CN107337673A - A kind of Rutaecarpine gold salt and its synthetic method and application - Google Patents
A kind of Rutaecarpine gold salt and its synthetic method and application Download PDFInfo
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- CN107337673A CN107337673A CN201710733882.6A CN201710733882A CN107337673A CN 107337673 A CN107337673 A CN 107337673A CN 201710733882 A CN201710733882 A CN 201710733882A CN 107337673 A CN107337673 A CN 107337673A
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- rutaecarpine
- gold salt
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- chloroform
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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Abstract
The invention discloses a kind of Rutaecarpine gold salt and its synthetic method and application, belong to pharmaceutical technology field.Aim to provide a kind of Rutaecarpine gold salt and its synthetic method, and its new application in anti-tumor aspect.The structural formula of described Rutaecarpine gold salt is as follows：The present invention can be used for preparing antineoplastic.
Description
Technical field
The invention belongs to pharmaceutical technology field, especially a kind of Rutaecarpine gold salt and its synthetic method and application.
Background technology
Part selection of the present invention derives from Chinese medicine evodia alkaloid active ingredient Rutaecarpine (Rutaecarpine).
Since the successful use of the antitumor Metal Drugs of cis-platinum clinically, relative platinum complexes, and other metals are matched somebody with somebody
Compound, as the antitumor and anticancer agent research of gold complex also increasingly causes extensive concern.Rutaecarpine belongs to indole quinazoline life
The classical mother nucleus structure of alkaloids, such functional structure easily chelate generation complex or in the form of alkaloid salt with metal ion
In the presence of, the economic benefits and social benefits for being expected to play effective component of chinese medicine and metal ion after complexation of metal ions act synergistically, therefore gold ion with
The active fruit of medicinal cornel time alkali combines to form metal complex or gold ion salt compound is expected to similar to cisplatin medicine
Antitumor activity and there is the characteristics of hypotoxicity.
At present, some existing Rutaecarpine derivatives are developed the research as antineoplastic.But ground in the past
Study carefully the organic molecule stage that all rests on, and the metal salt of Rutaecarpine or complex not yet someone study.Therefore, still need
Want more preferable alternatives.
The content of the invention
For above-mentioned deficiency, of the invention first purpose is to provide a kind of Rutaecarpine gold salt；Second purpose be
The synthetic method of the Rutaecarpine gold salt is provided；3rd purpose is to provide the Rutaecarpine gold salt in anti-tumor aspect
Purposes.
In order to realize above-mentioned first purpose, technical scheme provided by the invention is such：A kind of Rutaecarpine gold
Salt, its structural formula are as follows：
In order to realize second purpose, technical scheme provided by the invention is such：A kind of evodia rutaecarpa as described above
The synthetic method of secondary alkali gold salt is：The ratio between amount by material is 1：0.5~3.0 Rutaecarpine and HAuCl4·4H2O distinguishes
After being dissolved in chloroform and methanol, mixing, heating response is filtered, is cooled to room temperature to complete, by the washing of gained crystal, is dried
Obtain Rutaecarpine gold salt compound.
Wherein, the Rutaecarpine and HAuCl4·4H2The ratio between O amount of material is 1：1.5~3.0.
Wherein, the addition of the chloroform is that every gram of Rutaecarpine adds 50~200mL, and the addition of methanol is every gram
HAuCl4·4H2O adds 40~100mL.
Wherein, the addition of the chloroform is that every gram of Rutaecarpine adds 55~166mL, and the addition of methanol is every gram
HAuCl4·4H2O adds 41~83mL.
Wherein, the mode of heating is water-bath, and heating-up temperature is 50~65 DEG C, and the heat time is 2~6 hours.
Wherein, the mode of heating is water-bath, and heating-up temperature is 55~65 DEG C, and the heat time is 3~5 hours.
Wherein, the washing is successively to be washed using petroleum ether and chloroform.
Wherein, after the crystal is is cooled to room temperature, slowly obtained by volatilization.
