate extract 320g behind the thin up again with ethyl acetate extraction; Above-mentioned ethyl acetate extract mixed with 300g silica gel mix sample, the applying silicon plastic column chromatography, it with volume ratio 20: 0～4: 1 chloroform-methanol system gradient elution, thin-layer chromatography detects, collect the flow point that contains dimerization Tuerfeng terpene B and dimerization Tuerfeng terpene C respectively, again through the dextrane gel column chromatography, it with volume ratio 1: 1 chloroform-methanol wash-out, after the C18 reversed phase column chromatography, with volume ratio is that 4: 6～6: 4 methanol-water carries out wash-out, thin-layer chromatography detects, and gets the pure product 125mg of dimerization Tuerfeng terpene B (Ainsliaidimer B), the pure product 86mg of dimerization Tuerfeng terpene C (Ainsliaidimer C).
The cytotoxic activity experiment of embodiment 2:Ainsliaidimer B and Ainsliaidimer C
1, experiment material
1.1, given the test agent
After Ainsliaidimer B, Ainsliaidimer C dissolve with DMSO (Merck), add solution or uniform suspension that PBS (-) is made into 1000 μ g/ml, then with PBS (-) dilution that contains DMSO.
1.2, cell strain
A549 (human lung carcinoma cell)
LOVO (people's colon-cancer cell)
6T-CEM (human T cell leukemia cell)
HL-60 (human leukemia cell)
HepG-2 (human liver cancer cell)
1.3, nutrient solution
RPMI1640+15%NBS+ is two anti-
1.4, other materials
Full-automatic microplate reader: model: WellscanMK-2, production firm: Labsystems import 96 well culture plates etc.
2, test method
Mtt assay: it is 4～6 * 10 that the every hole of 96 orifice plates adds concentration
4The cell suspension 100 μ l of individual/ml put 37 ℃, 5%CO
2In the incubator.Behind the 24h, add sample liquid, two multiple holes are established in 10 μ l/ holes, and 37 ℃, 5%CO
2Effect 72h.Every hole adds the MTT solution 20 μ l of 5mg/ml, adds lysate behind the effect 4h, and put in the incubator in 100 μ l/ holes, and 570nm OD value is surveyed with the full-automatic microplate reader of MK-2 in the dissolving back.
3, test-results
The results are shown in Table 3, the result shows, Ainsliaidimer B and Ainsliaidimer C are to human lung carcinoma cell, people's colon-cancer cell, the human T cell leukemia cell, human leukemia cell and human liver cancer cell all have better inhibited activity, and Ainsliaidimer B, C have favorable anti-tumor effect, have the excellent development prospect.
Embodiment 3:Ainsliaidimer B and Ainsliaidimer C are to the efficacy experiment of mouse S180 sarcoma (solid-type)
1, experiment material
1.1 given the test agent
Ainsliaidimer B, Ainsliaidimer C are respectively with using the 0.5%CMC wiring solution-forming behind a small amount of tween-80 hydrotropy.
1.2 animal
Strain: Kunming mouse
The source: the The 2nd Army Medical College Experimental Animal Center provides.
Conformity certification number: Shanghai is moving closes the card word No. 107
Body weight: 18-20g
Sex: female.
1.3 transplanted tumor
Mouse S180 sarcoma is gone down to posterity by Shanghai Institute of Pharmaceutical Industry and to keep.
2, experimental technique
Get well-grown mouse S180 sarcoma ascites, dilute with 1: 4 with physiological saline, every mouse armpit subcutaneous vaccination 0.2ml, random packet is divided into control group, endoxan group (CTX group, 20mg/kg, ip * 7), administration (5mg/kg) group, next day is played administration in the inoculation back, the administration volume is the 0.5ml/20g body weight, continuous irrigation stomach 7 days.Inoculate back 10 days and take off neck execution animal, dissect behind the title the weight of animals and get the knurl piece, claim knurl heavy.The result judges according to following formula:
3, experimental result
Ainsliaidimer B, Ainsliaidimer C have significant tumor-inhibiting action.Experimental result sees Table 4.
Table 3Ainsliaidimer B and Ainsliaidimer C are to the in-vitro multiplication restraining effect of human body tumour cell
Table 4Ainsliaidimer B and Ainsliaidimer C are to the restraining effect of mouse S180 sarcoma
Compare with control group:
*P＜0.05,
*P＜0.01.
Embodiment 4:Ainsliaidimer B, Ainsliaidimer C anti-inflammatory experiment mice ear swelling model
1 laboratory animal
Swiss kind mouse, male, body weight 20-24g.
