CN105732379B - A kind of diphenyl heptane compound and its preparation method and application - Google Patents
A kind of diphenyl heptane compound and its preparation method and application Download PDFInfo
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Abstract
The invention belongs to pharmaceutical technology field, a kind of diphenyl heptane compound and preparation method thereof and the application in preparation treatment psoriasis or food are disclosed.Biologically active diphenyl heptane compound of the invention has the structure as shown in following formula I:
Description
Technical field
The invention belongs to pharmaceutical technology field, in particular to a kind of diphenyl heptane compound and preparation method thereof and preparing
Treat the application in psoriasis or food.
Background technique
Guangxi zedoary is the dry rhizome of Zingiber curcuma, is one of common traditional Chinese medicine.Version China in 2005
Pharmacopeia is recorded: curcuma zedoary is zingiberaceous plant zedoary (Curcuma phaeocaulis Valeton), Guangxi zedoary (Curcuma
Kwangsiensis S.G.Lee et C.F.Liang) or RADIX CURCUMAE (Curcuma wenyuj in Y.H.Chen et
C.Ling dry rhizome) mainly originates in the places such as Guangxi, Sichuan, Zhejiang, Fujian.Traditional Chinese medicine and pharmacy theory thinks, property is pungent,
Bitter, temperature, has the effect of promoting the circulation of qi blood-breaking, clearing stagnation and killing pain.Cure mainly pained vim and vigour, eating accumulation, abdominal distention, amenorrhea due to stagnation of blood, pain
Through, traumatic injury.Two major classes active constituent, i.e. compound in diphenyl heptane class and volatile oil are typically contained in curcuma
Object is closed, in addition to this, also containing ingredients such as Diterpenes, polysaccharide, phenolic acid class and sterols.Have been demonstrated that diphenyl heptane class chemical combination
Object and volatile oil component are its primary bioactive components.Domestic and foreign scholars confirm diphenyl heptane class by pharmacological experiment
Compound has a variety of biologies such as antiemetic, treating tuberculosis, liver protection, anticoccidial, antimycotic, anticancer and inhibition prostaglandin synthesis living
Property.
Psoriasis is one of dermatology common disease, frequently-occurring disease, and it is always that puzzlement is complete that the cause of disease is complicated and recurrent exerbation
The difficult medical problem of ball.Its histopathology feature is mainly shown as epidermal keratinocytes cellulation abnormality proliferation and differentiation, and with skin
The infiltration of skin inflammatory cell.Currently, mainly there are four aspects for the method for the western medical treatment disease: externally applied drug treatment, as steroids swashs
Element, tacrolimus and vitamin D 3-derivatives etc.；Systemic drug treatment, such as tretinoin medicines, methotrexate (MTX) and cyclosporine
Deng；Physical therapy, such as narrow-band UVB irradiation treatment；Biological agent, such as Etanercept, Ah method's Saite and in accordance with the law sharp pearl is single
It is anti-etc..But the problem of all unavoidable pharmacological dependence of these therapies and recurrence, simultaneity factor drug bring biggish secondary work again
With, and biological agent is expensive, these all limit the clinical application of these therapies.Psoriasis Treated by TCM method is more
Sample, administration is flexible and changeable, and curative effect is preferable, and Small side effects, and has both cheap advantage, in terms of clinical treatment psoriasis
It receives significant attention.But Chinese medicine compound prescription ingredient is indefinite, and its qualitative and safety evaluation method is incomplete, limits
Its clinical expansion and application.Therefore, traditional Chinese medicine monomer curative for effect is isolated from Chinese medicine, is Psoriasis Treated by TCM from now on
Main direction of studying.
Summary of the invention
In order to overcome the shortcomings and deficiencies of the prior art described above, the primary purpose of the present invention is that providing a kind of with biology
Active diphenyl heptane compound.
Another object of the present invention is to provide a kind of preparation method of above-mentioned biologically active diphenyl heptane compound.
Still a further object of the present invention is that providing above-mentioned biologically active diphenyl heptane compound treats silver bits in preparation
Application in medicine or food.
The purpose of the present invention is realized by following proposal:
A kind of biologically active diphenyl heptane compound has the structure as shown in following formula I:
The chemical name of the biologically active diphenyl heptane compound is two (4- of (E) -3- acetoxyl group -1,7-
Hydroxy phenyl) -6- heptene.
Biologically active diphenyl heptane compound of the invention can be prepared from plant extract or synthetic method.
The synthetic method refers to can synthesize to obtain with the compound analog.
The present invention also provides a kind of preparation method of above-mentioned biologically active diphenyl heptane compound, including it is as follows
Specific steps:
(1) curcuma zedoary rhizome is taken, is extracted with 95v/v% alcohol-water, extract is through HP-20 large pore resin absorption column chromatography point
From successively with water, 30v/v% ethyl alcohol, 90~100v/v% ethanol gradient elution collects eluent respectively, is concentrated under reduced pressure, obtains
Water elution position, 30v/v% alcohol elution, 90~100v/v% alcohol elution；
(2) 90~100v/v% alcohol elution for taking step (1), separates through silica gel column chromatography, with chloroform-methanol ladder
The fraction that chloroform-methanol ratio is 9:1 is collected in degree elution, collects first with methanol-water gradient elution through ODS pillar layer separation
Alcohol-water ratio is the fraction of 7:3, separates through preparative liquid chromatography HPLC, obtains biologically active diphenyl heptane compound.
In above-mentioned preparation method, step (2) described preparative liquid chromatography, using ratio for 65:35 methanol-water as flowing
Phase, Detection wavelength are 208nm and 220nm, flow velocity 12mL/min, biologically active diphenyl heptane compound of the invention
Retention time in preparation liquid phase is 20.3min.
The biologically active diphenyl heptane compound of aforementioned present invention, which has, inhibits human T cell lymphoma cell line HH
The bioactivity of cell Proliferation can be applied in preparation prevention and treatment psoriasis or food.
Described is applied to have in preparation prevention and treatment psoriasis or food middle finger drug or food containing of the invention
The diphenyl heptane compound ((E) -3- acetoxyl group -1,7- two (4- hydroxy phenyl) -6- heptene) of bioactivity, its pharmaceutical salts and
At least one of solvate.Well known, the solvation form and salt of compound usually have no effect on the life of combound itself
Object activity.
The drug contains one or more pharmaceutically acceptable carriers or excipient.
The present invention have the following advantages compared with the existing technology and the utility model has the advantages that
Present invention separation and Extraction from Guangxi zedoary rhizome obtains a kind of new diphenyl heptane compound, (E) -3- acetyl oxygen
Base -1,7- bis- (4- hydroxy phenyl) -6- heptene, by the testing in vitro to human T cell lymphoma cell line HH cell Proliferation, really
Fixed its is prevented and treated psoriasis or food with preferable Inhibit proliferaton effect, and in dose-effect relationship, thus suitable for preparation.
Detailed description of the invention
Fig. 1 is diphenyl heptane compound of the present invention to human T cell lymphoma cell line HH cell inhibitory effect effect picture.
Specific embodiment
Below with reference to embodiment and attached drawing, the present invention is described in further detail, but embodiments of the present invention are unlimited
In this.
Fetal calf serum (FBS) is purchased from Hyclone company；RPMI1640 culture medium, human T cell lymphoma cell line HH cell
Purchased from ATCC company；CCK-8 cytoactive detection kit is purchased from eastern Renhua subject skill (Shanghai) Co., Ltd..
Embodiment 1: the separation and Extraction of diphenyl heptane compound of the invention
Dry Guangxi zedoary rhizome is taken, is extracted with 95v/v% alcohol-water, extract is through HP-20 large pore resin absorption column color
Spectrum separation collects each eluent successively with water, 30v/v% ethyl alcohol, 90~100v/v% ethanol gradient elution respectively, depressurizes dense
Contracting, obtains water elution position, 30v/v% alcohol elution, 90~100v/v% alcohol elution；Take 90~100v/v%
Alcohol elution is separated through silica gel column chromatography, and with chloroform-methanol gradient elution, collecting chloroform-methanol ratio is evaporating for 9:1
E, fraction E is divided to collect the fraction E-6 that methanol-water ratio is 6:4, fraction with methanol-water gradient elution through ODS pillar layer separation
E-6 obtains the compounds of this invention through preparation liquid phase HPLC separation.
In above-mentioned preparation method, step (2) described preparative liquid chromatography, using ratio for 65:35 methanol-water as flowing
Phase, Detection wavelength are 208 and 220nm, flow velocity 12mL/min, and the retention time in preparation liquid phase is 20.3min, separate institute
It is dry to obtain solution, obtains the compounds of this invention 57.4mg.
Embodiment 2: the structural identification of the compounds of this invention
The compound that the present invention obtains is yellow oil.Negative source HR-ESI-LTQ/Orbitrap-MS shows m/z [M-
H]-339.1584 high resolution mass spectrum provides molecular formula C21H24O4。
1H-NMR data, chemical shift (multiplicity, coupling constant) when 500MHz, coupling constant unit are Hz:2.52
(2H,m,H-1),1.82(2H,m,H-2),4.93(1H,m,H-3),1.70(2H,m,H-4),2.16(2H,m,H-5),5.98
(1H,dt,16.0,7.5,H-6),6.25(1H,d,16.0,H-7),6.97(4H,d,8.5,H-2’,6’),6.68(4H,d,
8.5,H-3’,5’),7.15(4H,d,8.5,H-2”,6”),6.69(4H,d,8.5,H-3”,5”),2.00(3H,s,CH3)。
13C-NMR data, chemical shift when 125MHz: 32.1 (C-1), 37.6 (C-2), 75.2 (C-3), 35.4 (C-4),
30.3(C-5),127.7(C-6),131.6(C-7),131.0(C-1’),128.5(C-2’,6’),116.5(C-3’,5’),
157.9 (C-4 '), 133.9 (C-1 "), 130.6 (C-2 ", 6 "), 116.4 (C-3 ", 5 "), 156.7 (C-4 "), 173.2 (C=
O),21.5(CH3)。
By MS,1H-NMR and13It is (E) -3- acetoxyl group -1,7- two (4- hydroxy phenyl) -6- heptan that C-NMR, which confirms structure,
Alkene.
Embodiment 3: the external anti-human T cell's lymphoma cell line HH cell Proliferation detection of the compounds of this invention
1600rpm, 3min are collected by centrifugation the human T cell lymphoma cell line HH cell in logarithmic growth phase, and with containing
1640 culture mediums of 10%FBS are resuspended；The HH cell suspension of 100 μ L is added in every hole in 96 orifice plates, until final concentration of 2 × 104
A cell per well.The isolated compound of embodiment 1 is dissolved in DMSO, is configured to the storing liquid of final concentration of 10mM；In use,
The storing liquid of 10 μ L is taken to be added in the RPMI1640 culture medium of 90 μ L, be diluted to 1mM uses liquid；Meanwhile taking 10 μ L's
DMSO, which is added in the RPMI1640 culture medium of 90 μ L, uses liquid as negative control group.Take 0 respectively, 1,2,2.5,3,3.5,5,
0,10,20,25,30,35,50,100 μM of concentration gradient is made in being added using liquid into 96 orifice plates of 10 μ L；Meanwhile it is negative right
Liquid is used according to a group negative control group for addition respective volume.37 DEG C, 5%CO2It is cultivated in incubator for 24 hours, every hole is added 10 μ L's
CCK-8 is protected from light culture 4h in incubator, and using the light absorption value of microplate reader measurement 450nm, convert inhibiting rate, uses Graphpad
Software mapping, the result is shown in Figure 1.
Inhibiting rate %=[1- (experimental group OD/ control group OD)] × 100%
As seen from Figure 1, it by using CCK-8 kit measurement cell viability, finds compared with negative control group, through this hair
After bright compound processing, HH cell Proliferation receives obvious inhibition.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention,
It should be equivalent substitute mode, be included within the scope of the present invention.
Claims (2)
1. a kind of preparation method of biologically active diphenyl heptane compound, it is characterised in that comprise the following specific steps that:
(1) take curcuma zedoary rhizome, extracted with 95v/v% alcohol-water, extract through HP-20 large pore resin absorption column chromatographic isolation, according to
Secondary with water, 30v/v% ethyl alcohol, 90~100v/v% ethanol gradient elution collects eluent respectively, is concentrated under reduced pressure, is washed
De- position, 30v/v% alcohol elution, 90~100v/v% alcohol elution；
(2) 90~100v/v% alcohol elution for taking step (1), separates through silica gel column chromatography, is washed with chloroform-methanol gradient
It is de-, the fraction that chloroform-methanol ratio is 9:1 is collected, collects methanol-water with methanol-water gradient elution through ODS pillar layer separation
Ratio is the fraction of 7:3, separates through preparative liquid chromatography HPLC, obtains biologically active diphenyl heptane compound；
The biologically active diphenyl heptane compound has the structure as shown in following formula I:
2. the preparation method of biologically active diphenyl heptane compound according to claim 1, it is characterised in that: step
Suddenly (2) preparative liquid chromatography, using ratio for 65:35 methanol-water as mobile phase, Detection wavelength be 208nm and 220nm,
Flow velocity is 12mL/min.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101979366A (en) * | 2010-09-26 | 2011-02-23 | 沈阳药科大学 | Diarylheptanoid compounds in curcuma zedoary and medicinal application thereof |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101979366A (en) * | 2010-09-26 | 2011-02-23 | 沈阳药科大学 | Diarylheptanoid compounds in curcuma zedoary and medicinal application thereof |
Non-Patent Citations (2)
| Title |
|---|
| 《生姜中二苯庚烷类化合物的抗氧化和细胞毒活性研究》;杨雷香等;《中国中药杂志》;20091231;第34卷(第3期);319-323 * |
| 《莪术油霜剂外用治疗银屑病的药效学及作用机制研究》;宋智琦等;《中国皮肤性病学杂志》;20011231;第15卷(第5期);301-303 * |
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