CN103183597A - Diaryl neptanone compound having antineoplastic activity, preparing method and application - Google Patents
Diaryl neptanone compound having antineoplastic activity, preparing method and application Download PDFInfo
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- CN103183597A CN103183597A CN2011104556840A CN201110455684A CN103183597A CN 103183597 A CN103183597 A CN 103183597A CN 2011104556840 A CN2011104556840 A CN 2011104556840A CN 201110455684 A CN201110455684 A CN 201110455684A CN 103183597 A CN103183597 A CN 103183597A
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Abstract
The invention relates to a new diaryl neptanone compound, its chemical name is 1,7-di-(4-hydroxycyclohexyl phenyl ketone)-heptane-1,4-diene-3-ketone, and a structural formula is shown as follows. The diaryl neptanone compound is obtained from Loranthaceae plants through parasitism by the processes of collection, extraction, column chromatography and separation. The pharmacology experiments show that the diaryl neptanone compound has good antineoplastic activity.
Description
Technical field
The invention belongs to medicine and field of natural product chemistry, and in particular to a kind of new diaryl neptanone compound and preparation method thereof.
Background technology
Mistletoe is Loranthaceae plant mistletoeViscum coloratum (Komar.) Nakai drying stem and branch with leaf.Different name Chinese ilex, northern parasitism, Liu Jisheng, yellow parasitic, Mongolian oak are posted, parasitic, jelly is blue or green.In the broad-leaf forest for being born in the m of height above sea level 300~2000, parasitize on the arbors such as elm, willow, willow, robur, pear tree, Japanese plum, apple, Chinese ash, alder, lime tree.Winter to secondary spring is harvested, and removes thick stem, is cut off, and is dried, or is dried after steaming.It is mistletoe bitter, mild-natured, return liver and kidney channel, there is wind-damp dispelling, filling liver kidney, strengthening the bones and muscles, antiabortive member effect.For arthralgia pain due to rheumatism, soreness and weakness of waist and knees, soreness and weakness of waist and knees, muscles and bones are powerless, uterine bleeding through many, blood leaking in gestation, fetal irritability, have a dizzy spell.Its new curative effect in terms of cardiovascular system, antitumor, treatment hepatitis is constantly found in recent years.The main chemical compositions of mistletoe have flavonoids, triterpenes, organic acid, lignin, glycoside and a small amount of sterol, amino acid, volatile oil and inorganic constituents etc..
Diaryl neptanone compound is in the less discovery of plant kingdom, and these the new diarylheptanoid compounds found at present from mistletoe medicinal material are 1- alkenyl -3- ketone group -1,7- diarylheptanoid structures, are still undiscovered noval chemical compounds.
Silica gel has wide application study in terms of the extracting and developing purifying, preparation process reform, quality of the pharmaceutical preparations analysis of Natural Medicine Chemistry composition in recent years, and is explicitly shown out its unique effect.Using silica gel adsorption function and material similar compatibility principle can from Chinese medicine extract separation and purification active ingredient or active component, discard the dross and select the essential to greatest extent, promote modernization of cmm development.
The content of the invention
It is an object of the invention to provide a kind of new diaryl neptanone compound.
It is another object of the present invention to provide the preparation method of above-mentioned diaryl neptanone compound.
It is yet a further object of the present invention to provide the purposes of the compound.
Diaryl neptanone compound provided by the present invention, ketone group is located at C3, and C1 have alkene structures, and two aromatic radicals are located at C1 and C7 respectively, that is, belong to 1- alkene -3- ketone group -1,7- diaryl neptanone compounds, and with following general structure：
The present invention provides the chemical constitution and title of one of diaryl neptanone compound, i.e. 1,7- bis--(4- hydroxy phenyls)-heptane -1,4- diene -3- ketone, English entitled 1,7-bis (4-hydroxyphenyl)-Isosorbide-5-Nitrae-heptadien-3-one, its concrete structure formula is as follows：
The compound has following spectroscopic properties：1HNMR and13CNMR and HMBC spectrums are as shown in table 1.
MS data：For the compound, its high resolution mass spectrum provides molecular ion peak ESI-MS (negative ion mode): m/z = 295.1328 [M+H]+, 317.1156 [M+Na]+; HR-ESI-MS: m/z = 295.1328 [M+H]+ (calcd. for C19H19O3:295.1329), molecular formula：C19H18O3.The compound ms fragment feature derives from cracking mode as follows.
Diaryl neptanone compound provided by the present invention is to separate to prepare from Loranthaceae plant mistletoe, and its preparation method is comprised the following steps that：
（1）The drying stem branch of mistletoe is taken, alcohol reflux is extracted, and filtering, merging filtrate obtains alcohol extract, and alcohol extract is recovered under reduced pressure into ethanol to without alcohol taste, concentrate is obtained；
（2）The concentrate obtained is extracted with petroleum ether, ethyl acetate organic solvent successively, and combined ethyl acetate extract is recovered under reduced pressure, obtains Herba Visci extract；
（3）The Herba Visci extract of gained is dissolved with proper amount of methanol, and takes proper silica gel to mix sample, the sample mixed is fitted into the silicagel column pre-processed and uses chloroform-methanol（100：0~0:100）Gradient elution, obtains 180 flow points, wherein Fr 41~50 is through silica gel column chromatography, petroleum ether-acetone（10：1~1：1）Gradient elution, obtains 163 flow points, and wherein flow point 44~57 prepares liquid phase（Detection wavelength：210nm；Mobile phase：Methanol-water（60：40））Obtain noval chemical compound 1,7- bis--(4- hydroxy phenyls)-heptane -1,4- diene -3- ketone.
In the present invention, Loranthaceae plant is mistletoe.
In the present invention, extract solution is 95% ethanol solution.
Be in the present invention, during extraction with 8,95 % alcohol refluxs of 6,6 times of amounts extract 2,1.5 and 1.5 h, and merge extract solution.
In the present invention, using silica gel column chromatography twice, for the first time using chloroform-methanol system gradient elution, second using petroleum ether-acetone system gradient elution；When being prepared using preparation liquid phase, mobile phase uses methanol-water system.
In the present invention, during using silica gel column chromatography, use a dry method on a sample.
In the present invention, the pharmacological action of described diaryl neptanone compound is with notable antitumor activity.
In the present invention, resulting new diaryl neptanone compound has significant antitumor activity, and its preparing raw material wide material sources, and cost is not high, is compared with existing antitumoral compounds with stronger advantage, there is very gratifying application prospect.
Brief description of the drawings
Fig. 1 is the high resolution mass spectrum figure of 1,7- bis--(4- hydroxy phenyls)-heptane -1,4- diene -3- ketone.
Fig. 2 is the high resolution mass spectrum figure of 1,7- bis--(4- hydroxy phenyls)-heptane -1,4- diene -3- ketone.
Fig. 3 composes for the hydrogen of 1,7- bis--(4- hydroxy phenyls)-heptane -1,4- diene -3- ketone（1HNMR）Figure.
Fig. 4 composes for the carbon of 1,7- bis--(4- hydroxy phenyls)-heptane -1,4- diene -3- ketone（13CNMR）Figure.
Fig. 5 schemes for the HSQC of 1,7- bis--(4- hydroxy phenyls)-heptane -1,4- diene -3- ketone.
Fig. 6 is the extraction separation process figure of embodiment of the present invention 1,7- bis--(4- hydroxy phenyls)-heptane -1,4- diene -3- ketone.
Embodiment
The content of the invention is further illustrated with specific embodiment below.
It is prepared by the separation of 1,7- bis--(the 4- hydroxy phenyls)-heptane -1,4- diene -3- ketone of embodiment 1.
Vegetable material：Loranthaceae mistletoe mistletoe（Viscum coloratum (Komar.) Nakai）Drying stem branch.
Method for separating and preparing：Stem branch 5.0kg is dried in mistletoe, with 8,95 % alcohol refluxs of 6,6 times of amounts extract 2,1.5 and 1.5 h, filtering, merging filtrate is recovered under reduced pressure ethanol to without alcohol taste, obtains the ml of concentrate about 2000.Respectively with the ml of petroleum ether 2000, the ml of ethyl acetate 2000 respectively extraction 3 times, combined ethyl acetate extract is recovered under reduced pressure, obtains Herba Visci extract.By Herba Visci extract, proper amount of methanol dissolving, and proper silica gel is taken to mix sample.The sample mixed is fitted into the silicagel column pre-processed, using chloroform-methanol（100：0~0:100）Gradient elution, obtains 180 flow points, wherein Fr 41~50 is through silica gel column chromatography, petroleum ether-acetone（10：1~1：1）After gradient elution, 163 flow points are obtained, wherein Fr 44~57 is through preparing liquid phase（Detection wavelength；210nm；Mobile phase：Methanol-water（60：40））, obtain noval chemical compound 1,7- bis--(4- hydroxy phenyls)-heptane-Isosorbide-5-Nitrae-diene -3- ketone.
The anti tumor activity in vitro research of 1,7- bis--(the 4- hydroxy phenyls)-heptane -1,4- diene -3- ketone of embodiment 2.
1. instrument and material
1.1 instruments
U-1900 type spectrophotometers（Hitachi）, AB135-S type electronic balances（Mettler Toledo）, pH-2TC（0.01 grade）Precise digital display acidometer（The letter Instrument Ltd. in Shanghai）.
1.2 reagents
RPMI1640, penicillin, streptomysin, hyclone, NaCl, KCl, KH2PO4, Na2HPO4·12H2O, NaHCO3, dimethyl sulfoxide (DMSO)（DMSO）, cis-platinum（DDP）Standard items, trypsase, bromination -3- (4,5- dimethyl -2- thiazolyls) -2,5- diphenyltetrazolium bromides（MTT）, 1,7- bis--(4- hydroxy phenyls)-heptane-Isosorbide-5-Nitrae-diene -3- ketone.
1.3 experimental cells
HeLa Cells, SGC-7901gastriccarcinomacellline, MCF-7 Human Breast Cancer Cells, glioma U251 cells are attached cell by this laboratory passage conservation.
2. experimental method
2.1 tetrazolium bromide colorimetric tests（MTT）Detect anti tumor activity in vitro
Tetrazolium bromide colorimetric test（MTT）It is a kind of common method for detecting cell survival and growth.Dehydrogenase in living cells mitochondria can be metabolized the bromination -3- (4 of reduction yellow, 5- dimethyl -2- thiazolyls) -2,5- diphenyltetrazolium bromides [3- (4,5-dimethylthiazol-2yl) -2,5-diphenylterazoliumbromide, MTT] Formazan and it is deposited on for the bluish violet crystallization of slightly solubility in cell, and dead cell is without this function.Dimethyl sulfoxide (DMSO)（DMSO）The purple crystal in cell can be dissolved, its absorbance is determined at 492 nm wavelength with enzyme-linked immunosorbent assay instrument（OD values）, in the range of certain cell number, the amount of MTT crystals formation is directly proportional to cell number, can indirect reaction living cells quantity.
2.2 MTT experiment methods
Take the logarithm Hela, U251, MCF-7 cell in growth period, respectively with 4 × 104 cells·mL-1、5×104 cells·mL-1、4×104 cells·mL-1Density is inoculated in 96 well culture plates, per the μ L of hole 100, and dosing after culture 24h, administration group dosage is as shown in table 2.Set control group, administration group simultaneously.Every group is all provided with 3 multiple holes, per the μ L of hole dosing 100.Cultivate after 48 h, remove nutrient solution and decoction, add 5 gL per hole-1The μ L of the MTT 10 and μ L of nutrient solution 100, continue to cultivate 4 h, remove nutrient solution and MTT, and the μ L of DMSO 150, microoscillator vibration 10min are added per hole, is existed with ELIASAλ 492nmLower survey OD values, calculate inhibiting rate, IC50Value.
