CN110105422A - A kind of uncaria indoles diterpene alkaloid and the preparation method and application thereof - Google Patents
A kind of uncaria indoles diterpene alkaloid and the preparation method and application thereof Download PDFInfo
- Publication number
- CN110105422A CN110105422A CN201910508550.7A CN201910508550A CN110105422A CN 110105422 A CN110105422 A CN 110105422A CN 201910508550 A CN201910508550 A CN 201910508550A CN 110105422 A CN110105422 A CN 110105422A
- Authority
- CN
- China
- Prior art keywords
- uncaria
- preparation
- indoles
- indoles diterpene
- diterpene alkaloid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
- C07J73/001—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom
- C07J73/003—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom by oxygen as hetero atom
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a kind of uncaria indoles diterpene alkaloid and the preparation method and application thereof, the uncaria indoles diterpene alkaloid has structure shown in Formulas I:
Description
Technical field
The invention belongs to extracted form natural plant fields, and in particular to a kind of uncaria indoles diterpene alkaloid and preparation method thereof
With application.
Background technique
Uncaria Uncaria rhynchophylla (Miq.) Jacks. is Rubiaceae (Rubiaceae) wild gambier
(Uncaria) the plant plant is one of main Original plant of traditional Chinese medicine uncaria, and medicinal part is buckle stem branch, has breath
Wind arresting convulsion, The flat liver of heat-clearing and other effects.A variety of indoles alkaloids is isolated from uncaria at present (based on rhynchophyllin).This hair
Bright to be extracted using alcohol reflux, binding silica gel column chromatography, high performance liquid chromatography prepare a kind of uncaria indoles of structure novel
Diterpene alkaloid compound, and test its cytotoxic activity.
Summary of the invention
The present invention provides a kind of uncaria indoles diterpene alkaloid or its pharmaceutically acceptable salt, it is characterised in that the hook
Rattan indoles diterpene alkaloid has structure shown in Formulas I:
Another embodiment of the present invention provides the preparation method of above-mentioned uncaria indoles diterpene alkaloid, it is characterised in that packet
Include following steps:
(1) dry uncaria buckle stem branch is crushed, after being extracted 10-12 hours with 95% alcohol reflux, filtering, filtrate are dense
Contract to obtain extract；
(2) extract that step (1) obtains is through chromatographic isolation up to the uncaria indoles diterpene alkaloid.
The preferred 20-100 mesh of crushing described in step (1), it is preferable to use 95% second for every kilogram of dry uncaria buckle stem branch
The preferred 8-10L of the dosage of alcohol；
The preferred silica gel column chromatography of step (2) chromatographic isolation is combined with high performance liquid chromatography preparation；Specially extract
First through silica gel column chromatography, stationary phase is 200-300 mesh silica gel, mobile phase using petroleum ether-ethyl acetate by 100:0,90:10,
80:20,70:30,60:40,50:50,40:60,30:70,20:80,10:90,0:100 gradient elution, each gradient collect 3
Column volume is prepared into the hook through high performance liquid chromatography after the fraction merging concentration that wherein 90:10 and 80:20 gradient elution obtains
Rattan indoles diterpene alkaloid；The high performance liquid chromatography prepares the chromatographic condition used: chromatographic column is Agilent Eclipse
XDB-C18,9.4 × 250mm, 5 μm, flow velocity 1.5mL/min, mobile phase MeOH:H2O=60:40.
Another embodiment of the present invention provides uncaria buckle stem branch in preparing the uncaria indoles diterpene alkaloid
Using.
Another embodiment of the present invention provides above-mentioned uncaria indoles diterpene alkaloid or its pharmaceutically acceptable salt exists
Prepare the application in anti-tumor drug.
Another embodiment of the present invention provides a kind of pharmaceutical composition, it is characterised in that described pharmaceutical composition is with above-mentioned
Uncaria indoles diterpene alkaloid or its pharmaceutically acceptable salt are as effective component.It is anti-that the pharmaceutical composition may also include other
Tumour medicine.The pharmaceutical composition may also include the auxiliary material that can pharmaceutically connect.
95% ethyl alcohol of the present invention refers to that volume fraction is 95% ethanol solution.
Detailed description of the invention
Fig. 1 is compound of formula I1H NMR(CDCl3, 600MHz) and figure；
Fig. 2 is compound of formula I1H NMRδHThe enlarged drawing of 7.9-7.0；
Fig. 3 is compound of formula I1H NMRδHThe enlarged drawing of 3.3-0.9；
Fig. 4 is compound of formula I13C NMR(CDCl3, 150MHz) and figure；
Fig. 5 is the MS figure of compound of formula I.
Specific embodiment
For the ease of a further understanding of the present invention, examples provided below has done more detailed description to it.But
It is that these embodiments are only not supposed to be a limitation to the present invention or implementation principle for better understanding invention, reality of the invention
The mode of applying is not limited to the following contents.
Embodiment 1
(1) dry uncaria buckle stem branch (100g) is taken to be crushed to 20-100 mesh, with 95% ethyl alcohol (800mL) refluxing extraction
After 10 hours, filtering, filtrate are concentrated to give extract；
(2) for the extract that step (1) obtains first through silica gel column chromatography, stationary phase is 200-300 mesh silica gel, and mobile phase uses
Petroleum ether-ethyl acetate press 100:0,90:10,80:20,70:30,60:40,50:50,40:60,30:70,20:80,10:90,
0:100 gradient elution, each gradient collect 3 column volumes, and the fraction that wherein 90:10 and 80:20 gradient elution obtains merges dense
Prepare that (chromatographic condition: chromatographic column is Agilent Eclipse XDB-C18,9.4 × 250mm, 5 μ after contracting through high performance liquid chromatography
M, flow velocity 1.5mL/min, mobile phase MeOH:H2O=60:40 white solid (38mg)) is obtained, the as described Formulas I structure
Uncaria indoles diterpene alkaloid.
1H NMR(CDCl3,600MHz)δ:7.78(1H,s,NH-1),7.46-7.44(1H,m,H-20),7.33-7.30
(1H, m, H-23), 7.12-7.10 (2H, m, H-21,22), 3.26-3.22 (1H, dd, J=12.0,2.4Hz, H-9), 3.08-
3.04 (1H, dd, J=12.0,3.6Hz, H-7), 2.82-2.75 (1H, m, H-16), 2.72-2.68 (1H, dd, J=13.3,
6.6Hz, Ha-17), 2.38-2.33 (1H, dd, J=13.3,10.9Hz, Hb-17), 2.02-1.95 (1H, m, Ha-5), 1.87-
1.77(2H,m,Hb-11,Ha-15),1.72-1.60(4H,m,Ha-14,Ha-10,Hb-5,Hb-15),1.52-1.39(3H,m,
H-13,Hb-14,Hb-10),1.22(3H,s,CH3-29),1.21(3H,s,CH3-28),1.16(3H,s,CH3-26),1.15-
1.14(1H,m,Ha-11),1.05(3H,s,CH3-25),0.91(3H,s,CH3-30)；13C NMR(CDCl3,125MHz)δ:
150.8,140.0,125.1,120.4,119.5,118.4,118.2,111.4,85.7,84.7,72.0,53.0,48.8,
46.4,40.0,37.7,36.6,33.9,26.1,25.3,24.6,23.7,22.0,21.9,20.0,14.6,12.7；ESIMS
m/z[M+H]+422.61,[M+H]+444.60.
Embodiment 2
The cytotoxic activity of hepatoma H22 cells is tested in this experiment according to mtt assay.It is thin with pancreatin digestion logarithmic phase first
Cell is uniformly diluted and is made 2 × 10 by born of the same parents4The single cell suspension of a/mL is inoculated in 96 orifice plates and 100 μ L is respectively added, then puts
Enter constant temperature incubation in cell incubator (37 DEG C of constant temperature, 5%CO2Under the conditions of cultivate), for 24 hours after it is adherent to cell, be added Formulas I
Compound makes final compound concentration be followed successively by 0.625 μ g/mL, 1.25 μ g/mL, 2.5 μ g/mL, 5 μ g/mL, 25 μ g/mL, and sets
Blank control wells and each three of Positive control wells (positive control drug cis-platinum) are set, is used after 48h and uses automatic elisa plate reader
Measure absorbance of each hole at 490nm.In triplicate, compared with negative control, compound on tumor cell is calculated separately
Inhibiting rate and IC50Value.The result shows that the IC of formula Compound I50Value is 14.2 ± 2.1 μ g/mL.