2. experimental model and testing method
Get 80 of mouse, be divided into 8 groups at random, press the dosage gastric infusion 3d shown in the table 5,1h after the last administration, dimethylbenzene with 0.05ml causes inflammation with mouse left side ear, the punch tool that with diameter is 7mm is the overlapping punching of ears, and the disk of laying is gone up weighing at torsion(type)balance (sensitivity be ten thousand/), represents its swelling degree with the weight difference of mouse ear two disks.
3 statistical study:
All experimental result is all represented with mean ± standard error.Respectively organize data and the blank significant difference of organizing with student t-check, P＜0.05, expression difference has the significance meaning.
4 test-results:
Table 5.Ainsliaidimer B, Ainsliaidimer C are to the influence of mice ear test
Compare with the blank group,
*P＜0.05,
*P＜0.01
The result shows that positive control drug hydrocortisone, Ainsliaidimer B, Ainsliaidimer C have significant inhibitory effect to the inflammation that the mice ear model causes.
Embodiment 5:Ainsliaidimer B, Ainsliaidimer C anti-inflammatory experimental rat carrageenin foot swelling model
1 laboratory animal
The SD rat, male and female dual-purpose, body weight 180-220g.
2. experimental model and testing method
Get 80 of rats, be divided into 8 groups at random, press the dosage gastric infusion 4d shown in the table 6, before the last administration, measure and cause scorching preceding volume; 30min after the last administration, the sufficient subcutaneous injection 1% carrageenin 0.1ml that wastes time causes inflammation in rat right hind leg.Respectively at cause scorching back 2,4,6h measures the following volume of right ankle joint.
3 statistical study:
All experimental result is all represented with mean ± standard error.Respectively organize data and the blank significant difference of organizing with student t-check, P＜0.05, expression difference has the significance meaning.
4 test-results:
Table 6.Ainsliaidimer B, Ainsliaidimer C are to the influence of rat angle justice dish glue foot swelling test
Compare with the blank group,
*P＜0.05,
*P＜0.01
The result shows that positive control drug dexamethasone, Ainsliaidimer B, Ainsliaidimer C have significant inhibitory effect to the caused inflammation of rat carrageenan foot swelling model.
Embodiment 6:Ainsliaidimer B, the test of Ainsliaidimer C anti-inflammatory experiment mice abdominal cavity capillary permeability
1 laboratory animal
NH is a mouse, male and female dual-purpose, body weight 18-22g.
2. experimental model and testing method
Get 80 of rats, be divided into 8 groups at random, press the dosage gastric infusion 1h shown in the table 7, tail vein injection 2% AZO-blue normal saline solution 0.1ml/10g body weight, abdominal injection 0.8% acetic acid normal saline solution 0.20ml/ only takes off cervical vertebra and puts to death mouse behind the 20min immediately, divides with 5ml physiological saline and washs the abdominal cavity for several times, 3000 rev/mins, centrifugal 15min; Getting supernatant liquor uses microplate reader in its optical density(OD) of 570nm colorimetric estimation (OD) value.
3 statistical study:
All experimental result is all represented with mean ± standard error.Respectively organize data and the blank significant difference of organizing with student t-check, P＜0.05, expression difference has the significance meaning.
4 test-results:
Table 7.Ainsliaidimer B, Ainsliaidimer C are to the influence of mouse peritoneal capillary permeability test
Compare with the blank group,
*P＜0.05,
*P＜0.01
The result shows that positive control drug dexamethasone, Ainsliaidimer B, the Ainsliaidimer C inflammation that test causes to the mouse peritoneal capillary permeability have significant inhibitory effect.
Claims (4)
1. a Dimerized sesquiterpenoids is respectively dimerization Tuerfeng terpene B and dimerization Tuerfeng terpene C, it is characterized in that chemical structural formula is as follows:
Dimerization Tuerfeng terpene B dimerization Tuerfeng terpene C.
2. the preparation method of Dimerized sesquiterpenoids as claimed in claim 1 is characterized in that concrete steps are as follows:
(1) extract: with the dry herb of major part Tuerfeng, pulverize, with 80～95% alcohol reflux 1～3 time, each 1～2 hour; United extraction liquid, the extracting solution concentrating under reduced pressure becomes fluid extract, earlier with petroleum ether extraction, again with ethyl acetate extraction, obtains ethyl acetate extract behind the thin up;
(2) separate: above-mentioned ethyl acetate extract applying silicon plastic column chromatography, it with volume ratio 20: 0～4: 1 chloroform/methanol system gradient elution, thin-layer chromatography detects, collecting the flow point contain dimerization Tuerfeng terpene B and dimerization Tuerfeng terpene C respectively, again through the dextrane gel column chromatography, is 1: 1 chloroform/methanol wash-out with volume ratio, after the C18 reversed phase column chromatography, with volume ratio is that 4: 6～6: 4 methanol-water carries out wash-out, and thin-layer chromatography detects, dimerization Tuerfeng terpene B and dimerization Tuerfeng terpene C.
