CN107805269A - DICTYOPTERISINF and its prepare application in diabetes or obesity drug - Google Patents
DICTYOPTERISINF and its prepare application in diabetes or obesity drug Download PDFInfo
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- CN107805269A CN107805269A CN201710946502.7A CN201710946502A CN107805269A CN 107805269 A CN107805269 A CN 107805269A CN 201710946502 A CN201710946502 A CN 201710946502A CN 107805269 A CN107805269 A CN 107805269A
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- ptp1b
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- 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 13
- 239000003814 drug Substances 0.000 title claims abstract description 12
- 208000008589 Obesity Diseases 0.000 title claims abstract description 10
- 235000020824 obesity Nutrition 0.000 title claims abstract description 10
- 229940079593 drug Drugs 0.000 title abstract description 6
- 241000195493 Cryptophyta Species 0.000 claims abstract description 34
- 150000001875 compounds Chemical class 0.000 claims abstract description 14
- 241000024430 Dictyopteris undulata Species 0.000 claims abstract description 6
- 235000013402 health food Nutrition 0.000 claims abstract description 4
- -1 steroid compound Chemical class 0.000 claims abstract description 4
- 239000003405 delayed action preparation Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 1
- 230000002218 hypoglycaemic effect Effects 0.000 claims 1
- 239000003826 tablet Substances 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 abstract description 8
- 238000002474 experimental method Methods 0.000 abstract description 5
- 102000004169 proteins and genes Human genes 0.000 abstract description 5
- 108090000623 proteins and genes Proteins 0.000 abstract description 5
- 239000003801 protein tyrosine phosphatase 1B inhibitor Substances 0.000 abstract description 4
- 108090000371 Esterases Proteins 0.000 abstract description 3
- 239000008280 blood Substances 0.000 abstract description 3
- 210000004369 blood Anatomy 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 3
- 230000009467 reduction Effects 0.000 abstract description 2
- 101001087394 Homo sapiens Tyrosine-protein phosphatase non-receptor type 1 Proteins 0.000 abstract 2
- 102100033001 Tyrosine-protein phosphatase non-receptor type 1 Human genes 0.000 abstract 2
- 230000009286 beneficial effect Effects 0.000 abstract 1
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- 239000000284 extract Substances 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 16
- 238000010828 elution Methods 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 8
- 239000003208 petroleum Substances 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 102000002727 Protein Tyrosine Phosphatase Human genes 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 108020000494 protein-tyrosine phosphatase Proteins 0.000 description 6
- 102000004877 Insulin Human genes 0.000 description 5
- 108090001061 Insulin Proteins 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 229940125396 insulin Drugs 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- GJYVZUKSNFSLCL-UHFFFAOYSA-N dichloromethanol Chemical compound OC(Cl)Cl GJYVZUKSNFSLCL-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 3
- 238000011894 semi-preparative HPLC Methods 0.000 description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 238000001641 gel filtration chromatography Methods 0.000 description 2
- 238000002114 high-resolution electrospray ionisation mass spectrometry Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
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- 238000011084 recovery Methods 0.000 description 2
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- 239000000758 substrate Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- GXWUEMSASMVWKO-GNLHUFSQSA-N (4as,6ar,6as,6br,10s,12ar,14br)-10-[(2s,3r,4s,5s)-4,5-dihydroxy-3-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid Chemical compound O([C@@H]1[C@@H](O)[C@@H](O)CO[C@H]1O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CCC2C1(C)C)C)(C)CC[C@]1(CCC(C[C@@H]14)(C)C)C(O)=O)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GXWUEMSASMVWKO-GNLHUFSQSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- FYKHWKNFKLTGNX-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1.OC1=CC=C([N+]([O-])=O)C=C1 FYKHWKNFKLTGNX-UHFFFAOYSA-N 0.000 description 1
- 0 CC(C)C(CC[C@@](*)C(CC1)[C@@](*)(CCC([C@@]23)[C@@](C)(C=CC(O)=C4)C4=CC2=O)[C@@]13N)C=* Chemical compound CC(C)C(CC[C@@](*)C(CC1)[C@@](*)(CCC([C@@]23)[C@@](C)(C=CC(O)=C4)C4=CC2=O)[C@@]13N)C=* 0.000 description 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 102000002072 Non-Receptor Type 1 Protein Tyrosine Phosphatase Human genes 0.000 description 1
- 108010015847 Non-Receptor Type 1 Protein Tyrosine Phosphatase Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000018120 Recombinases Human genes 0.000 description 1
- 108010091086 Recombinases Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000005325 percolation Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
- A23L33/11—Plant sterols or derivatives thereof, e.g. phytosterols
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Botany (AREA)
- General Health & Medical Sciences (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention relates to pharmaceutical technology field, it is related to and new natural drug isolated, that there is function of blood sugar reduction is extracted from the wavy wing algae Dictyopteris undulata Holmes of China, the medicine is steroid compound wing algae element F (dictyopterisin F).External PTP1B suppresses experiment and shown, the compound for protein TYR esterase 1B (PTP1B) has inhibitory activity, therefore pharmaceutical preparation is can be made into as PTP1B inhibitor, for treating diabetes, obesity and its complication, the health food for being beneficial to diabetic or obese patient can also be manufactured.
Description
Technical field
The present invention relates to pharmaceutical technology field, and in particular to from the wavy wing algae Dictyopteris undulata of China
New natural drug Dictyopterisin F isolated, that there is function of blood sugar reduction are extracted in Holmes and its are preparing sugar
Purposes in urine disease or obesity drug.
Background technology
Diabetes (diabetes mellitus) are one group clinical comprehensive as caused by h and E factor interaction
Close disease.At present, diabetes are typically divided into two classes, I- patients with type Ⅰ DM (insulin-dependent diabetes mellitus, insulin-
Dependent diabetes mellitus, IDDM) and II- patients with type Ⅰ DM (Non-Insulin Dependent Diabetes Mellitus, non-
Insulin-dependent diabetes mellitus, NIDDM).90% above is II- patients with type Ⅰ DM in diabetes.
The characteristics of II- patients with type Ⅰ DM is that insulin sensitive tissues such as skeletal muscle, liver, adipose tissue support to insulin action
It is anti-.Protein-tyrosine-phosphatase (PTPases) GAP-associated protein GAP tyrosine phosphatase in insulin action path in statocyte
Effect in change level is increasingly taken seriously, and turns into the new way for the treatment of II- patients with type Ⅰ DM.PTPase includes big nation's cross-film
(receptor type) and intracellular (non-receptor type) enzyme, participate in a series of important life processes.At present, PTPase is led in insulin
Acceptor or acceptor metasomite influence the research of Normal insulin effect in road, be concentrated mainly on LAR-PTPase, SHPTP-2,
PTP1B。
PTP1B is first certified protein-tyrosine-phosphatase (protein tyrosine
Phosphatase), shown by the PTP1B experiments on mice rejected, PTP1B by being acylated to the dephosphorization of insulin receptor, and then
Very important effect is played in regulation insulin sensitivity and fat metabolic process.Thus, it is selective, high activity
PTP1B inhibitor has important value in the treatment of II- patients with type Ⅰ DM, obesity and its complication.
The content of the invention
The invention provides one kind, extraction is isolated, has drop blood from China's wavy wing algae (D.undulata)
New steroid compound --- the wing algae element F (dictyopterisin F) of sugar effect.Show through pharmacological testing research, the change
Compound has inhibitory activity to protein tyrosine phosphate 1B (PTP1B).
An object of the present invention is to provide new steroid compound wing algae element F.
The second object of the present invention is to provide the preparation method of the wing algae element F.
The third object of the present invention is to provide the purposes of the wing algae element F.Specifically, the wing algae element F is making
Application in the medicine of standby protein-tyrosine-phosphatase 1B (PTP1B) inhibitor, further preparing treatment diabetes, obesity
Application in the medicine or health food of disease and its complication.
According to first purpose of the present invention, the present invention is found that wing algae element F from wavy wing algae first, its chemistry
Structure is as follows：
According to second object of the present invention, the present invention provides the preparation method of the wing algae element F, and it is from wavy net
It is isolated in wing algae, comprise the following steps that：
1) extract medicinal extract is prepared
By the wavy wing algae (D.undulata) of freezing with ethanol routinely seepage pressure effects, extract solution is obtained, by extract solution
Be concentrated under reduced pressure recovery ethanol, obtains coarse extract；
2) isolate and purify
(1) above-mentioned coarse extract is dispersed in water into suspension, suspension extracted with ether, gained extract is concentrated to give
To extracted by ether medicinal extract；
(2) ether medicinal extract is subjected to silica gel column chromatography, successively with petroleum ether/acetone and dichloro methanol/methanol elution gradient,
Similar fraction is merged according to TLC colour developings and obtains 12 components (A-L)；Wherein component G is petroleum ether/acetone volume ratio 8:2 elutions
Part is through Sephadex LH-20 gel filtration chromatographies, with methylene chloride/methanol volume ratio 1:1 elution；Developed the color according to TLC and merge phase
4 components (G1-G4), component G2 (i.e. methylene chloride/methanol volume ratios 1 are obtained like fraction:1 elution volume is that 75~90mL is washed
De- part) again through silica gel column chromatography, with petroleum ether/acetone volume ratio 8:2 elutions, most afterwards through semi-preparative HPLC, with methanol/water
85:15 volume ratios elute, and obtain the compounds of this invention wing algae element F.
In above-mentioned preparation method, in extract medicinal extract step is prepared, the ethanol used that extracts is 95% ethanol.
In above-mentioned preparation method, in separating step, the concentration of petroleum ether/acetone gradient elution is followed successively by volume ratio
100:0、90:10、80:20、70:30、50:50 and 40:60.The concentration of dichloro methanol/methanol elution gradient is followed successively by volume ratio
70:30、60:40 and 50:50.
In above-mentioned preparation method, in separating step, the filler of the chromatographic column of the semi-preparative HPLC is RP-18.
According to third object of the present invention, the invention provides the wing algae element F to prepare PTP1B inhibitor, sugar
Urinate medicine, the purposes of obesity drug.And prepare purposes for diabetic or obese patient's health food.
In order to reach application purpose, tablet, capsule can be made, granule, oral liquid, sustained release preparation, controlled release preparation, receive
The form such as metric system agent or injection.
The present invention has carried out external PTP1B to gained wing algae element F and has suppressed experiment, the results showed that the compound is to PTP1B
With inhibitory activity.Therefore, can be used to prepare PTP1B inhibitor, for treating diabetes, obesity and its complication.
Brief description of the drawings
Fig. 1 is PTP1B inhibitory activity test philosophy figures.