Claims (10)
1. a kind of uncaria indoles diterpene alkaloid or its pharmaceutically acceptable salt, it is characterised in that the uncaria indoles diterpene is raw
Alkaloids have structure shown in Formulas I:
2. the preparation method of uncaria indoles diterpene alkaloid described in claim 1, it is characterised in that include the following steps:
(1) dry uncaria buckle stem branch is crushed, after being extracted 10-12 hours with 95% alcohol reflux, filtering, filtrate are concentrated to give
Extract；
(2) extract that step (1) obtains is through chromatographic isolation up to the uncaria indoles diterpene alkaloid.
3. preparation method as claimed in claim 2, it is characterised in that the preferred 20-100 mesh of crushing described in step (1), every kilogram
It is preferable to use the preferred 8-10L of the dosage of 95% ethyl alcohol for dry uncaria buckle stem branch.
4. the described in any item preparation methods of claim 2-3, it is characterised in that the preferred silicagel column of step (2) chromatographic isolation
Chromatography is combined with high performance liquid chromatography preparation；Specially for extract first through silica gel column chromatography, stationary phase is 200-300 mesh silica gel,
Mobile phase using petroleum ether-ethyl acetate press 100:0,90:10,80:20,70:30,60:40,50:50,40:60,30:70,
20:80,10:90,0:100 gradient elution, each gradient collect 3 column volumes, and wherein 90:10 and 80:20 gradient elution obtains
Fraction merge concentration after through high performance liquid chromatography be prepared into the uncaria indoles diterpene alkaloid.
5. preparation method as claimed in claim 4, it is characterised in that the chromatographic condition that the high performance liquid chromatography preparation uses: color
Composing column is Agilent Eclipse XDB-C18,9.4 × 250mm, 5 μm, flow velocity 1.5mL/min, mobile phase MeOH:H2O
=60:40.
6. application of the uncaria buckle stem branch in the uncaria indoles diterpene alkaloid described in preparation claim 1.
7. uncaria indoles diterpene alkaloid described in claim 1 or its pharmaceutically acceptable salt are in the preparation of antitumor drugs
Application.
8. a kind of pharmaceutical composition, it is characterised in that described pharmaceutical composition is raw with uncaria indoles diterpene described in claim 1
Alkaloids or its pharmaceutically acceptable salt are as effective component.
9. pharmaceutical composition according to any one of claims 8, it is characterised in that the pharmaceutical composition may also include other anti-tumor drugs.
10. the described in any item pharmaceutical compositions of claim 8-9, it is characterised in that the pharmaceutical composition may also include pharmaceutically
The auxiliary material that can be connect.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910508550.7A CN110105422B (en) | 2019-06-12 | 2019-06-12 | Uncaria indole diterpenoid alkaloid and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910508550.7A CN110105422B (en) | 2019-06-12 | 2019-06-12 | Uncaria indole diterpenoid alkaloid and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110105422A true CN110105422A (en) | 2019-08-09 |
| CN110105422B CN110105422B (en) | 2020-03-27 |
Family
ID=67494859
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910508550.7A Active CN110105422B (en) | 2019-06-12 | 2019-06-12 | Uncaria indole diterpenoid alkaloid and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110105422B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113717190A (en) * | 2021-10-08 | 2021-11-30 | 中国科学院昆明植物研究所 | Indole alkaloid, pharmaceutical composition thereof, preparation method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5541208A (en) * | 1994-01-24 | 1996-07-30 | Merck & Co., Inc. | Indole diterpene alkaloid compounds |
| US6548535B2 (en) * | 2000-01-18 | 2003-04-15 | Merck & Co., Inc. | Method for treating ocular hypertension |
| WO2003105868A1 (en) * | 2002-06-17 | 2003-12-24 | Merck & Co., Inc. | Novel maxi-k channel blockers, methods of use and process for making the same |
| CN102311436A (en) * | 2011-07-05 | 2012-01-11 | 南京泽朗农业发展有限公司 | Preparation method of isorhynchophylline |
-
2019
- 2019-06-12 CN CN201910508550.7A patent/CN110105422B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5541208A (en) * | 1994-01-24 | 1996-07-30 | Merck & Co., Inc. | Indole diterpene alkaloid compounds |
| US6548535B2 (en) * | 2000-01-18 | 2003-04-15 | Merck & Co., Inc. | Method for treating ocular hypertension |
| WO2003105868A1 (en) * | 2002-06-17 | 2003-12-24 | Merck & Co., Inc. | Novel maxi-k channel blockers, methods of use and process for making the same |
| CN102311436A (en) * | 2011-07-05 | 2012-01-11 | 南京泽朗农业发展有限公司 | Preparation method of isorhynchophylline |
Non-Patent Citations (1)
| Title |
|---|
| NA GAO ET AL.: "Alkaloids from the endophytic fungus Penicillium brefeldianum and their cytotoxic activities", 《CHINESE CHEMICAL LETTERS》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113717190A (en) * | 2021-10-08 | 2021-11-30 | 中国科学院昆明植物研究所 | Indole alkaloid, pharmaceutical composition thereof, preparation method and application thereof |
| CN113717190B (en) * | 2021-10-08 | 2023-06-13 | 中国科学院昆明植物研究所 | Indole alkaloid and pharmaceutical composition thereof, and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110105422B (en) | 2020-03-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105732381B (en) | Antrodia camphorata extract and preparation method and application thereof | |
| CN112266377A (en) | Dendrobium officinale Kimura et Migo extract analogue and preparation method and application thereof | |
| US20130324580A1 (en) | Anti-Cancer Agents Synthesized Based On Miliusane Compounds | |
| CN101240005A (en) | Method for preparing platycodin D from balloon-flower root and application thereof in anti-cancer medicament | |
| CN110105422A (en) | A kind of uncaria indoles diterpene alkaloid and the preparation method and application thereof | |
| Panthama et al. | Chemical constituents from the fungus Chaetomium cupreum RY202 | |
| US10493056B2 (en) | Method of use of diterpenoid derivatives as anticancer agents | |
| CN110642919B (en) | Terpenoid with indole ring, pharmaceutical composition, preparation method and application thereof | |
| CN113004297A (en) | Diterpene alkaloid compound and extraction method and application thereof | |
| CN110105421A (en) | A kind of oxidation uncaria indoles diterpene alkaloid and the preparation method and application thereof | |
| CN113214214B (en) | Preparation method and application of terpenoid in Atractylodes lancea | |
| CN104804057B (en) | Pregnane alkaloid and preparation method thereof and the purposes in antineoplastic is prepared | |
| CN113024498B (en) | Ficus-japonica alkane sesterterpene compound, preparation method thereof, pharmaceutical composition and application thereof, and application of total extract of Ficus-japonica | |
| CN108912091A (en) | A kind of HERBA DENDROBII bibenzyl based component and extract separation and chiral separation method | |
| CN108836982A (en) | A kind of toad skin active component and preparation method thereof | |
| CN109053641A (en) | Two Ne olignans of one kind and method for separating and preparing and application | |
| CN110143992A (en) | Ergosterol class compound with anti-inflammatory activity and its preparation method and application | |
| CN105669692B (en) | A kind of extracting method and purposes of phthalide-type dimer compound | |
| CN108129541A (en) | A kind of triterpene compound and its methods and applications extracted from ganoderma lucidum | |
| CN112047887B (en) | Tinospora sinensis amide and preparation method and application thereof | |
| CN106966969B (en) | A kind of alkaloid compound and its preparation method and application | |
| CN115073481B (en) | Furana quebracho base dimer or pharmaceutically acceptable salt thereof, and preparation method and application thereof, and pharmaceutical composition | |
| CN106495998A (en) | A kind of bibenzyl ether compound and preparation method thereof and purposes | |
| CN111217824B (en) | 4-O-arylaminopropyl glycyrrhiza A derivative and preparation and application thereof | |
| CN105294815B (en) | A kind of compound and its preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |