CN102964328A - Isopentene isoflavanone compound as well as preparation method and application of compound - Google Patents
Isopentene isoflavanone compound as well as preparation method and application of compound Download PDFInfo
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- CN102964328A CN102964328A CN2012105469064A CN201210546906A CN102964328A CN 102964328 A CN102964328 A CN 102964328A CN 2012105469064 A CN2012105469064 A CN 2012105469064A CN 201210546906 A CN201210546906 A CN 201210546906A CN 102964328 A CN102964328 A CN 102964328A
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Abstract
The invention relates to a natural medicine, and in particular relates to a novel isoflavanone isoflavanone compound in wild peanuts as well as a preparation method and application of the compound. The novel isoflavanone isoflavanone compound provided by the invention has a structural formula shown in a formula (I). The preparation method comprises the following steps of: a, crushing; b, refluxing and extracting; c, concentrating; d, extracting; and e, separating. The novel isoflavanone isoflavanone compound shown in the formula (I) has a remarkable inhibition function to a human cervical carcinoma, human chronic myeloid leukemia or human acute myelogenous leukemia cell strain, has a better anti-cancer activity, and can be used as an anti-cancer active component or lead compound. The novel isoflavanone isoflavanone compound can be a natural organic compound, is wide in raw material source, is simple in preparation process, is high in purity, is easily realized in subsequent industrialized production, is used for preparing a medicament for preventing or treating tumors, and is used for clinically treating human cervical carcinoma, human chronic myeloid leukemia or human acute myelogenous leukemia.
Description
Technical field
The present invention relates to a kind of natural drug, be specifically related to a kind of new isopentene group isoflavanone compounds and its preparation method and application in the wild kind beans.
Background technology
Cancer has developed into common disease, the frequently-occurring disease of serious harm people life, and same cardiovascular and cerebrovascular disease, diabetes are called as one of the world three large Deaths together.The World Health Organization issues in February, 2010 and reports, the whole world will have 7,600,000 people to die from cancer to estimate the current year, if the half-hearted preventing cancer of taking measures of people may be doubled on existing basis to the annual cancer mortality number in the year two thousand thirty whole world, reach 1,700 ten thousand.This tissue statistic data also shows just have 1 people to die from cancer in average per 8 deaths in the whole world at present, and this is more taller than the death toll summation that acquired immune deficiency syndrome (AIDS), tuberculosis and malaria cause.Therefore seeking effective cancer therapy drug has become the task of top priority.In cancer therapy drug research, the studies and clinical application of chemotherapeutics has been obtained remarkable progress.Although have strong cancer resistance, there are toxic side effect in the cancer therapy drug of chemosynthesis such as metal complexes platinum complex, organic germanium compounds etc., the defectives such as poorly water-soluble.In recent years, the researchist of China and foreign countries turns one's attention to herbal medicine, the ethnic drug of aboundresources, pure natural gradually, wishes therefrom to seek new cancer therapy drug.From herbal medicine, ethnic drug, found at present a series of natural anti-cancer drugs such as taxol, camptothecine, kind of harringtonine as medicinal materials, vincristine(VCR), podophyllotoxin, Elemenum Emulsion, and many new product listings have been arranged every year.These natural drugs have all showed good antitumour activity and have been widely used clinically, prove day by day that also screening antineoplastic drugs is a very promising direction from natural product.
Wild kind beans (Uraria clarkei Gagnep) are pulse family (Leguminosae) leopard cat tail bean plant (72 pages of " Chinese Plants will " the 41st volumes).This platymiscium whole world has 20 kinds approximately, is distributed in Tropical Africa, Asia and Australia, and China has 9 kinds.(Chen Yan thinks the elegant tinkling of pieces of jade, Wei Song according to document, Xu Xuejian. the research [J] of rabbit tail grass chemical ingredients. Chinese patent medicine, 2009,31 (2): 266-269) report, this platymiscium have the effects such as treatment infantile malnutrition, puerperal lactation deficiency, hemoptysis, hemorrhoid, the tuberculosis of cervical lymph nodes, venomous snake bite.Its chemical ingredients is mainly flavonoid compound, comprises the structure types such as flavones, isoflavones, isoflavanone.The multiple biological activitys such as that flavonoid compound has is antitumor, hypotensive, reducing blood-fat, Anti-bacterium, anti-HIV.The present invention attempts the antitumor action of isoflavanone compounds in the wild kind beans is done further further investigation, and in the hope of finding cytotoxic activity natural product wherein, antitumor drug efficient for screening, low toxicity provides foundation.
Summary of the invention
The object of the present invention is to provide a kind of new isopentene group isoflavanone compounds.
Another object of the present invention provides a kind of method of extracting the compounds of this invention from wild kind beans.
Further aim of the present invention is the application of the compounds of this invention in preparation prevention or medicine for treating tumor thing.
Further aim of the present invention is the application of the compounds of this invention in preparing prevention or treatment human cervical carcinoma, people's chronic myelogenous leukemia, human acute myeloid leukemia medicine.
Purpose of the present invention is achieved by following technical proposals.
Except as otherwise noted, the percentage ratio that adopts among the present invention is mass percent.
The present invention isolates a kind of new isopentene group isoflavanone compounds from wild kind beans, this compound has significant antitumour activity.
New isopentene group isoflavanone compounds of the present invention has the structural formula shown in the formula I:
The called after of this compound: (3
R)-8,5 ′ – diisoamyl thiazolinyl-5,2 '-dihydroxyl-7,4 '-dimethoxy isoflavanone ((3
R)-8,5 ′ – di-(
γ,
γ-dimethylallyl)-5,2 '-dihydroxyl-7,4 '-dimethoxyl-isoflavanone).
The invention provides a kind of preparation method of formula compound, the method adopts following steps:
A. pulverize: with getting meal after kind beanstalk dried and crushed of open country, for subsequent use;
B. refluxing extraction: the meal that makes among the step a with alcohol reflux four times, is merged ethanol extract, for subsequent use;
C. concentrated: get medicinal extract with carrying out concentrating under reduced pressure after the ethanol extract filtration that makes among the step b, for subsequent use;
D. extraction: the medicinal extract that makes among the step c is suspended in the water, extracts with propyl carbinol with sherwood oil, ethyl acetate successively, remove again solvent, get respectively sherwood oil, ethyl acetate and n-butyl alcohol extract, for subsequent use;
E. separate: with the petroleum ether extract that makes in the steps d through 100-200 order silica gel column chromatography, sherwood oil with volume ratio 30:1,20:1,10:1,5:1,2:1,1:1,0:1: ethyl acetate, gradient elution obtains Fr.1-Fr.7 totally 7 components, Fr.4 is through silica gel column chromatography, chloroform with volume ratio 98:2,97:3,96:4,95:5: the methyl alcohol gradient elution obtains component Fr.4A-4D.Fr.4C obtains formula I compound through sephadex LH-20 column chromatography methyl alcohol purifying.
The present invention has carried out the cytotoxic activity test to the formula compound, experimental result demonstrates good inhibition human cervical carcinoma, people's chronic myelogenous leukemia, human acute myeloid leukemia cell strain activity, can be new compound or lead compound that medical industry provides using value.
Beneficial effect
1, the formula I compound among the present invention has significant restraining effect to human cervical carcinoma, people's chronic myelogenous leukemia or human acute myeloid leukemia cell strain, points out it to have good antitumour activity, can be used as anticancer active constituent or lead compound.
2, the formula I compound among the present invention can be naturally occurring organic compound, and raw material sources are extensive, and compound preparation manipulation flow process is simple, and the compound purity that obtains is high, and suitability for industrialized production subsequently easily realizes.
Description of drawings
Fig. 1 is the structural formula of the compounds of this invention;
Fig. 2 is the compounds of this invention high resolution mass spectrum (HRESI-MS);
Fig. 3 be the compounds of this invention proton nmr spectra (
1H NMR);
Fig. 4 be the compounds of this invention carbon-13 nmr spectra (
13C NMR);
Fig. 5 is the DEPT spectrum of the compounds of this invention;
Fig. 6 is the HSQC Correlated Spectroscopy of the compounds of this invention;
Fig. 7 is the HMBC Correlated Spectroscopy of the compounds of this invention;
Fig. 8 is the ROESY Correlated Spectroscopy of the compounds of this invention;
Fig. 9 is the CD spectrum of the compounds of this invention.
Specific embodiment
By the following specific embodiment that provides and typically used embodiment, can further be well understood to the present invention.But this is not construed as limiting the scope of the present invention.
The preparation of compound
Material source: wild kind beans are adopted in Yunnan, are accredited as Uraria clarkei (Clarke) Gagnep. through the Tao Deding researcher of Kunming Inst. of Botany, Chinese Academy of Sciences, and sample is stored in Yunnan Institute for nationalitiesization and gives birth to institute sample shop.
Adopt following steps:
A. pulverize: the wild kind beanstalk dried and crushed of 10Kg is become the meal of particle diameter 0.1cm size, for subsequent use;
B. refluxing extraction: with the meal that makes among step a refluxing extraction 4 times under 70-74 ℃ temperature, each 2 hours, the ethanol 60Kg with 95% concentration extracts at every turn, merges ethanol extract, and was for subsequent use;
C, concentrated: the ethanol extract via hole diameter that step b is made is the filter paper filtering of 80-120 micron and carries out concentrating under reduced pressure with Rotary Evaporators under 50 ℃ temperature, to proportion be 1.2 o'clock, get medicinal extract 1025 g, for subsequent use;
D, extraction: 1025g medicinal extract is suspended in the 3000ml water, extract with 3000ml sherwood oil, 3000ml ethyl acetate and 3000ml propyl carbinol successively, every kind of solvent extraction 5 times, boil off solvent with Rotary Evaporators again, get respectively sherwood oil, ethyl acetate and n-butyl alcohol extract 100g, 70g, 200g.
E. separate: with the petroleum ether extract that makes in the steps d through 300 order silica gel column chromatographies, use volume ratio 30:1,20:1,10:1,5:1,2:1,1:1, the sherwood oil of 0:1: ethyl acetate, gradient elution obtains Fr.1-Fr.7 totally 7 components, Fr.1 is 15.1g, Fr.2 is 8.9g, and Fr.3 is 17.7g, and Fr.4 is 7.9g, Fr.5 is 5.8 g, Fr.6 is 9.7g, and Fr.7 is 14.3g, and Fr.4 is through silica gel column chromatography, with volume ratio 98:2,97:3,96:4, the chloroform of 95:5: methanol-eluted fractions, obtain Fr.4A-4D totally 4 components, Fr.4A is 1.2g, and Fr.4B is 0.3g, Fr.4C is 3.6g, and Fr.4D is 0.8g.Fr.4C obtains faint yellow amorphous powder 138 mg through sephadex LH-20 column chromatography 2300ml methyl alcohol purifying.
Embodiment 2:Different concentration ethanol solution extracts wild kind beans sample contrast experiment
Because the research report to wild kind beans chemical ingredients is few, so wish by using different concentration ethanol solution to extract wild kind beans sample, to find best ethanolic soln concentration.This is not that hint cannot be used other solvent extractions.
A, pulverizing: be ground into the meal of particle diameter 0.1-0.5 cm size after wild kind beanstalk dried, for subsequent use;
B, refluxing extraction: the meal that makes with step a under 70-74 ℃ temperature makes to extract solvent with the ethanol of 6 times of amount 70% concentration, the ethanol of 80% concentration and the ethanol of 95% concentration respectively, refluxing extraction 4 times, each 2 hours, merge respectively ethanol extract, for subsequent use;
C, concentrated: the different concentration ethanol extracting solution via hole diameter that respectively step b is made is the filter paper filtering of 80-120 micron and carries out concentrating under reduced pressure under 50 ℃ temperature, to proportion be 1.2 o'clock, get medicinal extract, for subsequent use;
D, extraction: the medicinal extract that respectively step c is made is suspended in 3 times of water gagings, 1 times of amount of water sherwood oil, water 1 times of amount ethyl acetate and 1 times of amount of water propyl carbinol extract successively, every kind of solvent extraction 5 times, merge the same solvent extract, use again Rotary Evaporators pressure reducing and steaming solvent, get respectively sherwood oil, ethyl acetate and n-butyl alcohol extract.
Experimental result shows with the ethanol of the ethanol of the ethanol of 70% concentration, 80% concentration and 95% concentration makes to extract solvent, the open country that obtains respectively kind beans acetic acid ethyl ester extract weight approaches, therefore do to extract solvent with the ethanol of 70% concentration, the ethanol of 80% concentration and the ethanol of 95% concentration, can obtain to contain equally the composition of formula I compound.
The wild kind beans different solvents extract extract yield table of table 1.
Embodiment 3
The Structural Identification of embodiment 1 resulting faint yellow amorphous powder
Described faint yellow amorphous powder (solvent is methyl alcohol), [
α] 22 D=-27.3 (
c=0.23, MeOH); UV (MeOH)
λ Max(log ε): 291 (2.96) nm; CD (
c=0.101, MeOH) λ (Δ ε) 258.5 (+0.435), 346 (+0.059); IR (KBr)
ν Max: 3360,1640,1601,1507,1453,1274,1108,1010 cm
-1; HRESI-MS (accompanying drawing 2) shows its quasi-molecular ion peak m/z 453.2158 [M+H]
+(calcd. 453.2232) determine that in conjunction with the NMR spectrum its molecular formula is C
27H
32O
6, degree of unsaturation is 12.
1H and
13C NMR (accompanying drawing 3, accompanying drawing 4 and accompanying drawing
5, attribution data sees Table-
1) show in the molecule 2 phenyl ring (3 methyne double key carbons are arranged on the phenyl ring) are arranged, 2 isopentene group (δ
C132.2,131.8,122.8,122.1,27.9,25.8,25.8,21.0,17.8,17.7), 1 carbonyl (δ
C197.0), 2 methoxyl group (δ
C55.9,55.4), 1 Oxymethylene (δ even
C69.5) and 1 methyne (δ
C45.0).In conjunction with HSQC Correlated Spectroscopy (accompanying drawing
6), and this compound of documents data susceptible of proof is the isoflavanone compounds that contains 2 isopentene groups; Further confirm that through HMBC relevant (accompanying drawing 7) C-7, C-4 ' position are substituted by methoxyl group, C-5, C-2 ' position are substituted by hydroxyl, and C-8, C-5 ' position are substituted by isopentene group.The absolute configuration of compound is by ROESY (accompanying drawing 8), CD spectrum (accompanying drawing 9) and and document (Tanaka T., Ohyama M., Iinuma M., Shirataki Y., Komatsu M., Burandt C.L. Isoflavonoids from
Sophora secundiflora,
S. arizonicaAnd
S. gypsophila.
Phytochemistry, 1998,48,1187-1193.; Slade D, Ferreira D, Marais JPJ. Circular dichroism, a powerful tool for the assessment of absolute configuration of flavonoids. Phytochemistry, 2005,66,2177-2215.) contrast turns out to be 3
R-configuration, the structure of compound finally obtain confirming that compound has the structural formula of formula I (such as accompanying drawing 1).。Confirm that by SCIFINDER database retrieval and literature query this compound is new compound.
Table 2. formula I compound
1H-and
13C-NMR (CDCl
3) data.
Embodiment 4
Described formula I antitumor activity of compound detects
Adopt improvement mtt assay assessing compound to the increment restraining effect of tumour cell
Get tumour cell suspension inoculation for subsequent use in 96 well culture plates, 90 μ L/ holes, the given the test agent of adding different concns behind continuation cultivation 24 h, 10 μ L/ holes, making its final concentration is 100,10,1,0.1,0.01 μ g/mL, and each concentration is all established 3 multiple holes.The positive contrast of cis-platinum (DDP), the negative contrast of equal-volume RPMI1640 substratum.Corresponding DMSO concentration is the solvent contrast when establishing simultaneously compound 100,10 μ g/mL, to eliminate the impact of DMSO cell growth.Continue to place 37 ℃ after the dosing, 5% CO
2Incubator is cultivated 72 h, and every hole adds MTT(5 mg/mL) 20 μ L, continue to cultivate 4 h, every hole adds three liquid [10%SDS-5% isopropylcarbinol-0.012 mol/L HCl(W/V/V)], 100 μ L Rong Xie formazans.Under 570 nm wavelength, measure the OD value in each hole with microplate reader.
Calculate cell increment inhibiting rate by following formula:
Inhibiting rate (%)=(OD value control wells-OD value dosing holes)/OD value control wells * 100%
Data statistic analysis: adopt Microsoft Excel 2003 to calculate inhibiting rate, adopt the logit method, SPSS11.5 software package calculation of half inhibitory concentration IC
50
Calculation of half inhibitory concentration IC
50, to the half-inhibition concentration (IC of human cervical carcinoma (Hela), people's chronic myelogenous leukemia cell strain (k562) and human acute myeloid leukemia cell strain (HL60)
50) measurement result is respectively 12.7 ± 2.6 μ g/ml, 18.4 ± 3.7 μ g/ml, 15.9 ± 3.1 μ g/ml show that compound of the present invention has preferably anti-tumor activity.
The above only is preferred embodiment of the present invention, and in order to limit the present invention, all any modifications of doing within the spirit and principles in the present invention are not equal to replacement and improvement etc., all should be included within protection scope of the present invention.
Claims (4)
1. isopentene group isoflavanone compounds is characterized in that having following structural formula (I):
。
2. the preparation method of described a kind of isopentene group isoflavanone compounds according to claim 1 is characterized in that the method adopts following steps:
A. pulverize: with getting meal after kind beanstalk dried and crushed of open country, for subsequent use;
B. refluxing extraction: the meal that makes among the step a with alcohol reflux four times, is merged ethanol extract, for subsequent use;
C. concentrated: get medicinal extract with carrying out concentrating under reduced pressure after the ethanol extract filtration that makes among the step b, for subsequent use;
D. extraction: the medicinal extract that makes among the step c is suspended in the water, extracts with propyl carbinol with sherwood oil, ethyl acetate successively, remove again solvent, get respectively sherwood oil, ethyl acetate and n-butyl alcohol extract, for subsequent use;
E. separate: with the petroleum ether extract that makes in the steps d through 100-200 order silica gel column chromatography, petroleum ether-ethyl acetate gradient elution with volume ratio 30:1,20:1,10:1,5:1,2:1,1:1,0:1 obtains Fr.1-Fr.7 totally 7 components, Fr.4 is through silica gel column chromatography, chloroform with volume ratio 98:2～95:5: methyl alcohol gradient elution, obtain component Fr.4A-4D, Fr.4C obtains formula (I) compound through sephadex LH-20 column chromatography methyl alcohol purifying.
3. described a kind of isopentene group isoflavanone compounds according to claim 1 is characterized in that the application of described isopentene group isoflavanone compounds in preparation prevention or medicine for treating tumor thing.
4. described a kind of isopentene group isoflavanone compounds according to claim 1 is characterized in that the application of described isopentene group isoflavanone compounds in preparation prevention or treatment human cervical carcinoma, people's chronic myelogenous leukemia, human acute myeloid leukemia medicine.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108822093A (en) * | 2018-06-08 | 2018-11-16 | 海南师范大学 | A kind of new prenyl isoflavones class compound and its preparation method and application |
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| CN101002841A (en) * | 2006-12-27 | 2007-07-25 | 中国科学院新疆理化技术研究所 | Effective components of rose, its preparing method and use |
| CN101434592A (en) * | 2008-12-19 | 2009-05-20 | 沈阳药科大学 | Novel flavonoid extracted from Maackia amurensis |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101002841A (en) * | 2006-12-27 | 2007-07-25 | 中国科学院新疆理化技术研究所 | Effective components of rose, its preparing method and use |
| CN101434592A (en) * | 2008-12-19 | 2009-05-20 | 沈阳药科大学 | Novel flavonoid extracted from Maackia amurensis |
Non-Patent Citations (1)
| Title |
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| TOSHIO，FUKAI;等: "Cytotoxic activity of low molecular weight polyphenols against human oral tumor cell lines", 《ANTICANCER RESEARCH》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108822093A (en) * | 2018-06-08 | 2018-11-16 | 海南师范大学 | A kind of new prenyl isoflavones class compound and its preparation method and application |
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