Embodiment
Signified wing algae element F chemical structural formula (being of Arabic numerals in structural formula in examples below
Learn the mark of carbon atom in structure)：
Embodiment 1：The preparation of the wing algae element F
1. prepare wavy wing algae extract medicinal extract
(1) extract solution is prepared
Chinese wavy wing algae (D.undulata) (it is coastal the to pick up from Zhanjiang) 1.8kg (weight in wet base) of freezing is used respectively
The ethanol percolations of 5L 95% extract three times, each diacolation 2 days, merge extract solution；
(2) extract medicinal extract is prepared
Said extracted liquid is concentrated under reduced pressure in temperature≤45 DEG C recovery ethanol, obtains coarse extract 174.5g；
2. isolate and purify
1) above-mentioned coarse extract is scattered in 2L water into suspension, suspension extracted four times with ether (1.5L), gained
Extract is concentrated under reduced pressure to give extracted by ether medicinal extract (54.3g)；
2) ether medicinal extract is subjected to silica gel column chromatography, successively with petroleum ether/acetone and dichloro methanol/methanol elution gradient；
The concentration of petroleum ether/acetone gradient elution is followed successively by volume ratio 100:0、90:10、80:20、70:30、50:50 and 40:60, two
The concentration of chloromethane alcohol/methanol elution gradient is followed successively by volume ratio 70:30、60:40 and 50:50.Similar stream is merged according to TLC colour developings
Part obtains 12 components (A-L)；
3) component G is petroleum ether/acetone volume ratio 8:2 elution fractions are through Sephadex LH-20 gel filtration chromatographies【Chromatography
Post specification：3.1 (diameter) × 120 (length) cm；Sephadex LH-20 gel dry weights：150g】, with methylene chloride/methanol body
Product ratio 1:1 elution, similar fraction is merged according to TLC colour developings and obtains 4 components (G1-G4)；
4) component G2, i.e. methylene chloride/methanol volume ratio 1:1 elution volume is 75~90mL elution fractions, then through silica gel
Column chromatography, with petroleum ether/acetone volume ratio 8:2 elutions, most afterwards through semi-preparative HPLC (filler of chromatographic column is RP-18), with
Methanol/water volume ratio 85:15 elutions, flow velocity 3.5mL/min, retention time 28.2min, obtain the compounds of this invention wing
Algae element F, is identified as noval chemical compound.
3. Structural Identification
Routinely through the various modern spectral technique such as NMR, HRESIMS, UV and IR, it is determined that compound wing algae element F's
Chemical constitution, its physicochemical property are as follows：
White powder, molecular formula C29H46O3；
Specific rotatory power
Ultraviolet spectra UV (MeOH) λmax(logε):236(3.58)nm；
Infrared spectrum IR (KBr) νmax:3428,1665,1548,1490,1327,1217,1032cm–1；
High resolution mass spectrum HR-ESI-MS m/z 465.3347 [M+Na]+(calcd for C29H46O3Na,465.3345)；
Proton nmr spectra1H NMR (600MHz) and carbon-13 nmr spectra13C NMR (150MHz) data are shown in Table 1.
Wing algae element F described in table 11H and13C NMR(ppm in CDCl3)
Embodiment 2：The test of PTP1B inhibitory activity
Test philosophy：See Fig. 1.Using molecular biology method people's source protein TYR phosphoric acid is expressed in E. coli system
Esterase 1B (hPTP1B) catalyst structure domain, it is purified after hPTP1B recombinant proteins can hydrolyze substrate p-nitrophenyl phosphoric acid (p-
Nitrophenyl phosphate, pNPP) phosphatide key, obtain yellow soluble product p-nitrophenol (p-
Nitrophenol), the product has very strong light absorbs at 410nm, therefore can directly detect the change of light absorbs at 410nm
Change and observe the suppression situation of the activity change and compound of enzyme to enzymatic activity.
The live body system of standard：10mM Tris.Cl tri- (methylol) aminomethane hydrochloride), pH 7.6,10mM
PNPP, 2%DMSO, 100nM hPTP1B.
Observation index：Dynamic measure wavelength is the light absorbs at 410nm, and the time is 3 minutes, and its kinetic curve one-level is anti-
Activity index of the slope answered as enzyme.
Test method：Protein-tyrosine-phosphatase PTP1B for screening is from expression in escherichia coli and purified
Gst fusion protein.Using ultraviolet suitable substrates p-nitrophenyl phosphoric acid (pNPP), active suppression of the observation various concentrations to recombinase
Make and use, with the medicinal effects of preliminary assessment compound.Sample is dissolved in DMSO before use and is made into debita spissitudo, 3 times dilute, and 7
Individual dilution factor, three wells is set, takes 2 μ L samples solution to add 96 orifice plates, then adds 88 μ L assay mix (assay
Buffer, pNPP, H2O), 10 μ L PTP1B are added.It is at 410nm that 96 orifice plates are placed in into dynamic detection wavelength on VERSAmax
Absorbance value is detected, the time is 3 minutes.
The judge and explanation of experimental result：
The selection result be when compound concentration is 20 μ g/ml to the percent inhibition of enzymatic activity, when inhibiting rate is higher than 50%,
Routinely screening (by detected diluted chemical compound of the inhibiting rate higher than 50% into different concentration, is carried out according to above-mentioned method of testing
Reaction, all experiments are respectively provided with multiple holes) draw IC50, the IC of positive control oleanolic acid50For 2.74 ± 0.20 μM.
Experimental result：ICs of the compounds of this invention wing algae element F to PTP1B enzyme inhibition activities50For 38.15 ± 6.60 μM.
Experiment conclusion：Pass through molecular biology test, it can be seen that compound wing algae element F is to protein tyrosine esterase 1B
(PTP1B) there is inhibitory activity.Therefore, wing algae element F of the invention can be used for preparing diabetes, obesity and its complication
In medicine.
Claims (4)
- A kind of 1. steroid compound wing algae element F with hypoglycemic effect, it is characterised in that：With following chemical constitution：
- 2. wing algae element F according to claim 1, it is characterised in that：Described compound is from entoilage algae section brown alga ripple Isolated in shape wing algae, wavy wing algae scientific name is Dictyopteris undulata Holmes.
- 3. wing algae element F according to claim 1, it is characterised in that：As treatment diabetes, obesity and its complication The active component of medicine, it can be made into tablet, capsule, granule, oral liquid, sustained release preparation, controlled release preparation, nanometer formulation or injection Agent.
- 4. wing algae element F according to claim 1, it is characterised in that：As the active component of health products, for preparing sugar Urinate patient or obese patient's health food.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107722096A (en) * | 2017-10-11 | 2018-02-23 | 南昌大学 | A kind of steroid natural drug with antitumor action and its production and use |
| CN107746421A (en) * | 2017-10-11 | 2018-03-02 | 南昌大学 | Compound DICTYOPTERISINF and its application in antineoplastic is prepared |
| CN112159450A (en) * | 2020-10-02 | 2021-01-01 | 三味本草(北京)天然药物科技有限公司 | Steroid compound from white peony root and application thereof in treating diabetes |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107722096A (en) * | 2017-10-11 | 2018-02-23 | 南昌大学 | A kind of steroid natural drug with antitumor action and its production and use |
| CN107746421A (en) * | 2017-10-11 | 2018-03-02 | 南昌大学 | Compound DICTYOPTERISINF and its application in antineoplastic is prepared |
-
2017
- 2017-10-11 CN CN201710946502.7A patent/CN107805269A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107722096A (en) * | 2017-10-11 | 2018-02-23 | 南昌大学 | A kind of steroid natural drug with antitumor action and its production and use |
| CN107746421A (en) * | 2017-10-11 | 2018-03-02 | 南昌大学 | Compound DICTYOPTERISINF and its application in antineoplastic is prepared |
Non-Patent Citations (1)
| Title |
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| 洪涤等: "齐墩果酸的PTP1B构效关系研究", 《有机化学》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107722096A (en) * | 2017-10-11 | 2018-02-23 | 南昌大学 | A kind of steroid natural drug with antitumor action and its production and use |
| CN107746421A (en) * | 2017-10-11 | 2018-03-02 | 南昌大学 | Compound DICTYOPTERISINF and its application in antineoplastic is prepared |
| CN107746421B (en) * | 2017-10-11 | 2019-11-15 | 南昌大学 | Compound DICTYOPTERISIN F and its application in preparation of anti-tumor drugs |
| CN107722096B (en) * | 2017-10-11 | 2020-04-03 | 南昌大学 | Natural steroid medicine with anti-tumor effect and its prepn and use |
| CN112159450A (en) * | 2020-10-02 | 2021-01-01 | 三味本草(北京)天然药物科技有限公司 | Steroid compound from white peony root and application thereof in treating diabetes |
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