CN105541858A - Xanthone compositions, and preparation method, compositions and application thereof - Google Patents
Xanthone compositions, and preparation method, compositions and application thereof Download PDFInfo
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- C07—ORGANIC CHEMISTRY
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- 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
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Abstract
The invention relates to the field of natural compounds, especially to two novel compounds extracted from the bark of Garcinia oligantha and having a structural formula as described in the specification, or a pharmaceutically acceptable salt, hydrate or prodrug thereof, and a preparation method, a pharmaceutical composition and application thereof. In the formula, R is a methyl group or -CH2CH2CH=C(CH3)2. The compound can be used for preparation of drugs used for preventing and treating a plurality of tumors like prostatic cancers, liver cancers, lung cancers and colorectal cancers.
Description
Technical field
The present invention relates to natural compounds field, particularly relate to a kind of xanthone compounds and preparation method thereof, pharmaceutical composition and purposes.
Background technology
Malignant tumour is the principal disease of current threat human health and life.In most of developed country, tumour is the second largest cause of death being only second to cardiovascular diseases.Tumour is also the major disease of serious harm our people health, and the tumor research of China is also subject to the attention of government, and controlling tumour has become one of China's health strategy emphasis.
The methods for the treatment of of tumour comprises surgical operation and chemicotherapy.The outstanding problem of antitumor drug of Present clinical application is efficient low, poor selectivity (toxicity is large) and insensitive to resistant tumors.In addition, recurrence and transfer are also the difficult points of oncotherapy.Therefore, study that selectivity is good, curative effect is high, target spot is clear and definite and be the great research topic of pharmacy worker to the antitumor drug that non-target organ has no side effect.
Cortex Garciniae oliganthae (formal name used at school: GarciniaoliganthaMerr.) belongs to shrub.Be distributed in Vietnam and the ground such as Chinese Guangdong, Hainan, be grown on height above sea level 200 meters to the area of 1,200 meters, be often born in the jungle of mountain region.
Summary of the invention
Object of the present invention aims to provide two kinds can extract antineoplastic compound obtained and its production and use from Cortex Garciniae oliganthae.
Specifically, a first aspect of the present invention there is provided a kind of compd A, or its pharmacy acceptable salt, hydrate or prodrug, it is characterized in that, described compd A can extract and obtains and have having structure formula I from Cortex Garciniae oliganthae:
Wherein R is selected from methyl or-CH
2cH
2cH=C (CH
3)
2.
A second aspect of the present invention there is provided a kind of compd B, or its pharmacy acceptable salt, hydrate or prodrug, it is characterized in that, described compd B can extract and obtains and have having structure formula II from Cortex Garciniae oliganthae:
A third aspect of the present invention there is provided a kind of preparation method of compd A, and when R is methyl, described method comprises the steps:
A) by colourless to percolate for Cortex Garciniae oliganthae leaf sherwood oil seepage pressure effects, reduction vaporization percolate, obtains extract;
B) by step, a) the extract ethanol of gained and water are added on MCI post after dissolving according to the mixing solutions that the volume ratio of 1:1 is formed, with 30% aqueous ethanolic solution, 60% aqueous ethanolic solution, 90% aqueous ethanolic solution, 95% aqueous ethanolic solution wash-out successively, collect elutriant respectively, through TLC tlc analysis after every part of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtains five components by elution order;
C) by step b) in second component obtaining by pressing preparative chromatography in ODS, with the mixing solutions gradient elution successively that methyl alcohol and water are formed according to the volume ratio of 30:70 to 100:0, through TLC tlc analysis after every part of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtains 13 components by elution order;
D) by step c) in the 11 component methanol gel column purification obtaining, obtain target compound;
When R is-CH
2cH
2cH=C (CH
3)
2time, described method comprises the steps:
A) by colourless to percolate for Cortex Garciniae oliganthae leaf sherwood oil seepage pressure effects, diacolation slag is obtained;
B) by colourless to percolate with 90% aqueous ethanolic solution seepage pressure effects for the diacolation slag of step a) gained, reduction vaporization percolate, obtains extract;
C) by step b) extract of gained is with water dissolution, and be extracted with ethyl acetate, reduction vaporization extraction liquid, obtains extract;
D) by step c) the extract chloroform of gained and methyl alcohol dissolves according to the mixing solutions that the volume ratio of 1:1 is formed and mixes thoroughly with proper silica gel, except being added on the silicagel column of 20 times amount after desolventizing, with the mixing solutions gradient elution successively that methylene dichloride and methyl alcohol are formed according to the volume ratio of 1:0 to 1:1, collect elutriant respectively, through TLC thin-layer chromatography after every part of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtains five components by elution order;
E) by steps d) in first component obtaining by MCI post, with 30% aqueous ethanolic solution, 60% aqueous ethanolic solution, 90% aqueous ethanolic solution, 95% aqueous ethanolic solution wash-out successively, collect elutriant respectively, through TLC tlc analysis after every part of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtains 11 components by elution order;
F) by step e) in the tenth component obtaining pass through gel column, with the mixing solutions wash-out that chloroform and methyl alcohol are formed according to the volume ratio of 1:1, collect elutriant respectively, through TLC tlc analysis after every part of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtains four components by elution order;
G) by step f) in second component obtaining by pressing preparative chromatography in ODS, with the mixing solutions gradient elution successively that methyl alcohol and water are formed according to the volume ratio of 30:70 to 100:0, collect elutriant respectively, through TLC tlc analysis after every part of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtains ten components by elution order;
H) by step g) in the 6th component methanol gel column purification, obtain target compound.
A fourth aspect of the present invention there is provided a kind of preparation method of compd B, and described method comprises the steps:
A) by substantially colourless to percolate for Cortex Garciniae oliganthae leaf sherwood oil seepage pressure effects, reduction vaporization percolate, obtains extract;
B) by step, a) the extract ethanol of gained and water are added on MCI post after dissolving according to the mixing solutions that the volume ratio of 1:1 is formed, with 30% aqueous ethanolic solution, 60% aqueous ethanolic solution, 90% aqueous ethanolic solution, 95% aqueous ethanolic solution wash-out successively, collect elutriant respectively, through TLC tlc analysis after every part of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtains five components by elution order;
C) by step b) in the 3rd component of gained by the middle pressure preparative chromatography of ODS, with the mixing solutions gradient elution successively that methyl alcohol and water are formed according to the volume ratio of 30:70 to 100:0, collect elutriant respectively, through TLC tlc analysis after every part of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtains ten components by elution order;
D) by step c) in the 5th component methanol gel column purification obtaining, obtain target compound.
A fifth aspect of the present invention there is provided a kind of pharmaceutical composition of anti-curing oncoma, and described composition comprises above-mentioned compd A or the compd B for the treatment of significant quantity, or its pharmacy acceptable salt, hydrate or prodrug.
In a preference, described tumour be selected from prostate cancer, liver cancer, lung cancer and colorectal carcinoma one or more.
A sixth aspect of the present invention there is provided above-claimed cpd A or compd B, or its pharmacy acceptable salt, hydrate or prodrug are preparing the application in tumor cell Cycle Arrest inductor.
In a preference, described tumour cell be selected from Human Prostate Cancer Cells PC-3, human liver cancer cell HepG2, Non-small cell lung carcinoma cell A549 and human colon cancer cell HT-29 one or more.
A eighth aspect of the present invention there is provided above-claimed cpd A or compd B, or the application in the medicine preparing prevention or treatment tumour or healthcare products of its pharmacy acceptable salt, hydrate or prodrug.
In a preference, described tumour be selected from prostate cancer, liver cancer, lung cancer and colorectal carcinoma one or more.
The details of all respects of the present invention is able to detailed description by chapters and sections subsequently.By hereafter and the description of claim, feature of the present invention, object and advantage will be more obvious.
Accompanying drawing illustrates:
The IC50 value of Fig. 1 OliganthinI, OliganthinH, OliganthoneB inhibition tumor cell growth.
Embodiment
Appearance of the present invention unexpected to find based on such one: the two class Xanthone compounds extracted from Cortex Garciniae oliganthae can significantly suppress the growth of kinds of tumor cells and can block cell cycle of inducing tumor cell.Therefore, compd A and B, specifically referring to that compound OliganthinI, OliganthinH, OliganthoneB are expected to develop becomes a kind of medicine preventing or treat tumour.
And then the present invention provide firstly a kind of compd A of having structure formula I and have the compd B of having structure formula II of having, specific as follows:
Wherein R is selected from methyl or-CH
2cH
2cH=C (CH
3)
2.
When R is methyl, compound is OliganthinI, molecular formula: C
28h
30o
7, molecular weight: 478, structural formula (I-1) is as follows:
OliganthinI，
When R is-CH
2cH
2cH=C (CH
3)
2time, compound is OliganthinH, molecular formula: C
33h
38o
7, molecular weight: 546, structural formula (I-2) is as follows:
OliganthinH，
Compd B called after OliganthoneB, molecular formula: C
29h
32o
7, molecular weight: 492, structure formula II is as follows:
B(OliganthoneB)
Present invention also offers all accordingly pharmaceutically acceptable salt of above-claimed cpd, hydrate or prodrug.These salt can be formed by part (such as, amido) positively charged in compound and electronegative (such as, the trifluoracetic acid) with opposite-sign; Or formed by part (such as, carboxyl) electronegative in compound and positive charge (such as, sodium, potassium, calcium, magnesium).Compound can contain a nonaromatic double bond, has one or more asymmetric center.So these compounds can exist as racemic mixture, independent enantiomer, independent diastereomer, non-enantiomer mixture, cis or trans-isomer(ide).All these isomer are all expected.Described " structural formula is respectively (I-1), (I-2), (II) the prodrug of compound " usually refer to a kind of material respectively, after using by appropriate means, metabolism or chemical reaction can be carried out and be transformed at least one compound or its salt that structural formula is respectively (I-1), (I-2), (II) respectively in subject.
Structural formula of the present invention is respectively (I-1), (I-2), (II) compound obtain as alcohol extracting, chromatography etc. extract from the plants such as Cortex Garciniae oliganthae by the ordinary method of this area, also buy by commercial sources or utilize marketable material, being obtained by compou nd synthesis method traditional in prior art synthesis.Those of ordinary skill in the art can synthesize compound of the present invention according to existing known technology.The compound of synthesis can be further purified further by modes such as column chromatography, high performance liquid chromatography or crystallizations.
Synthetic chemistry transformation, protection functional group methodology (protect or go protection) are helpful to synthesis application compound, and be known technology of the prior art, as R.Larock, ComprehensiveOrganicTransformations, VCHPublishers (1989); T.W.GreeneandP.G.M.Wuts, ProtectiveGroupsinOrganicSynthesis, 3
rded., JohnWileyandSons (1999); L.FieserandM.Fieser, FieserandFieser ' sReagentsforOrganicSynthesis, JohnWileyandSons (1994); Have open in andL.Paquette, ed., EncyclopediaofReagentsforOrganicSynthesis, JohnWileyandSons (1995).
The propagation that structural formula of the present invention is respectively (I-1), (I-2), the compound of (II) or its pharmacy acceptable salt, hydrate or prodrug can suppress various human tumour cell effectively, so compound of the present invention or its pharmacy acceptable salt, hydrate or prodrug can be used for preparing anti-tumor drug.
Present invention also offers a kind of composition, said composition comprises compound of the present invention or its pharmacy acceptable salt, hydrate or prodrug, and with pharmaceutically acceptable carrier, said composition can be used for treating tumour.
Present invention also offers a kind of pharmaceutical preparation, this pharmaceutical preparation comprises one or more compounds of the present invention or its pharmacy acceptable salt, hydrate or prodrug.This pharmaceutical preparation can be used for treating tumour.
Structural formula of the present invention is respectively (I-1), (I-2), the compound of (II) or its pharmacy acceptable salt, hydrate or the prodrug content in composition or pharmaceutical preparation such as 0.0001-50wt%; Preferably 0.001-30wt%; More 0.01-20wt%.
The consumption of the composition of the present invention for the treatment of significant quantity is between 0.001-500mg/kg body weight/day, and any consumption within above-mentioned scope is all significant quantity of the present invention.Preferably, the consumption of composition of the present invention is between 0.005-300mg/kg body weight/day; Preferred, the consumption of composition of the present invention is between 0.01-100mg/kg body weight/day.Described " treatment significant quantity " can be used for single drug or the drug combination treatment of relative disease.One of skill in the art can understand, and the consumption when actual administration can higher or lower than above-mentioned dosage range.Can by the impact of factors for " the treatment significant quantity " of a certain object (as Mammals-people) and concrete treatment plan, comprise the judgement etc. of the drug activity of compound used therefor or its prodrug, age of administration object, body weight, generalized case, sex, diet, administration time, disease susceptibility, disease process and treating physician.Described " treatment " refers to the compound giving body (containing tumour, have the symptom of tumour or have the omen of tumour) structural formula of the present invention and be respectively (I-1), (I-2), (II), to treat, to alleviate, to slow down, to change, to cure, to affect, to improve its tumour, the symptom of tumour or the omen of tumour.
Structural formula of the present invention is respectively (I-1), (I-2), the compound of (II) or its pharmacy acceptable salt, hydrate or prodrug or its composition or its pharmaceutical preparation can by the administrations such as oral, intravenously, intramuscular, subcutaneous, nasal cavity, internal rectum.Solid carrier is as starch, lactose, phosphoric acid glycol, Microcrystalline Cellulose, brown sugar and white bole, and liquid carrier is as sterilized water, polyoxyethylene glycol, nonionic surface active agent and edible oil (as Semen Maydis oil, peanut oil and sesame oil), as long as be applicable to the characteristic of activeconstituents and required specific administration mode.In pharmaceutical compositions, normally used adjuvant also can advantageously be included, and e.g., seasonings, pigment, sanitas and antioxidant are as vitamin-E, vitamins C, BHT and BHA.
Structural formula of the present invention is respectively (I-1), (I-2), (II) compound also can parenteral or intraperitoneal administration.Also solution or the suspension of these active compounds (as free alkali or pharmacy acceptable salt) can be prepared in the water being suitably mixed with tensio-active agent (as hydroxypropylcellulose).Also can prepare dispersion liquid in glycerine, polyoxyethylene glycol and the mixture in oil thereof.Under conventional storage and working conditions, contain sanitas in these preparations to prevent microbial growth.
The medicament forms being applicable to inject comprises: aseptic aqueous solution or dispersion liquid and aseptic powder (for extemporaneous preparation of sterile injection liquid or dispersion liquid).In all situations, these forms must be aseptic and must be that fluid is to be easy to syringe displacement fluids.Must be stable under conditions of manufacture and storage, and microorganism must be able to be prevented as the pollution of bacterium and fungi and impact.Carrier can be solvent or dispersion medium, wherein containing, for example water, alcohol, their suitable mixture and vegetables oil.
The experimental technique of unreceipted actual conditions in the following example, the usually conveniently conditioned disjunction condition of advising according to manufacturer.Unless otherwise indicated, otherwise all percentage ratio, ratio, ratio or number by weight.
Unless otherwise defined, all specialties used in literary composition and scientific words and one skilled in the art the same meaning be familiar with.In addition, the method that any to described content is similar or impartial and material all can be applicable in the inventive method.The use that better implementation method as herein described and material only present a demonstration.
The above-mentioned feature that the present invention mentions, or the feature that embodiment is mentioned can arbitrary combination.All features that patent specification discloses can with any composition forms and use, each feature disclosed in specification sheets, anyly can provide identical, alternative characteristics that is impartial or similar object replaces.Therefore apart from special instruction, the feature disclosed is only general example that is impartial or similar features.
Embodiment 1 is extracted and is identified OliganthinI, OliganthoneB and OliganthinH from Cortex Garciniae oliganthae leaf
1.1 experiment material
Cortex Garciniae oliganthae picks up from Hainan Province in September, 2013, and plant is through Agricultural University Of South China doctor Zhang Rongjing qualification.Plant sample is stored in Shanghai Univ. of Traditional Chinese Medicine's Innovative TCMs laboratory.
1.2 test method
At room temperature, get Cortex Garciniae oliganthae leaf powder (2.4 kilograms), substantially colourless to percolate with sherwood oil seepage pressure effects, reduction vaporization percolate, obtains sap green extract (A) 30 grams; The dregs of a decoction continue substantially colourless to percolate with 90% ethanol percolate extraction, and reduction vaporization percolate, obtains sap green extract (B) 460 grams.
Be added on MCI post after extract A alcohol-water mixing solutions is dissolved, with 30% aqueous ethanolic solution, 60% aqueous ethanolic solution, 90% aqueous ethanolic solution, 95% aqueous ethanolic solution wash-out successively, by 500 milliliters every bottle collections in elution process, through TLC tlc analysis after every bottle of elutriant reduction vaporization, by analytical results, eluate identical for the main point that TLC thin layer plate shows is merged, obtain 5 components, wherein first eluted first component is component 1 (A1), is arranged in order and obtains component 1 to component 5 (A1-A5).
Component 2 (A2) (4.0 grams) is by pressing preparative chromatography in ODS, with methanol/water gradient system (30:70 to 100:0, volume/volume) wash-out successively, elutriant is by 100 milliliters every bottle collections, through tlc analysis after every bottle of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtain 13 components, be component 1 (A2.1) by the first eluted component of elution order, be arranged in order and obtain component 1 to component 13 (A2.1-A2.13).Wherein component 11 (A2.11) (0.7 gram) methanol gel column purification obtains OliganthinI (200 milligrams).
Extract A be separated on MCI post the component 3 (A3) (3.8 grams) that obtains by ODS in press preparative chromatography, with methanol/water gradient system (30:70 to 100:0, volume/volume) wash-out successively, by 100 milliliters every bottle collections in sepn process, through tlc analysis after every bottle of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtain 10 components, be component 1 (A3.1) by the first eluted component of elution order, be arranged in order and obtain component 1 to component 10 (A3.1-A3.10).Wherein component 5 (A3.5) (40 milligrams) methanol gel column purification obtains OliganthoneB (2.6 milligrams).
By extract B with water dissolution, be extracted with ethyl acetate, reduction vaporization extraction liquid, obtain sap green extract 286 grams.This extract chloroform-methanol mixing solutions dissolves and mixes thoroughly with proper silica gel, except being added on the silicagel column of 20 times amount after desolventizing, with methylene chloride-methanol (1:0 to 1:1, volume/volume) gradient elution successively, by 500 milliliters every bottle collections in elution process, after every bottle of elutriant reduction vaporization, through TLC tlc analysis, eluate identical for the main point that TLC thin layer plate shows is merged, obtain five components, be component 1 (B1) by the first eluted component of elution order, be arranged in order and obtain component 1 to component 5 (B1-B5).Wherein component 1 (B1) (24 grams) is by MCI post, use 30% aqueous ethanolic solution, 60% aqueous ethanolic solution, 90% aqueous ethanolic solution, 95% aqueous ethanolic solution wash-out successively, by 250 milliliters every bottle collections in elution process, through TLC tlc analysis after every bottle of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtain 11 components, be component 1 (B1.1) by the first eluted component of elution order, be arranged in order and obtain component 1 to component 11 (B1.1-B1.11).Wherein component 10 (B1.10) (4.8 grams) passes through gel column, with chloroform-methanol (1:1, volume/volume) wash-out, elution process is by 20 milliliters every bottle collections, through TLC tlc analysis after every bottle of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtain four components, be component 1 (B1.10.1) by the first eluted component of elution order, be arranged in order and obtain component 1 to component 4 (B1.10.1-B1.10.4), wherein component 2 (B1.10.2) (4 grams) is by pressing preparative chromatography in ODS, with methanol/water gradient system (30:70 to 100:0, volume/volume) wash-out successively, by 100 milliliters every bottle collections in elution process, through TLC tlc analysis after every bottle of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtain ten components, be component 1 (B1.10.2.1) by the first eluted component of elution order, be arranged in order and obtain component 1 to component 10 (B1.10.2.1-B1.10.2.10), wherein component 6 (B1.10.2.6) (540 milligrams) obtains OliganthinH (500mg) with methanol gel column purification.
In this experiment, CHP20PMCIgel (75-150 μm, MitsubishiChemicalCoparation, Japan) selected by MCI post; Silica gel column chromatography selects Qingdao Marine Chemical Co., Ltd.'s column chromatography silica gel (200-300 order); TLC tlc analysis selects Yantai Jiang You silica gel development corporation, Ltd. HSGF254 tlc silica gel plate; In ODS, the standby chromatographic column of compacting selects reversed-phaseC18silicagel (50 μm, YMC, Kyoto, Japan); Gel column selects SephadexLH-20 (GEHealthcareBio-SciencesAB, Sweden) for filler.
OliganthinI is yellow, an amorphous powder, is C by high resolution mass spectrum determination molecular formula
28h
30o
7, be a new compound having no report.Its NMR data are as follows:
OliganthinH is yellow, an amorphous powder, is C by high resolution mass spectrum determination molecular formula
33h
38o
7, be a new compound having no report.Determine that the absolute configuration of OliganthinH is 8R configuration by single crystal X-ray diffraction.Its NMR data are as follows:
OliganthoneB is yellow, an amorphous powder, is C by high resolution mass spectrum determination molecular formula
28h
30o
7, be a new compound having no report, by the calculating of circular dichroism spectrum, determine that its absolute configuration is 5R, 7R, 10aS, 22R.Its NMR data are as follows:
1.3 experimental result
Be separated from Cortex Garciniae oliganthae and obtain compound OliganthinI, OliganthinH, OliganthoneB, through nuclear-magnetism and mass spectrometric detection, chemical structure is respectively as shown in (I-1), (I-2), (II):
Embodiment 2OliganthinI, OliganthinH, OliganthoneB suppress human tumor cells propagation
2.1 experiment material
Human Prostate Cancer Cells PC-3, human liver cancer cell HepG2, purchased from American ATCC company, Non-small cell lung carcinoma cell A549, people's normal cell lines of human liver Hl7702, Hong Kong Chinese University professor Lin Ge grants, human colon cancer cell HT-29, Tsing-Hua University professor Xu Naihan grants.
RPMI1640 purchased from American hyclone company, DMEM purchased from American Gibco company, foetal calf serum is purchased from German PAN company, and penicillin and Streptomycin sulphate are purchased from Hangzhou Ji Nuo company, and Taxol is purchased from German sigma company.
2.2 experimental technique
Non-small cell lung carcinoma cell A549, human liver cancer cell HepG2, liquid base is trained with the DMEM containing 10% foetal calf serum, 100U/ml penicillin and 100 μ g/ml Streptomycin sulphates, Human Prostate Cancer Cells PC-3, human colon cancer cell HT-29 and people's normal cell lines of human liver Hl7702 are with containing 10% foetal calf serum, the RPMI1640 of 100U/ml penicillin and 100 μ g/ml Streptomycin sulphates trains liquid base, in 37 DEG C, 5%CO
2and cultivate in the incubator of saturated humidity, go down to posterity with 0.25% tryptic digestion, take the logarithm vegetative period cell for experiment.
