CN102311473B - Toonapubesic aldehyde and preparation method as well as application thereof - Google Patents
Toonapubesic aldehyde and preparation method as well as application thereof Download PDFInfo
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- CN102311473B CN102311473B CN201010216719A CN201010216719A CN102311473B CN 102311473 B CN102311473 B CN 102311473B CN 201010216719 A CN201010216719 A CN 201010216719A CN 201010216719 A CN201010216719 A CN 201010216719A CN 102311473 B CN102311473 B CN 102311473B
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Abstract
The invention relates to the technical field of medicines, and relates to toonapubesic aldehyde, which is served as a triterpene compound, has a novel framework, and is separated from Chinese toona ciliatavar.pubescens and a preparation method as well as application thereof to treatment of tumors and diabetes. The toonapubesic aldehyde has a structural formula which is shown in the specification. Experiments prove that the compound has obvious suppression activity on protein tyrosine phosphatase (CDC25B), cysteine and aspartate site specific protein hydrolase 3 (Caspase-3) and protein tyrosine phosphatase 1B (PTP1B) and can be used for preparing medicaments for treating tumor diseases and II-type diabetes and other complicating diseases caused thereby.
Description
Technical field
The present invention relates to medical technical field; More specifically; Relate to the novel triterpene compound hair toon aldehyde (toonapubesic aldehyde) of a kind of skeleton that extraction separation obtains from China hair toon (Toona ciliata var.pubescens), the invention still further relates to the preparation method of this compound.Biological activity test shows: this compound has remarkable inhibiting activity to tyrosine-phosphatase (CDC25B), halfcystine aspartic acid locus specificity proteolytic ferment 3 (Caspase-3) and protein-tyrosine-phosphatase 1B (PTP1B), can be used for preparing the medicine of treating tumour, II-type mellitus or its complication.
Background technology
The hair toon is a Meliaceae Cedrela plant, extensively is distributed in provinces such as Jiangxi, Hubei, Hunan, Guangdong, Guizhou and Yunnan; Be born in the mountain region thick forest or sparse woods of low height above sea level and intermediate altitude.
CDC25B is a member of CDC25 phosphoesterase family, and CDC25B activating cells cyclin-dependent kinase CDC2 is that mitotic division is essential, and CDC25B is present in the nucleus at splitted M and G1 phase, and transfers in the tenuigenin to S phase and G2 phase.CDC25B has proto-oncogene character, though its role in cancer takes place is not determined as yet, the suppressor factor that searches out differential high efficient can provide new instrument and means to cancer research.
Caspase-3 (claiming CPP32, apopain, Yama again) is the member in the Caspases family, is the key protein enzyme of mammalian cell apoptosis.It plays a part very important in the pathologic process of excessive relative disease died in many accent, and is relevant with diseases associated with inflammation such as nerve degenerative diseases such as senile dementia, Parkinson's disease, Huntington Chorea, the imbalance of vertebra cerebellum and acute liver damage, hepatitis, osteo-arthritis, rheumatic arthritis.Therefore, searching caspase-3 suppressor factor efficient, highly selective will be transferred the excessive relative disease of dying for treatment provides new approach.
PTP1B is first certified protein-tyrosine-phosphatase (protein tyrosinephosphatase); The experiment on mice of rejecting through PTP1B shows; PTP1B passes through the dephosphorization acidylate to insulin receptor, and then in regulating insulin sensitivity and metabolism of fat process, plays important effect.Thereby, optionally, highly active PTP1B suppressor factor has significant values in the treatment of mellitus and obesity.
Summary of the invention
The present invention is the novel triterpene compound hair toon aldehyde of skeleton that extraction separation obtains from China hair toon.Show that through pharmacological testing research this compound has the activity of inhibition to tyrosine-phosphatase (CDC25B), halfcystine aspartic acid locus specificity proteolytic ferment 3 (Caspase-3) and protein-tyrosine-phosphatase 1B (PTP1B).
Therefore, an object of the present invention is to provide new triterpene compound hair toon aldehyde.
Another object of the present invention provides the preparation method of said hair toon aldehyde.
Further purpose of the present invention provides the application of said hair toon aldehyde in the medicine of preparation tyrosine-phosphatase (CDC25B), halfcystine aspartic acid locus specificity proteolytic ferment 3 (Caspase-3) and protein-tyrosine-phosphatase 1B (PTP1B) suppressor factor, the further application in the medicine of preparation treatment tumour, II-type mellitus or its complication.
According to first purpose of the present invention, the present invention has found the triterpene compound hair toon aldehyde that skeleton is novel first from the hair toon, and its chemical structure is as follows:
According to second purpose of the present invention, the invention provides mao preparation method of toon aldehyde, its extraction separation from the hair toon obtains, and concrete steps are following:
Extract: China's hair toon bark is used methanol extraction, get CE after the gained extracting solution concentrates; This CE is water-soluble, use chloroform and n-butanol extraction successively after suspendible is even, the gained extraction liquid obtains chloroform medicinal extract and propyl carbinol medicinal extract respectively after concentrating;
Separate: chloroform medicinal extract carries out silica gel column chromatography, with the petrol ether/ethyl acetate gradient elution; Wherein, 70: 30 wash-out parts of petrol ether/ethyl acetate volume ratio, through Sephadex LH-20 gel filtration chromatography, with 1: 1 wash-out of chloroform/methanol volume ratio, elutriant with 90: 10 wash-outs of methanol-water, obtains a mao toon aldehyde again through preparation HPLC.
In above-mentioned preparation method, in extraction step, the method that said extraction is adopted is extracted for the methyl alcohol diacolation.
In above-mentioned preparation method, in separating step, the concentration of petrol ether/ethyl acetate gradient elution was followed successively by volume ratio 90: 10,80: 20 and 70: 30.
In above-mentioned preparation method, in separating step, the filler of the chromatographic column of said preparation HPLC is RP-18.
According to the 3rd purpose of the present invention, the invention provides mao purposes of toon aldehyde.
The present invention has carried out anticancer experiment in vitro to hair toon aldehyde.The experiment proof; Hair toon aldehyde has obvious restraining effect to tyrosine-phosphatase (CDC25B), halfcystine aspartic acid locus specificity proteolytic ferment 3 (Caspase-3) and protein-tyrosine-phosphatase 1B (PTP1B), and then can be used for treating tumour, II-type mellitus or its complication.External employing MTT method carries out tyrosine-phosphatase (CDC25B), halfcystine aspartic acid locus specificity proteolytic ferment 3 (Caspase-3) and protein-tyrosine-phosphatase 1B (PTP1B) are suppressed experiment.Hair toon aldehyde of the present invention can make up with pharmaceutically acceptable carrier, vehicle or auxiliary material, and then can be made into the pharmaceutical composition of treatment tumour, II-type mellitus or its complication.
Hair toon aldehyde of the present invention can obtain through separation and purification from plant; Also can be through the synthetic acquisition of chemical modification method well known to those skilled in the art.
Embodiment
The chemical structural formula (Arabic numeral in the structural formula are marks of carbon atom in the chemical structure) of the hair toon aldehyde of indication in following embodiment:
The preparation of 1 mao of toon aldehyde of embodiment
Extract: China hair toon bark (picking up from the Xinfeng County, Jiangxi Province) 4kg is carried out diacolation with methyl alcohol (5L) extract three times, get CE after the gained extracting solution concentrates; This CE is water-soluble, use (1L) and propyl carbinol (1L) to extract respectively successively three times after suspendible is even, the gained extraction liquid obtains chloroform medicinal extract (64g) and propyl carbinol medicinal extract (40g) respectively after concentrating.
Separate: chloroform medicinal extract carries out silica gel column chromatography, and with the petrol ether/ethyl acetate gradient elution, the concentration of gradient elution was followed successively by volume ratio 90: 10,80: 20 and 70: 30; Wherein, 70: 30 wash-out parts of petrol ether/ethyl acetate volume ratio are through Sephadex LH-20 gel filtration chromatography; With 1: 1 wash-out of chloroform/methanol volume ratio; Through preparation HPLC (filler of chromatographic column is RP-18),, obtain a mao toon aldehyde (8mg) again with 90: 10 wash-outs of methanol-water volume ratio.
Hair toon aldehyde, white powder, molecular formula is C
30H
48O
3 1H reaches
13C NMR data are seen table 1.
Table 1 mao toon aldehyde
1H with
13C NMR (ppm in CDCl
3)
The test of the antitumor and II-type diabetic activity of embodiment 2
1, laboratory sample and experimental technique
The preparation of sample solution: specimen is the pure article compound hair toon aldehyde of preparation in the foregoing description 1.Accurately take by weighing an amount of sample, the solution with DMSO is mixed with desired concn supplies active testing.
The acquisition of test proteins enzyme and activity test method:
Tyrosine-phosphatase (CDC25B) and protein-tyrosine-phosphatase 1B (PTP1B): adopt escherichia expression system to express the test that the catalyst structure domain albumen that obtains CDC25B and PTP1B is used for protease activity, its test activity methods and condition reference report [ActaPharmacologica Sinica (2009) 30:1359-1368].Halfcystine aspartic acid locus specificity proteolytic ferment 3 (Caspase-3) employing escherichia expression system obtains active Caspase-3 albumen and is used for the inhibitor activity test; Its testing method reference report [THEJOURNAL OF BIOLOGICAL CHEMISTRY VOL.283; NO.44; Pp.30205-30215, October 31,2008].
2, experimental result
See the following form 2.Compound hair toon aldehyde suppresses experimental result to tyrosine-phosphatase (CDC25B), halfcystine aspartic acid locus specificity proteolytic ferment 3 (Caspase-3) and protein-tyrosine-phosphatase 1B (PTP1B) and is respectively IC
50=0.96 μ g/mL, 7.62 μ g/mL, 2.81 μ g/mL show that it has the activity of inhibition to tyrosine-phosphatase (CDC25B), halfcystine aspartic acid locus specificity proteolytic ferment 3 (Caspase-3) and protein-tyrosine-phosphatase 1B (PTP1B).
Table 2
Enzyme type IC
50(μ g/mL)
CDC25B 0.96
Caspase-3 7.62
PTP1B 2.81
3, conclusion
Compound hair toon aldehyde has the activity of inhibition to tyrosine-phosphatase (CDC25B), halfcystine aspartic acid locus specificity proteolytic ferment 3 (Caspase-3) and protein-tyrosine-phosphatase 1B (PTP1B) under lower concentration.Therefore, hair toon aldehyde of the present invention can be used for preparing the medicine of treating tumour, II-type mellitus or its complication.
Claims (7)
1. the following triterpene compound hair toon aldehyde of chemical structural formula:
Hair toon aldehyde.
2. the preparation method of the described triterpene compound hair of claim 1 a toon aldehyde is characterized in that this method may further comprise the steps:
Extract: China's hair toon bark is used methanol extraction, get CE after the gained extracting solution concentrates; This CE is water-soluble, use chloroform and n-butanol extraction successively after suspendible is even, the gained extraction liquid obtains chloroform medicinal extract and propyl carbinol medicinal extract respectively after concentrating;
Separate: chloroform medicinal extract carries out silica gel column chromatography, with the petrol ether/ethyl acetate gradient elution; Wherein, 70: 30 wash-out parts of petrol ether/ethyl acetate volume ratio through Sephadex LH-20 gel filtration chromatography, with 1: 1 wash-out of chloroform/methanol volume ratio, again through preparation HPLC, with 90: 10 volume ratio wash-outs of methanol-water, obtain a mao toon aldehyde.
3. the preparation method of triterpene compound hair toon aldehyde according to claim 2 is characterized in that, in extraction step, the method that said extraction is adopted is extracted for the methyl alcohol diacolation.
4. the preparation method of triterpene compound hair toon aldehyde according to claim 2 is characterized in that in separating step, the concentration of petrol ether/ethyl acetate gradient elution was followed successively by volume ratio 90: 10,80: 20 and 70: 30.
5. the preparation method of triterpene compound hair toon aldehyde according to claim 2 is characterized in that, in separating step, the filler of the chromatographic column of said preparation HPLC is RP-18.
6. the purposes of triterpene compound hair toon aldehyde as claimed in claim 1 in the medicine of preparation tyrosine-phosphatase CDC25B, halfcystine aspartic acid locus specificity proteolytic ferment 3Caspase-3 and protein-tyrosine-phosphatase 1B PTP1B suppressor factor.
7. the purposes of triterpene compound hair toon aldehyde as claimed in claim 1 in the medicine of preparation treatment tumour, II-type mellitus or its complication.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201010216719A CN102311473B (en) | 2010-07-01 | 2010-07-01 | Toonapubesic aldehyde and preparation method as well as application thereof |
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| CN201010216719A CN102311473B (en) | 2010-07-01 | 2010-07-01 | Toonapubesic aldehyde and preparation method as well as application thereof |
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| CN102311473B true CN102311473B (en) | 2012-10-03 |
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| CN105153187A (en) * | 2015-10-09 | 2015-12-16 | 温州泓呈祥科技有限公司 | New diterpenoid as well as preparation method and medical application thereof |
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Non-Patent Citations (2)
| Title |
|---|
| Jian-Rong Wang et al..Protolimonoids and norlimonoids from the stem bark of Toona ciliata var. pubescens.《Organic & Biomolecular Chemistry》.2011,第9卷7685-7696. * |
| 卢海啸等.红楝子枝叶化学成分研究.《Journal of Chinese Medicinal Materials》.2009,第32卷(第10期),1539-1542. * |
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