3. dimeric ainsliaea terpene B according to claim 1 or the dimerization Tuerfeng terpene C application in the preparation anti-inflammatory drug.
4. dimeric ainsliaea terpene B according to claim 1 or the dimerization Tuerfeng terpene C application in the preparation antitumor drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100358590A CN101318966B (en) | 2008-04-10 | 2008-04-10 | Dimerized sesquiterpenoids, preparation and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100358590A CN101318966B (en) | 2008-04-10 | 2008-04-10 | Dimerized sesquiterpenoids, preparation and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101318966A CN101318966A (en) | 2008-12-10 |
| CN101318966B true CN101318966B (en) | 2010-12-15 |
Family
ID=40179262
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008100358590A Expired - Fee Related CN101318966B (en) | 2008-04-10 | 2008-04-10 | Dimerized sesquiterpenoids, preparation and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101318966B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106943396B (en) * | 2015-12-01 | 2018-08-24 | 哈尔滨商业大学 | The new alkali A application in preparations of anti-tumor drugs of water ghost any of several broadleaf plants |
-
2008
- 2008-04-10 CN CN2008100358590A patent/CN101318966B/en not_active Expired - Fee Related
Non-Patent Citations (2)
| Title |
|---|
| FERDINAND BOHLMANN, et al..DIMERIC GUAIANOLIDES AND OTHER CONSTITUENTS FROM GOCHNATIA SPECIES.《Phytochemistry》.1986,第25卷(第5期),第1175-1178页. * |
| FERDINAND BOHLMANN, et al..DIMERIC SESQUITERPENE LACTONES AND KOLAVANE DERIVATIVES FROM GOCHNATIA PANICULATA.《Phytochemistry》.1983,第22卷(第1期),第191-195页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101318966A (en) | 2008-12-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1307131C (en) | Antineoplastic extract of Chinese fan palm and its preparation method and uses | |
| CN103316096A (en) | General flavone extract of seeds of nigella damascena l., nigella sativa l. or nigella glandulifera freyn et sint., and preparation method and use thereof | |
| CN104311623B (en) | A kind of Sasanguasaponin C by name 1with Sasanguasaponin C 2pentacyclic triterpenoid and preparation method thereof and application | |
| CN101830875A (en) | Anti-inflammatory compound inula lineariifolia lactone A and preparation method and application thereof | |
| CN101318946B (en) | Dimeric ainsliaea terpene A, preparation and application thereof | |
| CN102068584B (en) | A kind of Dioscorea zingiberensis hydrophobicity steroidal saponin extract and its production and use | |
| CN101284835B (en) | Dimeric sesquiterpene lactone compounds, preparation method and applications thereof | |
| CN101028322B (en) | Use of Maoliefengdou extract for preparing anti-cancer medicine | |
| CN106943396B (en) | The new alkali A application in preparations of anti-tumor drugs of water ghost any of several broadleaf plants | |
| CN102030800B (en) | Abies holophylla triterpenoid compound, extraction separation thereof and application thereof | |
| CN101318966B (en) | Dimerized sesquiterpenoids, preparation and application thereof | |
| CN100590119C (en) | Antineoplastic compound of red pineapple flower alkali A, preparation method and application thereof | |
| CN101926921A (en) | Liriope muscari total saponin and preparation method thereof | |
| CN101565443B (en) | New fir triterpene lactone compound, preparation method and application thereof | |
| CN105418722B (en) | A kind of entitled Sasanguasaponin C4And C5Pentacyclic triterpenoid preparation method | |
| CN103893412A (en) | Anti-tumor callicarpa nudiflora extract and preparation method and application thereof | |
| CN102085293B (en) | Liriope muscari extract with anti-tumor action and preparation method thereof | |
| CN101284833B (en) | Compound bi-inulicin 4, preparation method and applications thereof | |
| CN101284004B (en) | Application of two bi-sesquiterpenes compound for preparing antineoplastic and antiinflammatory medicine | |
| CN109705183A (en) | Smelly seven secondary metabolites and its pharmaceutical composition and preparation method and its application | |
| CN103694302B (en) | 2 α, the preparation method of 3 beta-dihydroxyl-30-olea-12,20 (29)-diene-28-acid and preparing the application in antitumor drug | |
| CN103263409A (en) | Application of bixanthone compound FLBG-1108 or its pharmaceutical salts in preparation of anti-cancer drugs | |
| CN102440985A (en) | Application of bixanthone compound FLBG-1108 or its medicinal salt in preparing anticancer medicaments | |
| CN109206392A (en) | A kind of coumarin kind compound and the preparation method and application thereof | |
| CN103393637A (en) | Use of flavonoid compound in preparation of metabolic disease resistance medicines |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20101215 Termination date: 20170410 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |