CN105541631B - Raw element A (spiratisanin A) of meadow sweet Ah Ti and preparation method thereof and the application on medicine - Google Patents
Raw element A (spiratisanin A) of meadow sweet Ah Ti and preparation method thereof and the application on medicine Download PDFInfo
- Publication number
- CN105541631B CN105541631B CN201510700064.7A CN201510700064A CN105541631B CN 105541631 B CN105541631 B CN 105541631B CN 201510700064 A CN201510700064 A CN 201510700064A CN 105541631 B CN105541631 B CN 105541631B
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- meadow sweet
- elution
- medicine
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/612—Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety
- C07C69/618—Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety having unsaturation outside the six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides a kind of raw element A (spiratisanin A) (compound of formula I) of new meadow sweet Ah Ti with medical value, and the method that the compounds of this invention is extracted from pink blossom meadow sweet (Spiraea japonica) plant, a kind of pharmaceutical composition for treating and preventing tumour by active component of compound of formula I, and the application of the compound and its pharmaceutical composition in terms of the medicine for treating and preventing tumour is prepared are provided simultaneously.
Description
Technical field
The invention belongs to medical compounds and field of pharmacology, in particular it relates to a kind of new compound meadow sweet Ah replacing
Raw element A (spiratisanin A), its preparation method, using the compound as the pharmaceutical composition of active component, and the chemical combination
The application of thing and its pharmaceutical composition in terms of the medicine for the treatment of tumour is prepared.
Background technology
Pink blossom meadow sweet (Spiraea japonica) is that the rose family (Rosaceae) Spiraea (Spiraea) uprightly fills
Wood is high up to 1.5 meters;Japan and the Korea peninsula are originated in, there is introducing and planting Chinese the greater part.The Characteristic chemical of the plant into
It is divided into diterpene-kind compound
Tumour refers to cell under the effect of tumorigenesis factor, and gene changes, and loses the normal regulation of cell growth, leads
Cause paraplasm.Tumour can be divided into the benign and malignant major class of tumour two, and the latter's growth is rapid, can be transferred to other body parts,
Destroy normal organ 26S Proteasome Structure and Function, life-threatening.
Treatment means to tumour mainly include surgical operation, radiotherapy, chemotherapy.In recent years as nano molecular is cured
With Protocols in Molecular Biology advance by leaps and bounds, the elaboration of elaboration of tumour mechanism, the searching of anti-tumor target, new antitumoral medicine
The exploitation of thing and the innovation for the treatment of means and integrated use have significant progress, and tumor patient life span is substantially prolonged
It is long.But, the seriously treatment of the solid tumor for accounting for malignant tumour more than 90% of threat human life and health not yet reaches satisfied
Curative effect, still has massive tumor patient because ultimately resulting in Endodontic failure to treating reactionless or resistance.Thus, it is found that and developing new
Type antineoplastic is still the problem of people will persistently face.
The raw element A (spiratisanin of formula (I) compound meadow sweet Ah Ti involved in the present invention are had no in the prior art
) and its report as active ingredient in terms of tumour is treated, and the compound has the report of antitumor activity A.
The content of the invention
It is an object of the invention to provide a kind of raw element A (spiratisanin of meadow sweet Ah Ti with medical value
A)。
Extracted it is a further object of the present invention to provide one kind from pink blossom meadow sweet (Spiraea japonica) plant
The method of the compounds of this invention.
The further object of the present invention be to provide it is a kind of by active component of compound of formula I be used for treat and prevent tumour
Pharmaceutical composition, and the application of the compound and composition in terms of the medicine for the treatment of tumour is prepared.
To achieve these goals, the invention provides following technical scheme:
Medicine for treating tumour, wherein containing treatment anti-tumor effective amount compound of formula I and pharmaceutical acceptable carrier and/or
Excipient.