Growth inhibition ratio %=((control group mean OD value-medication group mean OD value)/（Control group mean OD value）〕×100%
The software Bliss method calculation of half inhibitory concentration of NOSA 2.30（IC50）
3. experimental result
The invention test result indicate that, compound 1,7- bis--(4- hydroxy phenyls)-heptane-Isosorbide-5-Nitrae-diene -3- ketone has certain inhibited proliferation, and in concentration dependant sexual intercourse, with good application, DEVELOPMENT PROSPECT.
Claims (5)
1. the compound with following structure, chemical name is 1,7- bis--(4- hydroxy phenyls)-heptane-Isosorbide-5-Nitrae-diene -3- ketone,
2. the preparation method of compound described in claim 1, comprises the following steps：
A. the preparation of mistletoe crude extract：Take mistletoe medicine materical crude slice appropriate, alcohol reflux is extracted, filtering, merging filtrate obtains alcohol extract, ethanol is recovered under reduced pressure to without alcohol taste in alcohol extract, crude extract is obtained；
B. the preparation of Herba Visci extract：Mistletoe crude extract is extracted 3 times, combined ethyl acetate extract is recovered under reduced pressure ethyl acetate, obtains Herba Visci extract with after isometric petroleum ether extraction 3 times with isometric ethyl acetate；
C. diaryl neptanone compound is refined：Take in Herba Visci extract, proper amount of methanol dissolving, silica gel mixed sample, the silicagel column that the sample mixed is fitted into pretreatment, with chloroform-methanol 100:0~0:100 progress column chromatographies obtain 180 flow points, and flow point 41~50 is through silica gel column chromatography, petroleum ether-acetone 10：1~1：1 gradient elution obtains 163 flow points, and flow point 44~57 is obtained through preparing liquid phase；The Detection wavelength 210nm of liquid phase is prepared, mobile phase is methanol：Water=60：40.
3. purposes of the compound of claim 1 in antineoplastic is prepared.
4. the purposes described in claim 3, wherein described tumour is breast cancer, the cancer of the uterus, cervical carcinoma, prostate cancer, lung cancer, colorectal cancer, black cancer, oophoroma.
5. the purposes described in claim 3, wherein described tumour is breast cancer, cervical carcinoma, glioma, stomach cancer.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112321479A (en) * | 2020-11-04 | 2021-02-05 | 吉林大学 | Indole-4-formaldehyde compound with antibacterial activity in parasitic loranthus, preparation method and application thereof |
| CN113861009A (en) * | 2021-11-23 | 2021-12-31 | 沈阳药科大学 | Mono-carbonyl curcumin analogue and preparation method and application thereof |
| CN114591267A (en) * | 2022-03-31 | 2022-06-07 | 沈阳药科大学 | Nitrogen-containing derivatives of monocarbonyl curcumin, and preparation method and application thereof |
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2011
- 2011-12-31 CN CN201110455684.0A patent/CN103183597B/en active Active
Non-Patent Citations (1)
| Title |
|---|
| CHATCHAWAN CHANGTAM ET AL.: "Isoxazole analogs of curcuminoids with highly potent multidrug-resistant antimycobacterial activity", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112321479A (en) * | 2020-11-04 | 2021-02-05 | 吉林大学 | Indole-4-formaldehyde compound with antibacterial activity in parasitic loranthus, preparation method and application thereof |
| CN112321479B (en) * | 2020-11-04 | 2022-02-08 | 吉林大学 | Indole-4-formaldehyde compound with antibacterial activity in parasitic loranthus, preparation method and application thereof |
| CN113861009A (en) * | 2021-11-23 | 2021-12-31 | 沈阳药科大学 | Mono-carbonyl curcumin analogue and preparation method and application thereof |
| CN113861009B (en) * | 2021-11-23 | 2024-04-05 | 沈阳药科大学 | Monocarbonyl curcumin analogue, and preparation method and application thereof |
| CN114591267A (en) * | 2022-03-31 | 2022-06-07 | 沈阳药科大学 | Nitrogen-containing derivatives of monocarbonyl curcumin, and preparation method and application thereof |
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