CN105541858B - Xanthone class compounds and preparation method thereof, composition and purposes - Google Patents
Xanthone class compounds and preparation method thereof, composition and purposes Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
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Abstract
The present invention relates to native compound field, can extract the noval chemical compound with following structural formula obtained, or its pharmaceutically acceptable salt, hydrate or prodrug and preparation method thereof, pharmaceutical composition and purposes from Cortex Garciniae oliganthae more particularly to two kinds：Wherein R is selected from methyl or CH2CH2CH=C (CH3)2.The compound of the present invention can be used for the medicine product for preparing the kinds of tumors such as preventing and treating prostate cancer, liver cancer, lung cancer and colon cancer.
Description
Technical field
The present invention relates to native compound field, more particularly to a kind of xanthone classes compound and preparation method thereof,
Pharmaceutical composition and purposes.
Background technology
Malignant tumour is current threat human health and the principal disease of life.In most of developed countries, tumour is only
Inferior to the second largest cause of death of cardiovascular disease.Tumour is also to seriously endanger the major disease of the health of our people, and China swells
Knurl research is also paid attention to by government, and control tumour turns into one of China's health strategy emphasis.
The treatment method of tumour includes surgical operation and chemicotherapy.The outstanding problem of the antineoplastic of Present clinical application
It is efficient low, poor selectivity (toxicity is big) and to the insensitive of resistant tumors.In addition, recurrence and transfer and oncotherapy
Difficult point.Therefore, studying the antineoplastic that selectivity is good, curative effect is high, target spot is clear and definite and has no side effect to non-target organ is
The great research topic of pharmacy worker.
Cortex Garciniae oliganthae (scientific name：Garcinia oligantha Merr.) belong to shrub.It is distributed in Vietnam and China
The ground such as Guangdong, Hainan, 200 meters to 1 of height above sea level is grown on, 200 meters of area, is often born in the jungle of mountain region.
The content of the invention
The purpose of the present invention aims to provide two kinds can extract the antitumoral compounds obtained and its system from Cortex Garciniae oliganthae
Preparation Method and purposes.
Specifically, the first aspect of the present invention there is provided a kind of compound A, or its pharmaceutically acceptable salt, water
Compound or prodrug, it is characterised in that the compound A can extract from Cortex Garciniae oliganthae to be obtained and have following structural (I)：
Wherein R is selected from methyl or-CH2CH2CH=C (CH3)2。
The second aspect of the present invention there is provided a kind of compound B, or its pharmaceutically acceptable salt, hydrate or preceding
Medicine, it is characterised in that the compound B can extract from Cortex Garciniae oliganthae to be obtained and have following structural (II)：
The third aspect of the present invention there is provided a kind of compound A preparation method, when R is methyl, methods described bag
Include following steps：
A) it is Cortex Garciniae oliganthae leaf is colourless to percolate with petroleum ether seepage pressure effects, percolate is evaporated under reduced pressure, obtains extract；
B) by the extract ethanol obtained by step a) and water according to 1:Add after the mixed solution dissolving that 1 volume ratio is formed
On MCI posts, washed successively with 30% ethanol water, 60% ethanol water, 90% ethanol water, 95% ethanol water
It is de-, collect eluent respectively, every part of eluent be evaporated under reduced pressure after through TLC tlc analysis, it is main by what is shown on TLC lamellaes
Point identical eluate merges, and five components are obtained by eluting order；
C) by second component obtained in step b) by ODS middle compacting for chromatogram, with methanol and water according to 30:70
To 100:The mixed solution that 0 volume ratio is formed gradient elution successively, every part of eluent be evaporated under reduced pressure after through TLC tlc analysis,
The main point identical eluate shown on TLC lamellaes is merged, 13 components are obtained by eluting order；
D) the 11st component methanol gel post obtained in step c) is purified, obtains target compound；
When R is-CH2CH2CH=C (CH3)2When, methods described comprises the following steps：
A) it is Cortex Garciniae oliganthae leaf is colourless to percolate with petroleum ether seepage pressure effects, obtain diacolation slag；
B) the diacolation slag obtained by step a) is colourless to percolate with 90% ethanol water seepage pressure effects, reduction vaporization oozes
Filter liquid, obtain extract；
C) extract obtained by step b) is dissolved with water, be extracted with ethyl acetate, extract is evaporated under reduced pressure, must extract
Thing；
D) by the extract chloroform obtained by step c) and methanol according to 1:The mixed solution dissolving that 1 volume ratio is formed is simultaneously
Mix thoroughly with proper silica gel, be added in after removing solvent on the silicagel column of 20 times of amounts, with dichloromethane and methanol according to 1:0 to 1:1
The mixed solution gradient elution successively that volume ratio is formed, collects eluent respectively, every part of eluent be evaporated under reduced pressure after through TLC thin layers
Chromatography, the main point identical eluate shown on TLC lamellaes is merged, five components are obtained by eluting order；
E) it is water-soluble with 30% ethanol water, 60% ethanol by first component obtained in step d) by MCI posts
Liquid, 90% ethanol water, 95% ethanol water elute successively, eluent are collected respectively, after every part of eluent is evaporated under reduced pressure
Through TLC tlc analysis, the main point identical eluate shown on TLC lamellaes is merged, 11 are obtained by eluting order
Individual component；
F) by the obtained in step e) the tenth component by gel column, with chloroform and methanol according to 1:1 volume ratio shape
Into mixed solution elution, collect eluent respectively, every part of eluent be evaporated under reduced pressure after through TLC tlc analysis, by TLC lamellaes
The main point identical eluate of upper display merges, and four components are obtained by eluting order；
G) by second component obtained in step f) by suppressing standby chromatogram in ODS, with methanol and water according to 30:70 to
100:The mixed solution that 0 volume ratio is formed gradient elution successively, collects eluent, every part of eluent passes through after being evaporated under reduced pressure respectively
TLC tlc analysis, the main point identical eluate shown on TLC lamellaes is merged, ten groups are obtained by eluting order
Point；
H) the 6th component methanol gel post in step g) is purified, obtains target compound.
The fourth aspect of the present invention there is provided a kind of compound B preparation method, and methods described comprises the following steps：
A) it is Cortex Garciniae oliganthae leaf is substantially colorless to percolate with petroleum ether seepage pressure effects, percolate is evaporated under reduced pressure, must carry
Take thing；
B) by the extract ethanol obtained by step a) and water according to 1:Add after the mixed solution dissolving that 1 volume ratio is formed
On MCI posts, washed successively with 30% ethanol water, 60% ethanol water, 90% ethanol water, 95% ethanol water
It is de-, collect eluent respectively, every part of eluent be evaporated under reduced pressure after through TLC tlc analysis, it is main by what is shown on TLC lamellaes
Point identical eluate merges, and five components are obtained by eluting order；
C) by the 3rd component of gained in step b) by ODS middle compacting for chromatogram, with methanol and water according to 30:70
To 100:The mixed solution that 0 volume ratio is formed gradient elution successively, collects eluent, after every part of eluent is evaporated under reduced pressure respectively
Through TLC tlc analysis, the main point identical eluate shown on TLC lamellaes is merged, ten are obtained by eluting order
Component；
D) the obtained in step c) the 5th component methanol gel post is purified, obtains target compound.
The fifth aspect of the present invention there is provided a kind of pharmaceutical composition of anti-curing oncoma, and the composition has comprising treatment
The above-mentioned compound A or compound B of effect amount, or its pharmaceutically acceptable salt, hydrate or prodrug.
In a preference, one or more of the tumour in prostate cancer, liver cancer, lung cancer and colon cancer.
The sixth aspect of the present invention there is provided above-claimed cpd A or compound B, or its pharmaceutically acceptable salt, water
The application of compound or prodrug in tumor cell Cycle Arrest derivant is prepared.
In a preference, the tumour cell is non-selected from Human Prostate Cancer Cells PC-3, human liver cancer cell HepG2, people
One or more in small cell lung cancer cell A549 and human colon cancer cell HT-29.
The eighth aspect of the present invention there is provided above-claimed cpd A or compound B, or its pharmaceutically acceptable salt, water
The application of compound or prodrug in the medicine or health products for preparing prevention or treatment tumour.
In a preference, one or more of the tumour in prostate cancer, liver cancer, lung cancer and colon cancer.
The details of various aspects of the present invention will be able to detailed description in subsequent chapters and sections.By hereafter and claim
Description, the features of the present invention, purpose and advantage will become apparent from.
Brief description of the drawings：
Fig. 1 Oliganthin I, Oliganthin H, Oliganthone B suppress the IC50 values of growth of tumour cell.
Embodiment
The appearance of the present invention is had been surprisingly found that based on such a：The two class Xanthone classes extracted from Cortex Garciniae oliganthae
Compound can significantly inhibit the growth of kinds of tumor cells and the cell cycle of inducible tumour cell blocks.Therefore,
Compound A and B, refer specifically to compound Oliganthin I, Oliganthin H, Oliganthone B and be expected to be developed into one
The medicine of tumour can be prevented or be treated to kind.
And then present invention firstly provides a kind of compound A with following structural (I) and with following structural
(II) compound B, it is specific as follows：
Wherein R is selected from methyl or-CH2CH2CH=C (CH3)2。
When R is methyl, compound is Oliganthin I, molecular formula：C28H30O7, molecular weight：478, structural formula (I -1)
It is as follows：
Oliganthin I,
When R is-CH2CH2CH=C (CH3)2When, compound is Oliganthin H, molecular formula：C33H38O7, molecular weight：
546, structural formula (I -2) is as follows：
Oliganthin H,
Compound B is named as Oliganthone B, molecular formula：C29H32O7, molecular weight：492, structural formula (II) is as follows：
B(Oliganthone B)
Present invention also offers corresponding all pharmaceutically acceptable salt, hydrate or the prodrugs of above-claimed cpd.
These salt can be by part (for example, amido) positively charged in compound with having the negatively charged (for example, three of opposite-sign
Fluorine acetic acid) formed；Or by part (for example, carboxyl) negatively charged in compound and positive charge (for example, sodium, potassium, calcium, magnesium)
Formed.Compound can contain a nonaromatic double bond, have one or more asymmetric centers.So these compounds
Racemic mixture, single enantiomter, single diastereoisomer, diastereoisomer mixing can be used as
Thing, cis or trans isomers are present.All these isomers are all expected.It is described " structural formula be respectively (I -1),
The prodrug of the compound of (I -2), (II) " generally refers to a kind of material respectively, can be in subject's body after being applied with appropriate method
It is respectively (I -1), (I -2), at least one compound of (II) to be inside metabolized or chemically reacted and be transformed into structural formula respectively
Or its salt.
The structural formula of the present invention be respectively (I -1), (I -2), (II) compound can be by the conventional method of this area such as
Alcohol extracting, chromatography etc. are extracted from the plants such as Cortex Garciniae oliganthae and obtained, and can also be bought by commercial sources or using marketable material,
Synthesized and obtained by compound synthesis method traditional in the prior art.One of ordinary skill in the art is according to existing known skill
Art can synthesize the compound of the present invention.The compound of synthesis can further by column chromatography, high performance liquid chromatography or
The modes such as crystallization are further purified.
Synthesize chemical improvement, protection functional group methodology (protection or deprotection) is helpful to synthesis application compound
, and be known technology of the prior art, such as R.Larock, Comprehensive Organic
Transformations,VCH Publishers(1989)；T.W.Greene and P.G.M.Wuts,Protective
Groups in Organic Synthesis,3rdEd.,John Wiley and Sons(1999)；L.Fieser and
M.Fieser,Fieser and Fieser’s Reagents for Organic Synthesis,John Wiley and
Sons(1994)；and L.Paquette,ed.,Encyclopedia of Reagents for Organic Synthesis,
There is disclosure in John Wiley and Sons (1995).
The structural formula of the present invention is respectively (I -1), (I -2), the compound of (II) or its pharmaceutically acceptable salt, hydration
Thing or prodrug can effectively suppress the propagation of a variety of human tumor cells, so the compound of the present invention or its is pharmaceutically acceptable
Salt, hydrate or prodrug can be used for prepare anti-tumor drug.
Present invention also offers a kind of composition, said composition includes compound of the invention or its is pharmaceutically acceptable
Salt, hydrate or prodrug, with pharmaceutically acceptable carrier, said composition can be used for treating tumour.
Present invention also offers a kind of pharmaceutical preparation, the pharmaceutical preparation include one or more of present invention compounds or its
Pharmaceutically acceptable salt, hydrate or prodrug.The pharmaceutical preparation can be used for treating tumour.
The structural formula of the present invention is respectively (I -1), (I -2), the compound of (II) or its pharmaceutically acceptable salt, hydration
The content of thing or prodrug in composition or pharmaceutical preparation such as 0.0001-50wt%；Preferable 0.001-30wt%；More
0.01-20wt%.
The dosage of the composition of the invention of therapeutically effective amount is between 0.001-500mg/kg body weight/days, Ren Hejie
Dosage within above range is all the effective dose of the present invention.Preferably, the dosage of composition of the invention is between 0.005-
Between 300mg/kg body weight/days；It is furthermore preferred that the present invention composition dosage between 0.01-100mg/kg body weight/days it
Between.Described " therapeutically effective amount " can be used for single drug or the drug combination treatment of relevant disease.One of skill in the art
It is understood that the dosage when being actually administered can be higher or lower than above-mentioned dosage range.For a certain object (such as mammal-
People) " therapeutically effective amount " and specific therapeutic scheme can be influenceed by factors, including the medicine of compound used therefor or its prodrug
Imitate activity, the age of administration object, body weight, ordinary circumstance, sex, diet, administration time, disease susceptibility, disease process with
And judgement for the treatment of physician etc.." treatment " refer to giving body (symptom containing tumour, with tumour or with
The omen of tumour) structural formula of the present invention is respectively (I -1), (I -2), the compound of (II), treating, mitigating, slowing down, changing
Become, cure, influenceing, improving the omen of its tumour, the symptom of tumour or tumour.
The structural formula of the present invention is respectively (I -1), (I -2), the compound of (II) or its pharmaceutically acceptable salt, hydration
Thing or prodrug or its composition or its pharmaceutical preparation can be by oral, intravenous, intramuscular, in subcutaneous, nasal cavity, in rectum etc.
Approach is administered.Solid carrier is such as：Starch, lactose, phosphoric acid glycol, microcrystalline cellulose, brown sugar and white bole, and liquid carrier is such as：
Sterilized water, polyethylene glycol, nonionic surface active agent and edible oil (such as corn oil, peanut oil and sesame oil), as long as being adapted to
The characteristic of active component and required specific administration mode.Also can be favourable preparing adjuvant usually used in pharmaceutical composition
Ground is included, e.g., flavor enhancement, pigment, preservative and antioxidant such as vitamin E, vitamin C, BHT and BHA.
The present invention structural formula be respectively (I -1), (I -2), (II) compound also can parenteral or intraperitoneal administration.
Can it is appropriate be mixed with the water of surfactant (such as hydroxypropyl cellulose) prepare these reactive compounds (as free alkali or
Pharmaceutically acceptable salt) solution or suspension.It can also be prepared in glycerine, polyethylene glycol and its mixture in oil point
Dispersion liquid.Under conventional storage and use condition, containing preservative to prevent the growth of microorganism in these preparations.
Include suitable for the medicament forms of injection：Aseptic aqueous solution or dispersion liquid and aseptic powder (are used for extemporaneous preparation of sterile
Parenteral solution or dispersion liquid).In all situations, these forms must be sterile and must be that fluid is discharged with being easy to syringe
Fluid.It must be stable under conditions of manufacture and storage, and must be able to prevent pollution and the shadow of microorganism such as bacterium and fungi
Ring.Carrier can be solvent or decentralized medium, wherein containing such as water, alcohol, their appropriate mixture and vegetable oil.
The experimental method of unreceipted actual conditions in the following example, generally according to normal condition or according to institute of manufacturer
It is recommended that condition.Unless otherwise indicated, otherwise all percentage, ratio, ratio or number be by weight.
Unless otherwise defined, anticipated known to all specialties used in text and scientific words and one skilled in the art
Justice is identical.In addition, any method similar or impartial to described content and material all can be applied in the inventive method.This
Preferable implementation described in text only presents a demonstration with material to be used.
The features described above that the present invention mentions, or the feature that embodiment is mentioned can be in any combination.Patent specification is taken off
All features shown can be used in combination with any combinations thing form, each feature disclosed in specification, can provide phase with any
The alternative characteristics substitution of same, impartial or similar purpose.Therefore except there is special instruction, disclosed feature is only impartial or similar
The general example of feature.
Embodiment 1 is extracted from Cortex Garciniae oliganthae leaf and identifies Oliganthin I, Oliganthone B and
Oliganthin H
1.1 experiment material
Cortex Garciniae oliganthae picks up from Hainan Province in September, 2013, and plant is identified through Agricultural University Of South China doctor Zhang Rongjing.
Plant sample is stored in Shanghai Univ. of Traditional Chinese Medicine's Innovative TCMs laboratory.
1.2 test method
At room temperature, take Cortex Garciniae oliganthae leaf powder (2.4 kilograms), with petroleum ether seepage pressure effects to percolate substantially without
Color, percolate is evaporated under reduced pressure, obtains 30 grams of dirty-green extract (A)；The dregs of a decoction continue to be extracted to percolate with 90% ethanol percolation
It is substantially colorless, percolate is evaporated under reduced pressure, obtains 460 grams of dirty-green extract (B).
It is added in after extract A is dissolved with alcohol-water mixed solution on MCI posts, with 30% ethanol water, 60% ethanol
The aqueous solution, 90% ethanol water, 95% ethanol water elute successively, are collected in elution process by 500 milliliters every bottle, every bottle
Through TLC tlc analysis after eluent reduction vaporization, the main point identical that will be shown by analysis result on TLC lamellaes elutes
Thing merges, and obtains 5 components, wherein first component being eluted first is component 1 (A1), be arranged in order to obtain component 1 to
Component 5 (A1-A5).
Component 2 (A2) (4.0 grams) by ODS middle compacting for chromatogram, with methanol/water gradient system (30:70 to 100:0,
Volume/volume) elute successively, eluent is collected by 100 milliliters every bottle, will through tlc analysis after every bottle of eluent reduction vaporization
The main point identical eluate shown on TLC lamellaes merges, and obtains 13 components, is eluted first by eluting order
Component is component 1 (A2.1), is arranged in order to obtain component 1 to component 13 (A2.1-A2.13).Wherein component 11 (A2.11) (0.7
Gram) with methanol gel post purify obtain Oliganthin I (200 milligrams).
Extract A component 3 (A3) (3.8 grams) isolated on MCI posts by ODS in suppress standby chromatogram, with methanol/
Water gradient system (30:70 to 100:0, volume/volume) elute successively, collected in separation process by 100 milliliters every bottle, every bottle is washed
Through tlc analysis after de- liquid reduction vaporization, the main point identical eluate that will be shown on TLC lamellaes merges, and obtains 10
Component, the component being eluted first by eluting order is component 1 (A3.1), is arranged in order to obtain component 1 to the (A3.1- of component 10
A3.10).Wherein component 5 (A3.5) (40 milligrams) methanol gel post, which is purified, obtains Oliganthone B (2.6 milligrams).
Extract B is dissolved with water, is extracted with ethyl acetate, extract is evaporated under reduced pressure, obtains dirty-green extract 286
Gram.The extract is dissolved with chloroform-methanol mixed solution and mixed thoroughly with proper silica gel, and 20 times of silica gel measured are added in after removing solvent
On post, with methylene chloride-methanol (1:0 to 1:1, volume/volume) gradient elution successively, 500 milliliters every bottle are pressed in elution process
Collect, after every bottle of eluent is evaporated under reduced pressure, through TLC tlc analysis, the main point identical shown on TLC lamellaes is eluted
Thing merges, and obtains five components, and the component being eluted first by eluting order is component 1 (B1), be arranged in order to obtain component 1 to
Component 5 (B1-B5).Wherein component 1 (B1) (24 grams) is water-soluble with 30% ethanol water, 60% ethanol successively by MCI posts
Liquid, 90% ethanol water, 95% ethanol water elute, and are collected in elution process by 250 milliliters every bottle, and every bottle of eluent subtracts
Through TLC tlc analysis after pressure evaporation, the main point identical eluate shown on TLC lamellaes is merged, obtains 11
Component, the component being eluted first by eluting order is component 1 (B1.1), is arranged in order to obtain component 1 to the (B1.1- of component 11
B1.11).Wherein component 10 (B1.10) (4.8 grams) is by gel column, with chloroform-methanol (1:1, volume/volume) elution, elution
Process is collected by 20 milliliters every bottle, through TLC tlc analysis after every bottle of eluent reduction vaporization, the master that will be shown on TLC lamellaes
The point identical eluate wanted merges, and obtains four components, the component being eluted first by eluting order is component 1
(B1.10.1) it is logical to component 4 (B1.10.1-B1.10.4), wherein (4 grams) of component 2 (B1.10.2), to be arranged in order to obtain component 1
Cross in ODS and suppress standby chromatogram, with methanol/water gradient system (30:70 to 100:0, volume/volume) elute successively, elution process
In collected by 100 milliliters every bottle, every bottle of eluent be evaporated under reduced pressure after through TLC tlc analysis, it is main by what is shown on TLC lamellaes
Point identical eluate merge, obtain ten components, the component being eluted first by eluting order is component 1
(B1.10.2.1), it is arranged in order to obtain component 1 to component 10 (B1.10.2.1-B1.10.2.10), wherein component 6
(B1.10.2.6) (540 milligrams) are purified to obtain Oliganthin H (500mg) with methanol gel post.