The compounds of this invention meadow sweet Ah Ti is raw, and element A (spiratisanin A) can be converted into pharmaceutically acceptable spread out
It is biological.Such as reacted by ester hydrolysis, remove cinnamoyl, obtain compound parent nucleus, or continue to introduce other on parent nucleus
Chemical group (such as coumaric acyl, asafoetide acyl group, different asafoetide acyl group);Hydroxyl can be acylated using known method (such as formylated,
Acetylation, benzoylation, sulfonylation), halogenation, oxidation or dehydration introduce double bond.
When the compounds of this invention is used as on medicine, can directly it use, or used in the form of pharmaceutical composition.The medicine
Compositions contain 0.1~99%, preferably 0.5~90% the compounds of this invention, and remaining is pharmaceutically acceptable salt,
Or to the nontoxic and inert pharmaceutical acceptable carrier of humans and animals and/or excipient.
Described pharmaceutical carrier or excipient be it is one or more selected from solid, semi-solid and liquid diluent, filler with
And pharmaceutical preparation assistant agent.Described pharmaceutical composition is used in the form of per weight dose.The medicine of the present invention can be through
Oral and two kinds of form administrations of injection (intravenous, intramuscular injection).
It orally can use its solid or liquid preparation, such as pulvis, tablet, sugar-coat agent, capsule, solution, syrup, pill.
Injection can use its solid or liquid preparation, such as powder-injection, solution type injection.
Essence for a better understanding of the present invention, below by with the present invention compound of formula I bioactivity result come
Illustrate its application in field of medicaments.
Mtt assay cytoactive detection:
MTT full name are 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium
Bromide, is a kind of dyestuff of yellow color.Succinate dehydrogenase can be metabolized reduction MTT in living cells mitochondria, while thin
In the presence of Cytochrome C, (content of Formazan) , formazans can use enzyme to blue (or bluish violet) the water insoluble formazans of generation
Mark instrument is measured at 570nm., formazan growing amounts are directly proportional to viable count under normal conditions, therefore can be close according to light
Degree OD values deduce the number of living cells.
Experimental method:
1. inoculating cell:Individual cells are made into the nutrient solution (DMEM or RMPI1640) containing 10% hyclone to hang
Liquid, 96 orifice plates are inoculated into every 10000-20000 cell in hole, per the μ l of pore volume 100, and attached cell shifts to an earlier date inoculation training in 12 hours
Support.
2. adding testing compound solution, (40 μM of primary dcreening operations of fixed concentration suppress in the concentration to growth of tumour cell
Compound near 50% sets 5 concentration into gradient secondary screening), per the μ l of hole final volume 200, every kind of processing is all provided with 3 multiple holes.
3. colour developing:After 37 degrees Celsius are cultivated 48 hours, add the μ l of MTT solution 20 per hole.Continue to be incubated 4 hours, terminate culture,
Careful inhale abandons in hole that the μ l of culture supernatant 100 are to avoid cell loss, the μ l of SDS 100 for adding 20% per hole, night incubation (temperature
37 DEG C), crystal is fully melted.
4. colorimetric:595nm wavelength is selected, enzyme-linked immunosorbent assay instrument (Bio-Rad 680) reads each hole absorbance value, record
As a result, using concentration as abscissa, cell survival rate is that ordinate draws cell growth curve, using two-point method (Reed and
Muench methods) calculate compound IC50Value.
Experimental result is shown in Table 1:
Half growth inhibitory concentration IC of the raw element A (spiratisanin A) of meadow sweet Ah Ti of table 1. to tumor cell line50
(μM)
Above-mentioned result of the test shows that meadow sweet Ah Ti is raw, and element A (spiratisanin A) has significant antitumor activity,
Clinical antitumor agents cis-platinum is particularly exceeded to breast cancer, the inhibitory activity of liver cancer.
Embodiment
Substantive content with reference to embodiment further to the present invention is illustrated, but present disclosure is not limited to
In this.
Embodiment 1:
The preparation method and structural characterization of the compounds of this invention:
1. preparation method:
6.5kg pink blossoms meadow sweet dries herb and extracted at room temperature 3 times with 95% ethanol after crushed, and 3 to 4 are extracted every time
My god, merge extract solution, be concentrated under reduced pressure, obtain 250g medicinal extract.Gained medicinal extract is separated through silica gel column chromatography again, with petroleum ether/acetone
Dicyandiamide solution carries out gradient elution, in petroleum ether/acetone (10:1) Duan get Yi components are eluted.The component is further through silica gel (chlorine
Imitative/methanol 60:1 elution), Sephadex LH-20 (chloroform/methanols 1:1 elution) and middle compacting for (methanol/water 85% is eluted)
Column chromatography for separation, obtains meadow sweet Ah Ti and gives birth to element A (spiratisanin A) sterling 10mg.
2. structural characterization:
White powder;Molecular formula C29H40O3;ESIMS(pos.):m/z 459[M+Na]+;HRESIMS:m/z 459.2881
[M+Na]+(459.2875calcd for C29H40O3Na);UV
(MeOH)λmax:217,222(sh),277nm;IR(KBr)νmax 3441,2954,2922,2868,2851,1708,1637,
1450,1310,1272,1203,1175,1045,979,768cm–1;Nmr spectrum data is shown in Table 2.
Nmr spectrum data (the CDCl of the raw element A (spiratisanin A) of meadow sweet Ah Ti of table 2.3It is middle to determine)
The chemical structural formula of the raw element A (spiratisanin A) of meadow sweet Ah Ti is:
Embodiment 2:
Tablet:Embodiment 1 gained compound 10mg, lactose 180mg, starch 55mg, magnesium stearate 5mg;
Preparation method:Compound, lactose, starch are mixed, is uniformly moistened with water, the mixture after moistening is sieved and done
Dry, re-sieving adds magnesium stearate, then by mixture tabletting, every weight 250mg, wherein compounds content 10mg.
Embodiment 3:
Capsule:Embodiment 1 gained compound 100mg, starch 100mg, Magnesium Stearate proper quantity;
Preparation method:Compound is mixed with auxiliary agent, sieves, is uniformly mixed in suitable container, by gained mixture
Load hard gelatin capsule.
Embodiment 4:
Ampulla:Embodiment 1 gained compound 2mg, sodium chloride 10mg;
Preparation method:Compound and sodium chloride are dissolved in appropriate water for injection, filtered, resulting solution is in sterile bar
It is fitted under part in ampoule bottle.
Claims (4)
1. following structural formula I:
2. the preparation method of the compound of formula I described in claim 1, this method comprises the following steps:
6.5kg pink blossoms meadow sweet dries herb and extracted at room temperature 3 times with 95% ethanol after crushed, extracts 3 to 4 days every time, closes
And extract solution, it is concentrated under reduced pressure, obtains 250g medicinal extract, gained medicinal extract is separated through silica gel column chromatography again, with petroleum ether/acetone solvent body
System carries out gradient elution, in petroleum ether/acetone 10:1 elution Duan get Yi components, the component is further through silica gel chloroform/methanol 60:
1 elution, Sephadex LH-20 chloroform/methanols 1:1 elution and the standby methanol/water 85% of middle compacting are eluted, and obtain meadow sweet Ah replacing
Raw element A sterling 10mg, i.e. compound of formula I described in claim 1.
3. for treating the pharmaceutical composition of tumour, wherein compound of formula I described in the claim 1 containing therapeutically effective amount and
Pharmaceutical acceptable carrier.
4. application of the compound of formula I in the medicine for treating and preventing tumour is prepared described in claim 1.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510700064.7A CN105541631B (en) | 2015-10-26 | 2015-10-26 | Raw element A (spiratisanin A) of meadow sweet Ah Ti and preparation method thereof and the application on medicine |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510700064.7A CN105541631B (en) | 2015-10-26 | 2015-10-26 | Raw element A (spiratisanin A) of meadow sweet Ah Ti and preparation method thereof and the application on medicine |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105541631A CN105541631A (en) | 2016-05-04 |
CN105541631B true CN105541631B (en) | 2017-09-05 |
Family
ID=55821250
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510700064.7A Active CN105541631B (en) | 2015-10-26 | 2015-10-26 | Raw element A (spiratisanin A) of meadow sweet Ah Ti and preparation method thereof and the application on medicine |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105541631B (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107840836A (en) * | 2016-09-18 | 2018-03-27 | 云南西力生物技术股份有限公司 | Icariine K and preparation method thereof and the application on medicine |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1254515B (en) * | 1992-03-06 | 1995-09-25 | Indena Spa | TASSANI OF ONCOLOGICAL INTEREST, THEIR METHOD OF PREPARATION AND USE |
CN1050359C (en) * | 1997-07-23 | 2000-03-15 | 中国科学院昆明植物研究所 | Diterpene salicylate alkaloid, preparation and use thereof |
KR100888002B1 (en) * | 2001-04-27 | 2009-03-09 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | Novel atisane compound and use thereof |
CN1393438B (en) * | 2001-06-21 | 2010-11-03 | 中国医学科学院药物研究所 | Taxane derivative and its preparing process and usage |
US20080206365A1 (en) * | 2007-02-28 | 2008-08-28 | Yoshihisa Tachibana | Diterpene compounds having an atisane framework, compositions thereof, and methods of production |
-
2015
- 2015-10-26 CN CN201510700064.7A patent/CN105541631B/en active Active
Also Published As
Publication number | Publication date |
---|---|
CN105541631A (en) | 2016-05-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101045046B (en) | Use of Brazil hemoatoxy type compound for preparing antineoplastic | |
CN107840836A (en) | Icariine K and preparation method thereof and the application on medicine | |
CN105985358B (en) | Liu Yazi total alkaloid extract and its preparation method and application | |
CN105541631B (en) | Raw element A (spiratisanin A) of meadow sweet Ah Ti and preparation method thereof and the application on medicine | |
CN101948453B (en) | Novel NEO-clerodane typed diterpene compound and application thereof | |
CN109453183B (en) | Tumor multidrug resistance reversal agent or anti-tumor medicine sensitizer of melissoside and application thereof | |
CN109867649B (en) | Biflavonoid compound and preparation method and application thereof | |
CN113480590B (en) | Wilforinupinone, its preparation method and application in medicine | |
CN103864765B (en) | Benzazepine analog derivative containing five-membered ring, Preparation Method And The Use | |
CN106749124B (en) | Neighbour's double tetrahydrofuran type Annonaceousacetogenicompounds compounds with anti-tumor activity and the preparation method and application thereof | |
CN102070573B (en) | Mono-tetrahydrofuran type sugar apple lactone compound with anti-tumor activity and application thereof | |
CN104447655A (en) | Novel sesquiterpene coumarins in ferula sinkiangensis K.M.Shen as well as preparation methods and medical applications of novel sesquiterpene coumarins | |
CN104257641B (en) | A kind of C36Polyacetylene compound and preparation thereof and application | |
CN102858359B (en) | Medicinal composition comprising alcohol-soluble and water-insoluble licorice extract, pharmaceutical preparation, pharmaceutical application, therapeutic method, and preparative method thereof | |
CN104610207B (en) | Gardenia sootepensis gardenin A, preparation method and medicinal application thereof | |
CN105541858B (en) | Xanthone class compounds and preparation method thereof, composition and purposes | |
CN101077873B (en) | Novel NEO-clerodane type diterpene compound and application thereof | |
CN109111462B (en) | Salvianolide, preparation method thereof and medicine containing same | |
CN113321631B (en) | Biandrographolide G, preparation method and application thereof in medicines | |
CN101569654A (en) | Supercritical extract of pigeon pea leaves and application of pigeon pea stilbene acid in the preparation of antitumor drug | |
CN105343888B (en) | Taccalonolide cyclodextrin inclusion compound and preparation method thereof and a kind of pharmaceutical composition | |
CN102838652B (en) | A kind of oleanolic acid derivate with anticarcinogenesis and its production and use | |
CN104529968A (en) | Anti-tumor diterpenoid compound, and pharmaceutical composition, preparation method and application thereof | |
CN102153529B (en) | Single-tetrahydrofuran-type annonaceous acetogenin compounds with antitumor activity and application thereof | |
CN101805355B (en) | Thienopyridone derivative, preparation method and uses thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |