CN106317157B - A kind of polyhydroxy diketone class cucurbit alkane type triterpenoid and its preparation method and purposes - Google Patents
A kind of polyhydroxy diketone class cucurbit alkane type triterpenoid and its preparation method and purposes Download PDFInfo
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Abstract
The invention discloses a kind of polyhydroxy diketone class cucurbit alkane type triterpenoid isolated and purified from Jinfo Shan Mountain hymsleya amabilis rhizome and its preparation methods and purposes, and its chemical structure and physicochemical property has been determined using modern analysis means, according to there is the naming rule of related compounds to be named as 2β,3α,7β,16α,20β, -5 (E)-monoene -11,22- diketone of 25- hexahydroxy cucurbitane terpene, be colourless powder, be soluble in chloroform, methanol, the compound be a noval chemical compound.It is proved through functional trial: 2β,3α,7β,16α,20β, -5 (E)-monoene -11,22- diketone of 25- hexahydroxy cucurbitane terpene has stronger inhibiting effect to the tumour cells such as HeLa cell and KB cell, can have stronger application value and market prospects as the raw material of preparation prevention and treatment tumour medicine.
Description
Technical field
The present invention relates to a kind of polyhydroxy diketone class cucurbitane type tetraterpene derivatives and its preparation methods and purposes, refer specifically to 2β,
3α, 7β, 16α, 20β, -5 (E)-monoene -11,22- diketone of 25- hexahydroxy cucurbitane terpene and its preparation method and purposes.
Background technique
Jinfo Shan Mountain hymsleya amabilis (Hemsleya pengxianensis W. J. Chang var. jinfushanensis L.
D. Shen W. J. Chang) it is Curcurbitaceae (Fabaceae) hymsleya amabilis platymiscium, China region of Southeast is originated in, sea is born in
It pulls out in 2000 meters or so of border and mountain valley shrubbery.The fruit of Jinfo Shan Mountain hymsleya amabilis is in 4-5 centimetres oval, long, and 2.5-3.5 lis of diameter
There is tiny verruca on rice, pericarp surface and distinguishes with former mutation, and main active is respectively cucurbitane type Fourth Ring three
Terpene and its saponin(e and Triterpenoids sapogenins and its saponin(e have clearing heat and detoxicating, the multiple efficacies such as antibacterial anti-inflammatory, clinically
It is mainly used for treating a variety of diseases such as bacillary dysentery, various inflammation, ulcer, jaundice.
The drug effect of Jinfo Shan Mountain hymsleya amabilis is mainly derived from cucurbitane type triterpene compound therein, therefore, develops and utilizes
Cucurbitane type monomeric compound in hymsleya amabilis, further excavates its potential medical value, and to the knot of monomer compound
Structure and physicochemical property are determined and characterize, and are of great significance for development and utilization Jinfo Shan Mountain hymsleya amabilis resource.
Summary of the invention
The present invention is exactly to overcome the deficiencies of the prior art and provide a kind of isolated from Jinfo Shan Mountain hymsleya amabilis rhizome to have
The polyhydroxy diketone class Cucurbitanes of important biomolecule activity and industrialization utility value.The monomeric compound is from golden Buddhist
It is isolated for the first time in the hymsleya amabilis of mountain, after characterizing its structure using modern analysis means and confirm its bioactivity, according to relatedization
The naming rule for closing object is named as 2β, 3α, 7β, 16α, 20β, -5 (E)-monoene -11,22- of 25- hexahydroxy cucurbitane terpene
Diketone, the compound are a noval chemical compound.
A kind of isolated from Jinfo Shan Mountain hymsleya amabilis rhizome 2β, 3α, 7β, 16α, 20β, 25- hexahydroxy cucurbitane
Terpene -5 (E)-monoene -11,22- diketone has the structure that is shown below:
Above-mentioned isolated from Jinfo Shan Mountain hymsleya amabilis rhizome 2β, 3α, 7β, 16α, 20β, 25- hexahydroxy cucurbit
Alkane terpene -5 (E)-monoene -11,22- diketone obtains as follows:
The sieving of Jinfo Shan Mountain hymsleya amabilis rhizome crushed after being dried, adds 95% ethyl alcohol heating and refluxing extraction 3 times, 1-3 hours each, closes
And extracting solution, solvent is recovered under reduced pressure, total medicinal extract is obtained after concentration, after total medicinal extract is water-dispersible, successively uses petroleum ether, chloroform, acetic acid
Ethyl ester, extracting n-butyl alcohol, extract liquor are concentrated to dryness；Ethyl acetate extract medicinal extract is taken to be separated with silica gel column chromatography, chloroform-methanol
(1:0-0:1) gradient elution obtains 12 parts fraction Fr A-L, Fr.F and is made again with chloroform-methanol after gel chromatography elutes
Depigmentaton is removed for elution, then the inverted middle pressure chromatographic column of sample is through MeOH-H2O (60:40; 70:30; 80:20;
90:10) gradient elution obtains four part Fr. F1-4, and wherein Fr. F3 is separated through high-efficient liquid phase chromatogram purification, using first
Alcohol-water elution, the eluent collected 16.7 minutes crystallize to obtain the final product.
The mass volume ratio of Jinfo Shan Mountain hymsleya amabilis rhizome and ethyl alcohol is 1:8-1:12 in the heating and refluxing extraction.
The volume ratio of chloroform and methanol is 45:55-60:40 in the chloroform-methanol eluent.
The volume ratio of methanol and water is 80:20 in the methanol-water eluent.
2β, 3α, 7β, 16α, 20β, -5 (E)-monoene -11,22- diketone of 25- hexahydroxy cucurbitane terpene is no toner
End is soluble in chloroform, methanol, by 2β, 3α, 7β, 16α, 20β, -5 (E)-monoene -11 of 25- hexahydroxy cucurbitane terpene,
22- diketone carries out extracorporeal anti-tumor pharmacodynamic experiment, and extracorporeal anti-tumor pharmacodynamic experiment utilizes MTT colorimetric method.
With 2β, 3α, 7β, 16α, 20β, -5 (E)-monoene -11,22- diketone of 25- hexahydroxy cucurbitane terpene is experiment
Group, with Doxorubicin(Doxorubicin, anti-tumor drug) be control group, while setting up blank group, experimental group, control group and
Blank group chooses HeLa(human cervical carcinoma) cell and KB(human mouth epidermoid carcinoma) it is experimental subjects, after culture medium dilution, with 6 ×
The density of 104/ml is inoculated in 96 orifice plates, every 100 μ l of hole, and after normally cultivating 24 hours in incubator, each group is added corresponding
Drug, making the ultimate density of each group drug is respectively 2.5 μ g/ml (1 group), 5 μ g/ml (2 groups), 10 μ g/ml (3 groups),
20 μ g/ml (four groups), 40 μ g/ml (5 groups) set 5 concentration, 3 multiple holes of each concentration altogether；After culture 48 hours, in every
Hole adds 10 μ l of MTT to dye；It after continuing culture four hours, inhales and abandons original fluid, every hole is added 100 μ l of DMSO, sets low on shaking table
Speed 10 min of oscillation, dissolve crystal sufficiently, and detect OD value, root at 570 nm wavelength of enzyme-linked immunosorbent assay instrument
50% inhibition concentration (IC is calculated according to OD value50, μ g/mL), OD value calculates IC50Calculation method be existing known skill
Art.Experimental group, control group are to the IC of HeLa cell and KB cell50As shown in table 1.
Table 1
| Group | HeLa cell | KB cell |
| Experimental group | 2.9 ± 0.8 | 14.7 ± 1.6 |
| Control group | 1.3 ± 0.11 | 0.89 ± 0.03 |
It can be seen that of the present invention 2 by the data of upper tableβ, 3α, 7β, 16α, 20β, 25- hexahydroxy calabash
- 5 (E)-monoene -11,22- diketone of reed alkane terpene all has certain inhibiting effect to HeLa cell and KB cell, can be as system
The raw material of standby prevention and treatment tumour medicine has stronger industrial application value.
Compared with prior art, the beneficial effects of the present invention are:
Isolated 2 with important anti-tumor activity from Jinfo Shan Mountain hymsleya amabilis rhizome for the first timeβ, 3α, 7β, 16α,
20β, -5 (E)-monoene -11,22- diketone of 25- hexahydroxy cucurbitane terpene, and it has been determined that its chemistry is tied using modern analysis means
Structure and physicochemical property.It is proved through functional trial: 2β, 3α, 7β, 16α, 20β, 25- hexahydroxy cucurbitane terpene -5 (E)-mono-
Alkene -11,22- diketone has stronger inhibiting effect to tumour cell, can be as the raw material of preparation prevention and treatment tumour medicine, tool
There are stronger application value and market prospects.
Detailed description of the invention
Fig. 1 is 2β, 3α, 7β, 16α, 20β, -5 (E)-monoene -11,22- diketone of 25- hexahydroxy cucurbitane terpene
Schematic arrangement.
Fig. 2 is 2β, 3α, 7β, 16α, 20β, -5 (E)-monoene -11,22- diketone of 25- hexahydroxy cucurbitane terpene
Nuclear magnetic resonance spectroscopy (1H-NMR).
Fig. 3 is 2β, 3α, 7β, 16α, 20β, -5 (E)-monoene -11,22- diketone of 25- hexahydroxy cucurbitane terpene
Carbon-13 nmr spectra (13C-APT).
Specific embodiment
Below in conjunction with specific embodiment, the present invention is further illustrated
Step 1: Jinfo Shan Mountain hymsleya amabilis rhizome (5.0 kg) crushed after being dried crosses 80 meshes.Step 2: medicinal powder adds 10 times
Amount ethyl alcohol heating and refluxing extraction 3 times, 2 hours every time, solvent was recovered under reduced pressure in combined extract, and total 1033 g of medicinal extract is obtained after concentration.
Step 3: the total medicinal extract of Jinfo Shan Mountain hymsleya amabilis rhizome add suitable quantity of water carry out decentralized processing after, respectively with petroleum ether, chloroform, ethyl acetate,
N-butanol is extracted, and is extracted to colourless, and extract liquor is concentrated to dryness, the total medicinal extract 56g of petroleum ether part, chloroform are weighed to obtain
The total medicinal extract 302g in position, the total medicinal extract 151g of ethyl acetate extract, total 409 g of medicinal extract of n-butanol portion.Step 4: taking ethyl acetate
Layer 151 g of medicinal extract is separated through silica gel column chromatography (100~200 mesh), and chloroform-methanol (1:0-0:1) gradient elution obtains 12 and evaporates
Divide Fr A-L.Step 5: the part Fr.F is eluted through gel chromatography, chloroform-methanol (45:55) removes discoloration as elution
Element, then the inverted middle pressure chromatographic column of sample is through MeOH-H2O (60:40; 70:30; 80:20;90:10) gradient elution obtains
To four part Fr. F1-4. step 6: wherein Fr. F3 is separated through high-efficient liquid phase chromatogram purification, using methanol-water (80:
20) it elutes, the eluent crystallization collected 16.7 minutes obtains colourless powder, is soluble in chloroform, methanol.
The structural characterization of above-mentioned colourless powder and confirmation are as follows:
By above-mentioned gained colourless powder carry out nuclear magnetic resonance spectroscopy (1H-NMR) and carbon-13 nmr spectra (13C-APT it) analyzes
,1H-NMR spectrum as shown in Fig. 2,13C-APT spectrogram is as shown in Figure 3.
Spectrum analysis is carried out to Fig. 2 and Fig. 3, each peak Fig. 2 and Fig. 3 is belonged to, the peak of Fig. 2 and Fig. 3 belong to such as 2 institute of table
Show, by the data of Fig. 2, Fig. 3 and table 1 it is found that the chemical structural formula of colourless powder is as shown in Figure 1, according to there are related compounds
Naming rule be named as 2β, 3α, 7β, 16α, 20β, -5 (E)-monoene -11,22- two of 25- hexahydroxy cucurbitane terpene
Ketone.
English entitled 2β, 3α, 7β, 16α, 20β, 25-hexahydroxycucurbita-5(E)-ene-11,
22-dione。
2 compound 1 of table1H-NMR and13C-NMR (150MHz, C5D5N) modal data
Above-mentioned only presently preferred embodiments of the present invention, is not intended to limit the present invention in any form.It is any to be familiar with sheet
The technical staff in field, without deviating from the scope of the technical scheme of the present invention, all using the technology contents of the disclosure above
Many possible changes and modifications or equivalent example modified to equivalent change are made to technical solution of the present invention.Therefore, all
It is the content without departing from technical solution of the present invention, technical spirit is made to the above embodiment according to the present invention any simply repairs
Change, equivalent variations and modification, all shall fall within the protection scope of the technical scheme of the invention.
Claims (5)
1. a kind of compound is preparing the application in anti-oral cavity epidermoid carcinoma KB cell drug, it is characterised in that: the compound is
Colourless powder is soluble in chloroform, methanol, and has structure as follows
。
2. a kind of preparation method of compound described in claim 1, it is characterised in that: Jinfo Shan Mountain hymsleya amabilis rhizome crushed after being dried mistake
Sieve, adds 95% ethyl alcohol heating and refluxing extraction 3 times, and 1-3 hours each, solvent is recovered under reduced pressure in combined extract, obtains after concentration and always soaks
Cream after total medicinal extract is water-dispersible, successively uses petroleum ether, chloroform, ethyl acetate, extracting n-butyl alcohol, and extract liquor is concentrated to dryness；Take second
Acetoacetic ester position medicinal extract is separated with silica gel column chromatography, chloroform-methanol 1:0-0:1 gradient elution, obtains 12 fraction Fr A-L,
Fr.F after gel chromatography elutes uses chloroform-methanol to remove depigmentaton as elution in part again, then sample it is inverted in
Press chromatographic column through MeOH-H2O is with 60:40; 70:30; 80:20;90:10 carries out gradient elution, obtains four part Fr.
F1-4, wherein Fr. F3 is separated through high-efficient liquid phase chromatogram purification, is eluted using methanol-water, and 16.7 minutes eluent knots are collected
Crystalline substance to obtain the final product.
3. the preparation method of compound according to claim 2: it is characterized by: Jinfo Shan Mountain is avenged in the heating and refluxing extraction
The mass volume ratio of gallbladder rhizome and ethyl alcohol is 1:8-1:12.
4. the preparation method of compound according to claim 2: it is characterized by: in gel chromatography elution, chloroform-first
The volume ratio of chloroform and methanol is 45:55-60:40 in alcohol eluen.
5. the preparation method of compound according to claim 2: it is characterized by: the high-efficient liquid phase chromatogram purification separates
In, the volume ratio of methanol and water is 80:20 in methanol-water eluent.
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| CN115160396B (en) * | 2022-08-03 | 2024-04-05 | 河南中医药大学 | Cucurbitane-type tetracyclic triterpene compound with anti-enteritis activity extracted from Chinese hemsleya root, and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103665082A (en) * | 2013-12-10 | 2014-03-26 | 山东省医学科学院药物研究所 | Hemsleya cucurbitane tetracyclic triterpenoid compound, pharmaceutical compositions containing same and application of compound and pharmaceutical composition |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103665082A (en) * | 2013-12-10 | 2014-03-26 | 山东省医学科学院药物研究所 | Hemsleya cucurbitane tetracyclic triterpenoid compound, pharmaceutical compositions containing same and application of compound and pharmaceutical composition |
Non-Patent Citations (1)
| Title |
|---|
| Cytotoxic cucurbitane triterpenoids isolated from the rhizomes of Hemsleya amabilis;Xu-Bing Chen et al.;《Fitoterapia》;20140124;第94卷;第91页图1，第92页表3，第89页 * |
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