In this experiment, MCI posts from CHP20P MCI gel (75-150 μm, Mitsubishi Chemical
Coparation,Japan)；Silica gel column chromatography selects Qingdao Marine Chemical Co., Ltd.'s column chromatography silica gel (200-300 mesh)；TLC
Tlc analysis selects Yantai Jiang You silica gel development corporation, Ltd. HSGF254 tlc silica gel plates；Standby chromatographic column is suppressed in ODS to select
With reversed-phase C18silica gel (50 μm, YMC, Kyoto, Japan)；Gel column selects Sephadex LH-20
(GE Healthcare Bio-Sciences AB, Sweden) is filler.
Oliganthin I are yellow, an amorphous powder, determine that molecular formula is C by high resolution mass spectrum28H30O7, it is
One has no the noval chemical compound of report.Its NMR data is as follows：
Oliganthin H are yellow, an amorphous powder, determine that molecular formula is C by high resolution mass spectrum33H38O7, it is
One has no the noval chemical compound of report.Determine that Oliganthin H absolute configuration is 8R configurations by single crystal X-ray diffraction.Its
NMR data is as follows：
Oliganthone B are yellow, an amorphous powder, determine that molecular formula is C by high resolution mass spectrum28H30O7,
For a noval chemical compound for having no report, by the calculating of circular dichroism spectra, it is 5R, 7R, 10aS, 22R to determine its absolute configuration.Its
NMR data is as follows：
1.3 experimental result
Isolated compound Oliganthin I, Oliganthin H, Oliganthone B from Cortex Garciniae oliganthae,
Through nuclear-magnetism and Mass Spectrometer Method, chemical constitution is respectively as shown in (I -1), (I -2), (II)：
The Oliganthin I of embodiment 2, Oliganthin H, Oliganthone B suppress human tumor cells propagation
2.1 experiment material
Human Prostate Cancer Cells PC-3, human liver cancer cell HepG2 are thin purchased from ATCC companies of the U.S., Non-small cell lung carcinoma
Born of the same parents A549, people normal cell lines of human liver Hl7702, Hong Kong Chinese University professor Lin Ge grant, human colon cancer cell HT-29, Tsing-Hua University
Professor Xu Naihan grants.
RPMI1640 is purchased from hyclone companies of the U.S., and DMEM is purchased from Gibco companies of the U.S., and hyclone is purchased from German PAN
Company, penicillin and streptomysin are purchased from Hangzhou Ji Nuo companies, and Taxol is purchased from German sigma companies.
2.2 experimental method
Non-small cell lung carcinoma cell A549, human liver cancer cell HepG2, with containing 10% hyclone, 100U/ml penicillin
Liquid-based is trained with the DMEM of 100 μ g/ml streptomysins, Human Prostate Cancer Cells PC-3, human colon cancer cell HT-29 and people liver are normally thin
The born of the same parents Hl7702 RPMI1640 training liquid-baseds for containing 10% hyclone, 100U/ml penicillin and 100 μ g/ml streptomysins, in 37
DEG C, 5%CO2And cultivated in the incubator of saturated humidity, passed on 0.25% Trypsin Induced, growth period cell of taking the logarithm is used
In experiment.
Human Prostate Cancer Cells PC-3, Non-small cell lung carcinoma cell A549, human liver cancer cell HepG2, human colon carcinoma are thin
Born of the same parents HT-29 and people's normal cell lines of human liver Hl7702 (4000 cells/wells) are inoculated in 96 orifice plates.Being separately added into concentration gradient is
1.25 μM, 2.5 μM, 5 μM, 10 μM of Oliganthin I, OliganthinH, Oliganthone B in 96 orifice plates,
Paclitaxel after cultivating 72h, 10ul MTT is added per hole, lucifuge is incubated 4h and dyed as positive drug control group.Then
Culture medium is suctioned out, 150 μ l DMSO is added, absorbance is detected under 570nm using ELIASA, various concentrations are calculated with excel
Growth inhibition ratio, growth inhibition ratio=(average value of average value-treatment group of control groups)/control average value ×
100.When the growth inhibition ratio of cell reaches 50%, Oliganthin I, Oliganthin H, Oliganthone B it is dense
Degree is IC50 values.Experimental data is represented with mean+/-standard error.
2.3 experimental result
As a result as shown in table 1 and Fig. 1, Oliganthin I, Oliganthin H, Oliganthone B are respectively acting on
After PC-3, A549, HepG2, HT-29 and Hl7702 cell 72 hours, it can substantially suppress the activity of cell propagation.Result above can
To prove that Oliganthin I, Oliganthin H, Oliganthone B can suppress the increasing of tumour cell concentration dependent
Grow ability.
The IC50 that Oliganthin I, Oliganthin H, Oliganthone B act on a variety of human tumour 72h is as follows
Shown in table.
The Oliganthin I of table 1, Oliganthin H, Oliganthone B suppress the IC50 values of growth of tumour cell
This experiment proves：Oliganthin I, Oliganthin H, Oliganthone B, which have, suppresses tumour cell increasing
The effect grown, show that Oliganthin I, Oliganthin H, Oliganthone B have potential antitumor action, can be with
Medicine or health products as treatment tumour.
Many aspects involved in the present invention have been explained as above.However, it should be understood that without departing from spirit of the invention
Under the premise of, those skilled in the art can carry out equivalent change and modification to it, and the change and modification equally fall into the application
The coverage of appended claims.
Claims (10)
1. a kind of compound A, or its pharmaceutically acceptable salt, it is characterised in that the compound A can be from Cortex Garciniae oliganthae
Extraction obtains and has following structural (I)：
Wherein R is selected from methyl or-CH2CH2CH=C (CH3)2。
2. a kind of compound B, or its pharmaceutically acceptable salt, it is characterised in that the compound B can be from Cortex Garciniae oliganthae
Extraction obtains and has following structural (II)：
A kind of 3. compound A as claimed in claim 1 preparation method, it is characterised in that when R is methyl, methods described
Comprise the following steps：
A) it is Cortex Garciniae oliganthae leaf is colourless to percolate with petroleum ether seepage pressure effects, percolate is evaporated under reduced pressure, obtains extract；
B) by the extract ethanol obtained by step a) and water according to 1:It is added in after the mixed solution dissolving that 1 volume ratio is formed
On MCI posts, washed successively with 30% ethanol water, 60% ethanol water, 90% ethanol water, 95% ethanol water
It is de-, collect eluent respectively, every part of eluent be evaporated under reduced pressure after through TLC tlc analysis, it is main by what is shown on TLC lamellaes
Point identical eluate merges, and five components are obtained by eluting order；
C) by second component obtained in step b) by ODS middle compacting for chromatogram, with methanol and water according to 30:70 to
100:The mixed solution that 0 volume ratio is formed gradient elution successively, every part of eluent be evaporated under reduced pressure after through TLC tlc analysis, will
The main point identical eluate shown on TLC lamellaes merges, and 13 components are obtained by eluting order；
D) the 11st component methanol gel post obtained in step c) is purified, obtains target compound；
When R is-CH2CH2CH=C (CH3)2When, methods described comprises the following steps：
A) it is Cortex Garciniae oliganthae leaf is colourless to percolate with petroleum ether seepage pressure effects, obtain diacolation slag；
B) it is the diacolation slag obtained by step a) is colourless to percolate with 90% ethanol water seepage pressure effects, diacolation is evaporated under reduced pressure
Liquid, obtain extract；
C) extract obtained by step b) is dissolved with water, be extracted with ethyl acetate, extract is evaporated under reduced pressure, obtains extract；
D) by the extract chloroform obtained by step c) and methanol according to 1:The mixed solution that 1 volume ratio is formed dissolves and with fitting
Amount silica gel is mixed thoroughly, is added in after removing solvent on the silicagel column of 20 times of amounts, with dichloromethane and methanol according to 1:0 to 1:1 volume
Than the mixed solution gradient elution successively of formation, collect eluent respectively, every part of eluent be evaporated under reduced pressure after through TLC thin layers
Analysis, the main point identical eluate shown on TLC lamellaes is merged, five components are obtained by eluting order；
E) by first component obtained in step d) by MCI posts, with 30% ethanol water, 60% ethanol water,
90% ethanol water, 95% ethanol water elute successively, collect eluent respectively, and every part of eluent passes through after being evaporated under reduced pressure
TLC tlc analysis, the main point identical eluate shown on TLC lamellaes is merged, 11 are obtained by eluting order
Component；
F) by the obtained in step e) the tenth component by gel column, with chloroform and methanol according to 1:What 1 volume ratio was formed
Mixed solution elutes, and collects eluent respectively, every part of eluent be evaporated under reduced pressure after through TLC tlc analysis, will show on TLC lamellaes
The main point identical eluate shown merges, and four components are obtained by eluting order；
G) by second component obtained in step f) by suppressing standby chromatogram in ODS, with methanol and water according to 30:70 to 100:
The mixed solution that 0 volume ratio is formed gradient elution successively, collects eluent respectively, every part of eluent be evaporated under reduced pressure after through TLC
Tlc analysis, the main point identical eluate shown on TLC lamellaes is merged, ten components are obtained by eluting order；
H) the 6th component methanol gel post in step g) is purified, obtains target compound.
4. a kind of compound B as claimed in claim 2 preparation method, it is characterised in that methods described comprises the following steps：
A) it is Cortex Garciniae oliganthae leaf is substantially colorless to percolate with petroleum ether seepage pressure effects, percolate is evaporated under reduced pressure, obtains extract；
B) by the extract ethanol obtained by step a) and water according to 1:It is added in after the mixed solution dissolving that 1 volume ratio is formed
On MCI posts, washed successively with 30% ethanol water, 60% ethanol water, 90% ethanol water, 95% ethanol water
It is de-, collect eluent respectively, every part of eluent be evaporated under reduced pressure after through TLC tlc analysis, it is main by what is shown on TLC lamellaes
Point identical eluate merges, and five components are obtained by eluting order；
C) by the 3rd component of gained in step b) by ODS middle compacting for chromatogram, with methanol and water according to 30:70 to
100:The mixed solution that 0 volume ratio is formed gradient elution successively, collects eluent, every part of eluent passes through after being evaporated under reduced pressure respectively
TLC tlc analysis, the main point identical eluate shown on TLC lamellaes is merged, ten groups are obtained by eluting order
Point；
D) the obtained in step c) the 5th component methanol gel post is purified, obtains target compound.
A kind of 5. pharmaceutical composition of anti-curing oncoma, it is characterised in that the composition include therapeutically effective amount as right will
Ask the compound described in 1 or 2, or its pharmaceutically acceptable salt.
6. pharmaceutical composition as claimed in claim 5, it is characterised in that the tumour be selected from prostate cancer, liver cancer, lung cancer and
One or more in colon cancer.
7. compound as claimed in claim 1 or 2 or its pharmaceutically acceptable salt are preparing the resistance of tumor cell cycle
Application in stagnant derivant.
8. application as claimed in claim 7, the tumour cell are selected from Human Prostate Cancer Cells PC-3, human liver cancer cell
One or more in HepG2, Non-small cell lung carcinoma cell A549 and human colon cancer cell HT-29.
9. compound as claimed in claim 1 or 2 or its pharmaceutically acceptable salt are preparing the medicine of prevention or treatment tumour
Application in thing or health products.
10. application as claimed in claim 9, one kind in prostate cancer, liver cancer, lung cancer and colon cancer of the tumour or
It is a variety of.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP2108645A1 (en) * | 2008-04-07 | 2009-10-14 | INSERM (Institut National de la Santé et de la Recherche Medicale) | Use of xanthone derivatives as a medicament for cancer |
| CN102503951A (en) * | 2011-11-07 | 2012-06-20 | 中国药科大学 | Garcinia derivative and preparation method and medicinal application thereof |
| CN102796113A (en) * | 2012-09-03 | 2012-11-28 | 云南民族大学 | Xanthone compound, and preparation method and application thereof |
| US20140194498A1 (en) * | 2013-01-10 | 2014-07-10 | Hong Kong Baptist University | Polyisoprenylated tetracyclic xanthone with anticancer activity |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2108645A1 (en) * | 2008-04-07 | 2009-10-14 | INSERM (Institut National de la Santé et de la Recherche Medicale) | Use of xanthone derivatives as a medicament for cancer |
| CN102503951A (en) * | 2011-11-07 | 2012-06-20 | 中国药科大学 | Garcinia derivative and preparation method and medicinal application thereof |
| CN102796113A (en) * | 2012-09-03 | 2012-11-28 | 云南民族大学 | Xanthone compound, and preparation method and application thereof |
| US20140194498A1 (en) * | 2013-01-10 | 2014-07-10 | Hong Kong Baptist University | Polyisoprenylated tetracyclic xanthone with anticancer activity |
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