In order to realize above-mentioned 3rd purpose, technical scheme provided by the invention is such：A kind of Wu as described above
The fruit of medicinal cornel time alkali gold salt is used for the purposes for preparing antineoplastic.
Beneficial effects of the present invention：
The present invention is using Rutaecarpine as architecture basics, under condition of water bath heating, Rutaecarpine and HAuCl4·4H2O
Generation complex reaction obtains Rutaecarpine gold salt compound, and synthetic method is simple, gentle, reaction condition is easily controllable.
Rutaecarpine gold salt compounds on ovarian JEG-3 Skov3 has obvious inhibitory action, and IC50 values are
8.66 μM, good potential medical value is shown, can be as the metal antineoplastic of hypotoxicity.
Rutaecarpine derives from natural alkaloid, and raw material is natural, and product is readily synthesized, and synthesis provided by the invention
Method is simple, and the cost for synthesizing Rutaecarpine gold salt compound is low.
Brief description of the drawings
Fig. 1 is the infrared spectrogram of Rutaecarpine gold salt of the present invention；
Fig. 2 is the X-ray single crystal diffraction structure chart of Rutaecarpine gold salt of the present invention.
Embodiment
With reference to embodiment, the claim of the present invention is described in further detail, but not formed pair
Any restrictions of the present invention, any limited number of time modification made in the claims in the present invention protection domain, still the present invention's
In claims.
Embodiment 1
Weigh Rutaecarpine (0.03g, 0.1mmol), HAuCl4·4H2O (0.06g, 0.15mmol), is dissolved in 5ml respectively
Chloroform and 5ml methanol in, be placed in after mixing in 50ml round-bottomed flask, in 55 DEG C of heating water baths 3 hours, make it completely anti-
Should, filtering, at room temperature volatilization obtains light red bulk crystals, with petroleum ether, chloroform, is dried to obtain Rutaecarpine gold
Salt, yield 87.1%.
Product checking：Carry out infrared spectrum, the analysis of X-ray single crystal diffraction respectively to red solid product obtained above,
As shown in Fig. 1~2, wherein Fig. 1 is the infrared spectrogram of Rutaecarpine gold salt of the present invention；Fig. 2 is Wu of the present invention
The X-ray single crystal diffraction structure chart of the fruit of medicinal cornel time alkali gold salt.
The specific Spectral Characteristics of Fig. 1 are as follows：
IR spectrum:3457,1730,1296,1708,1642,1619,1580cm-1。
1730 be C=O characteristic absorption peak, 1619cm-1For C=N characteristic absorption peak, 1580cm-1For C-N feature
Absworption peak.
X-ray single crystal diffraction structure shows that central ion gold ion forms [AuCl with chloride binding4]2-Ion cluster,
The N-H of two Rutaecarpines nitrogen-atoms protonates with hydrogen ion combination, forms the Rutaecarpine gold salt of ionic.
It is Rutaecarpine gold salt compound to determine above-mentioned reddish crystals product, and its molecular formula is：C18H14AuCl4N3O,
Molecular weight is 627.1g/mol, and its chemical structural formula is as follows：
Application test of the product of the present invention in antineoplastic：
Tested using the anti tumor activity in vitro of Rutaecarpine gold salt compounds on ovarian cancer Skov3 tumor cell lines.
1st, cell line and cell culture
Oophoroma Skov3 tumor cell lines are selected in this experiment.
Cell line culture containing the small ox bloods of 10wt%, 100U/mL penicillin, 100U/mL streptomysins RPMI~1640 or
In DMEM nutrient solutions, 37 DEG C of 5%CO containing volumetric concentration are put2Cultivated in incubator.Inverted microscope observes cell growth status,
0.25% Trypsin Induced passes on, and growth period cell of taking the logarithm is used to test.
2nd, the preparation of testing compound
Rutaecarpine gold salt compound used is product made from the embodiment of the present invention 1, its purity >=95%, is passed through
RMPI1640 culture mediums are diluted to five concentration gradients successively, respectively 40,20,10,5,2.5 μm of ol/L, test 20 μm of ol/L
Inhibiting rate of the Rutaecarpine gold salt compound to different tumor cell proliferations under concentration.
3rd, cell growth inhibition test (mtt assay)
(1) take the logarithm the tumour cell in growth period, after Trypsin Induced, matched somebody with somebody with the nutrient solution containing 10% calf serum
The cell suspension that concentration is 5000/mL is made, is inoculated in every μ L of hole 190 in 96 well culture plates, makes cell density to be measured extremely
1000~10000/hole (edge hole is filled with sterile PBS)；
(2) 5%CO2, 37 DEG C of incubation 24h, bottom hole is paved with to cell monolayer, the medicine 10 of finite concentration gradient is added per hole
μ L, each concentration gradient set 4 multiple holes；
(3) 5%CO2, 37 DEG C are incubated 48 hours, are observed under inverted microscope；
(4) 10 μ L MTT solution (5mg/mL PBS, i.e. 0.5%MTT) is added per hole, continues to cultivate 4h；
(5) culture is terminated, carefully sucks nutrient solution in hole, 150 μ L DMSO are added per hole and fully dissolve first a ceremonial jade-ladle, used in libation precipitation, are shaken
Swing after device mixes, with wavelength be 570nm in ELIASA, reference wavelength is the OD value that 450nm determines each hole；
(6) while zeroing hole (culture medium, MTT, DMSO) is set, (the medicine dissolving of cell, same concentrations is situated between control wells
Matter, nutrient solution, MTT, DMSO).
(7) according to the OD value (OD values) measured, to judge living cells quantity, OD values are bigger, and cytoactive is stronger.Profit
Use formula：
Calculate the inhibiting rate of compound on tumor cell growth.
As a result show, Rutaecarpine gold salt compounds on ovarian cancer Skov3 tumor cell lines that there is obvious suppression to make
With IC50 values are 8.66 μM, are demonstrated by good potential medical value.
Embodiment 2
Weigh Rutaecarpine (3g, 10mmol), HAuCl4·4H2O (6g, 15mmol), 250ml chloroform is dissolved in respectively
In 250ml methanol, it is placed in after mixing in 1000ml round-bottomed flask, in 55 DEG C of heating water baths 3 hours, makes it completely anti-
Should, filtering, at room temperature volatilization obtains light red bulk crystals, with petroleum ether, chloroform, is dried to obtain Rutaecarpine gold
Salt, yield 83.5%.
Product inspection method is the same as embodiment 1.
Embodiment 3
Weigh Rutaecarpine (3g, 10mmol), HAuCl4·4H2O (6g, 15mmol), 250ml chloroform is dissolved in respectively
In 250ml methanol, it is placed in after mixing in 1000ml round-bottomed flask, in 65 DEG C of heating water baths 5 hours, makes it completely anti-
Should, filtering, at room temperature volatilization obtains light red bulk crystals, with petroleum ether, chloroform, is dried to obtain Rutaecarpine gold
Salt, yield 85.3%.
Product inspection method is the same as embodiment 1.
Embodiment 4
Take Rutaecarpine (3g, 10mmol), HAuCl4·4H2O (12g, 30mmol), be dissolved in respectively 250mL chloroform and
In 500mL methanol, it is placed in after mixing in 1000mL round-bottomed flask, in 55 DEG C of heating water baths 3 hours, it is reacted completely,
Filtering, at room temperature volatilization obtain light red bulk crystals, with petroleum ether, chloroform, are dried to obtain Rutaecarpine gold salt,
Yield is 82.4%.
Product inspection method is the same as embodiment 1.