Human Prostate Cancer Cells PC-3, Non-small cell lung carcinoma cell A549, human liver cancer cell HepG2, human colon cancer cell HT-29 and people's normal cell lines of human liver Hl7702 (4000 cells/well) are inoculated in 96 orifice plates.Adding concentration gradient is respectively that OliganthinI, OliganthinH, OliganthoneB of 1.25 μMs, 2.5 μMs, 5 μMs, 10 μMs are in 96 orifice plates, Paclitaxel is as positive drug control group, after cultivating 72h, every hole adds 10ulMTT, and lucifuge is hatched 4h and dyeed.Then sucking-off substratum, add 150 μ lDMSO, use microplate reader to detect absorbance under 570nm, calculate the growth inhibition ratio of different concns with excel, mean value × 100 of growth inhibition ratio=(mean value of the mean value-treatment group of control group)/control.When the growth inhibition ratio of cell reaches 50%, the concentration of OliganthinI, OliganthinH, OliganthoneB is IC50 value.Experimental data all represents with mean+/-standard error.
2.3 experimental result
Result is as shown in table 1 and Fig. 1, and OliganthinI, OliganthinH, OliganthoneB act on PC-3, A549, HepG2, HT-29 and Hl7702 cell after 72 hours respectively, can the activity of obvious antiproliferative effect.Above result can prove OliganthinI, OliganthinH, OliganthoneB can concentration dependent ground inhibition tumor cell multiplication capacity.
The IC50 that OliganthinI, OliganthinH, OliganthoneB act on various human tumour 72h is as shown in the table.
The IC50 value of table 1OliganthinI, OliganthinH, OliganthoneB inhibition tumor cell growth
This experiment proves: OliganthinI, OliganthinH, OliganthoneB have the effect of inhibition tumor cell propagation, show that OliganthinI, OliganthinH, OliganthoneB have potential antitumor action, can as the medicine for the treatment of tumour or healthcare products.
Many aspects involved in the present invention have been done and have as above been set forth.It is to be understood, however, that put before not departing from spirit of the present invention, those skilled in the art can carry out equivalent change and modification to it, and described change and modification fall into the coverage of the application's claims equally.
Claims (10)
1. a compd A, or its pharmacy acceptable salt, hydrate or prodrug, is characterized in that, described compd A can extract and obtains and have having structure formula I from Cortex Garciniae oliganthae:
Wherein R is selected from methyl or-CH
2cH
2cH=C (CH
3)
2.
2. a compd B, or its pharmacy acceptable salt, hydrate or prodrug, is characterized in that, described compd B can extract and obtains and have having structure formula II from Cortex Garciniae oliganthae:
3. a preparation method for compd A as claimed in claim 1, is characterized in that, when R is methyl, described method comprises the steps:
A) by colourless to percolate for Cortex Garciniae oliganthae leaf sherwood oil seepage pressure effects, reduction vaporization percolate, obtains extract;
B) by step, a) the extract ethanol of gained and water are added on MCI post after dissolving according to the mixing solutions that the volume ratio of 1:1 is formed, with 30% aqueous ethanolic solution, 60% aqueous ethanolic solution, 90% aqueous ethanolic solution, 95% aqueous ethanolic solution wash-out successively, collect elutriant respectively, through TLC tlc analysis after every part of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtains five components by elution order;
C) by step b) in second component obtaining by pressing preparative chromatography in ODS, with the mixing solutions gradient elution successively that methyl alcohol and water are formed according to the volume ratio of 30:70 to 100:0, through TLC tlc analysis after every part of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtains 13 components by elution order;
D) by step c) in the 11 component methanol gel column purification obtaining, obtain target compound;
When R is-CH
2cH
2cH=C (CH
3)
2time, described method comprises the steps:
A) by colourless to percolate for Cortex Garciniae oliganthae leaf sherwood oil seepage pressure effects, diacolation slag is obtained;
B) by colourless to percolate with 90% aqueous ethanolic solution seepage pressure effects for the diacolation slag of step a) gained, reduction vaporization percolate, obtains extract;
C) by step b) extract of gained is with water dissolution, and be extracted with ethyl acetate, reduction vaporization extraction liquid, obtains extract;
D) by step c) the extract chloroform of gained and methyl alcohol dissolves according to the mixing solutions that the volume ratio of 1:1 is formed and mixes thoroughly with proper silica gel, except being added on the silicagel column of 20 times amount after desolventizing, with the mixing solutions gradient elution successively that methylene dichloride and methyl alcohol are formed according to the volume ratio of 1:0 to 1:1, collect elutriant respectively, through TLC thin-layer chromatography after every part of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtains five components by elution order;
E) by steps d) in first component obtaining by MCI post, with 30% aqueous ethanolic solution, 60% aqueous ethanolic solution, 90% aqueous ethanolic solution, 95% aqueous ethanolic solution wash-out successively, collect elutriant respectively, through TLC tlc analysis after every part of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtains 11 components by elution order;
F) by step e) in the tenth component obtaining pass through gel column, with the mixing solutions wash-out that chloroform and methyl alcohol are formed according to the volume ratio of 1:1, collect elutriant respectively, through TLC tlc analysis after every part of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtains four components by elution order;
G) by step f) in second component obtaining by pressing preparative chromatography in ODS, with the mixing solutions gradient elution successively that methyl alcohol and water are formed according to the volume ratio of 30:70 to 100:0, collect elutriant respectively, through TLC tlc analysis after every part of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtains ten components by elution order;
H) by step g) in the 6th component methanol gel column purification, obtain target compound.
4. a preparation method for compd B as claimed in claim 2, is characterized in that, described method comprises the steps:
A) by substantially colourless to percolate for Cortex Garciniae oliganthae leaf sherwood oil seepage pressure effects, reduction vaporization percolate, obtains extract;
B) by step, a) the extract ethanol of gained and water are added on MCI post after dissolving according to the mixing solutions that the volume ratio of 1:1 is formed, with 30% aqueous ethanolic solution, 60% aqueous ethanolic solution, 90% aqueous ethanolic solution, 95% aqueous ethanolic solution wash-out successively, collect elutriant respectively, through TLC tlc analysis after every part of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtains five components by elution order;
C) by step b) in the 3rd component of gained by the middle pressure preparative chromatography of ODS, with the mixing solutions gradient elution successively that methyl alcohol and water are formed according to the volume ratio of 30:70 to 100:0, collect elutriant respectively, through TLC tlc analysis after every part of elutriant reduction vaporization, eluate identical for the main point that TLC thin layer plate shows is merged, obtains ten components by elution order;
D) by step c) in the 5th component methanol gel column purification obtaining, obtain target compound.
5. a pharmaceutical composition for anti-curing oncoma, is characterized in that, described composition comprises the compound as claimed in claim 1 or 2 for the treatment of significant quantity, or its pharmacy acceptable salt, hydrate or prodrug.
6. pharmaceutical composition as claimed in claim 5, is characterized in that, described tumour be selected from prostate cancer, liver cancer, lung cancer and colorectal carcinoma one or more.
7. compound as claimed in claim 1 or 2, or its pharmacy acceptable salt, hydrate or prodrug are preparing the application in tumor cell Cycle Arrest inductor.
8. apply as claimed in claim 7, described tumour cell be selected from Human Prostate Cancer Cells PC-3, human liver cancer cell HepG2, Non-small cell lung carcinoma cell A549 and human colon cancer cell HT-29 one or more.
9. compound as claimed in claim 1 or 2, or the application in the medicine preparing prevention or treatment tumour or healthcare products of its pharmacy acceptable salt, hydrate or prodrug.
10. apply as claimed in claim 10, described tumour be selected from prostate cancer, liver cancer, lung cancer and colorectal carcinoma one or more.
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| CN107382950A (en) * | 2017-07-27 | 2017-11-24 | 上海中医药大学 | GaroliganthoneC and its pharmaceutical composition and purposes |
| CN113880857A (en) * | 2021-11-11 | 2022-01-04 | 山东大学 | Polyisopentenyl substituted cage-shaped xanthone compound and preparation method and application thereof |
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| CN113880857A (en) * | 2021-11-11 | 2022-01-04 | 山东大学 | Polyisopentenyl substituted cage-shaped xanthone compound and preparation method and application thereof |
| CN113880857B (en) * | 2021-11-11 | 2023-03-10 | 山东大学 | Polyisopentenyl substituted cage-shaped xanthone compound and preparation method and application thereof |
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