Embodiment 5
Weigh Rutaecarpine (9g, 30mmol), HAuCl4·4H2O (6g, 15mmol), 500mL chloroform is dissolved in respectively
In 250mL methanol, it is placed in after mixing in 1000mL round-bottomed flask, in 65 DEG C of heating water baths 4 hours, makes it completely anti-
Should, filtering, at room temperature volatilization obtains light red bulk crystals, with petroleum ether, chloroform, is dried to obtain Rutaecarpine gold
Salt compound, yield 77.3%.
Product inspection method is the same as embodiment 1.
Above-described is only presently preferred embodiments of the present invention, all timess made in the range of the spirit and principles in the present invention
What modifications, equivalent substitutions and improvements etc., should be included in the scope of the protection.
Claims (10)
1. a kind of Rutaecarpine gold salt, it is characterised in that its structural formula is as follows：
A kind of 2. synthetic method of Rutaecarpine gold salt as claimed in claim 1, it is characterised in that
The ratio between amount by material is 1:0.5~3.0 Rutaecarpine and HAuCl4·4H2After O is dissolved in chloroform and methanol respectively,
Mixing, heating response are filtered, are cooled to room temperature to complete, by the washing of gained crystal, are drying to obtain.
3. the synthetic method of Rutaecarpine gold salt according to claim 2, it is characterised in that the Rutaecarpine and
HAuCl4·4H2The amount ratio of O material is 1:1.5~3.0.
4. the synthetic method of Rutaecarpine gold salt according to claim 2, it is characterised in that the addition of the chloroform
50~200mL is added for every gram of Rutaecarpine, the addition of methanol is every gram of HAuCl4·4H2O adds 40~100mL.
5. the synthetic method of Rutaecarpine gold salt according to claim 4, it is characterised in that the addition of the chloroform
55~166mL is added for every gram of Rutaecarpine, the addition of methanol is every gram of HAuCl4·4H2O adds 41~83mL.
6. the synthetic method of Rutaecarpine gold salt according to claim 2, it is characterised in that the mode of heating is water
Bath, heating-up temperature are 50~65 DEG C, and the heat time is 2~6 hours.
7. the synthetic method of Rutaecarpine gold salt according to claim 6, it is characterised in that the mode of heating is water
Bath, heating-up temperature are 55~65 DEG C, and the heat time is 3~5 hours.
8. the synthetic method of Rutaecarpine gold salt according to claim 2, it is characterised in that the washing is using stone
Oily ether and chloroform are successively washed.
9. the synthetic method of Rutaecarpine gold salt according to claim 2, it is characterised in that the crystal is to be cooled to
After room temperature, slowly obtained by volatilization.
10. a kind of Rutaecarpine gold salt as described in claim 1-9 is any is used for the purposes for preparing antineoplastic.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106317084A (en) * | 2016-08-19 | 2017-01-11 | 玉林师范学院 | Tryptanthrin copper complex with antitumor activity and synthetic method thereof |
| CN106632328A (en) * | 2016-09-28 | 2017-05-10 | 玉林师范学院 | Evodiamine copper salt compound with antitumor activity and synthesizing method thereof |
-
2017
- 2017-08-24 CN CN201710733882.6A patent/CN107337673A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106317084A (en) * | 2016-08-19 | 2017-01-11 | 玉林师范学院 | Tryptanthrin copper complex with antitumor activity and synthetic method thereof |
| CN106632328A (en) * | 2016-09-28 | 2017-05-10 | 玉林师范学院 | Evodiamine copper salt compound with antitumor activity and synthesizing method thereof |
Non-Patent Citations (4)
| Title |
|---|
| BRUNO BRUNI: "Structure and Cytotoxic Properties of Some Selected Gold(III) Complexes", 《CROATICA CHEMICA ACTA》 * |
| 余奇: "吴茱萸次碱的研究进展", 《药学实践杂》 * |
| 施鹏飞: "三价金配合物抗肿瘤活性研究", 《化学进展》 * |
| 郭惠: "吴茱萸次碱的合成、结构表征及体内抗肿瘤作用研究", 《化学与生物工程》 * |
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