CN102617632B - Organic germanium complex, and preparation method and application thereof - Google Patents
Organic germanium complex, and preparation method and application thereof Download PDFInfo
- Publication number
- CN102617632B CN102617632B CN201210059684.3A CN201210059684A CN102617632B CN 102617632 B CN102617632 B CN 102617632B CN 201210059684 A CN201210059684 A CN 201210059684A CN 102617632 B CN102617632 B CN 102617632B
- Authority
- CN
- China
- Prior art keywords
- daphnetin
- solution
- complex
- preparation
- organogermanium
- 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.)
- Expired - Fee Related
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses an organic germanium complex and a preparation method and application thereof. The organic germanium complex is obtained by complexing germanium (IV) and daphnetin, and has a structural formula shown in the specification. The method for preparing the organic germanium complex comprises the following steps of: dissolving the daphnetin in water, regulating the pH value to be neutral, adding H2GeO3 for refluxing, filtering, and drying a filtrate by distillation under reduced pressure to obtain a yellow solid; and recrystallizing, and drying to obtain a powdery solid, namely the organic germanium complex. According to the organic germanium complex, the antioxidation and anti-tumor performance is obviously superior to that of the daphnetin, and the organic germanium complex has an application value in the preparation of antioxidation and anti-tumor medicines or health-care products.
Description
Technical field
The invention belongs to Natural Medicine Chemistry field, be specifically related to a kind of Organogermanium complex and its preparation method and application.
Background technology
Free radical, the hazardous compound producing in body oxidizing reaction, has strong oxidizing property, can damage tissue and the cell of body, and then causes chronic disease and aging effect.Excessive free radical can be induced Mitochondrial DNA Mutation and apoptosis, thereby organism is produced a series of serious diseases such as cancer, β-thalassemia, Heng Tingdunshi chorea.Reduce the harm of radical pair human body, except relying on interior free yl scavenge system, also will find and excavate exogenous free-radical scavengers.Therefore, exploitation has more strong anti-oxidation active medicine becomes one of current study hotspot.
Research in recent years shows, metal ion is incorporated in Chinese medicine organic composition and can makes it produce the synergy of forward.Germanium is the micro-metals that a kind of toxic side effect is less and useful to human body.Germanic compound has physiologically active widely, and the health substance of ginseng, Radix Codonopsis, the root of Dahurain angelica, matrimony vine, Ganoderma lucidum seu Japonicum, aloe and tealeaves etc. is all rich in organic germanium.Daphnetin, i.e. Daphnelin, is a kind of natural polyphenol compounds extracting from plant, it has very strong anti-oxidant activity.
Hu Daodao etc. had once reported the scavenging(action) (CHINA JOURNAL OF CHINESE MATERIA MEDICA, the 20th the 12nd phase of volume of nineteen ninety-five, 749 ~ 750) to superoxide radical of Daphnetin and copper (II) and zinc (II) title complex.Its result shows, different metals coordinates with Daphnetin to exist and interacts, and may bring stronger biological activity.Sun Zuomin etc. had once synthesized the title complex (chemical research and application, the 14th the 2nd phase of volume in 2002,194 ~ 196) of rare earth and Daphnetin formation, but it is not studied the drug effect of gained title complex.About germanium, the title complex that particularly germanium (IV) and Daphnetin form is there are no report at present.
Summary of the invention
The object of the present invention is to provide a kind of novel Organogermanium complex, described Organogermanium complex is coordinated and forms with Daphnetin by germanium (IV), and described Organogermanium complex has been introduced Ge-O group in Daphnetin, and its resistance of oxidation is promoted significantly.
Another object of the present invention is to provide the preparation method of described Organogermanium complex.
Another object of the present invention is to provide the application of described Organogermanium complex.
Above-mentioned purpose of the present invention is achieved by following technical solution:
A kind of Organogermanium complex, has structural formula as follows:
The preparation method of described Organogermanium complex, comprises the steps:
(1) prepare Ge (IV) solution;
(2) Daphnetin is dissolved in methyl alcohol, regulates pH value 6.8 ~ 7.4, Ge (IV) solution then step (1) being made is added in Daphnetin methanol solution, stirs 7 ~ 10 hours at 30 ~ 45 DEG C; Then filter, filtrate is used underpressure distillation evaporate to dryness, obtains yellow solid;
(3) by yellow solid dissolve with methanol, leave standstill to separating out yellow solid, yellow solid is through suction filtration and use methyl alcohol, water washing, and vacuum-drying, obtains powdery solid, and described powdery solid is Organogermanium complex.
As a kind of preferred version, in step (1), described Ge (IV) solution is germanic acid or inclined to one side germanic acid solution.
As more preferably scheme of one, in step (1), the preparation method of described germanic acid solution is preferably GeO
2in water, dissolve, at 90 DEG C, be stirred to and obtain colourless transparent solution, cooling.
As a kind of preferred version, in step (2), adopt the sodium hydroxide solution of 0.01M to regulate pH value.
As a kind of preferred version, in step (2), in the Daphnetin adding and Ge (IV) solution, the mol ratio of Ge (IV) is 1.6:1.
As a kind of preferred version, in step (2), Ge (IV) solution joins in Daphnetin methanol solution in the mode dripping.
As most preferably scheme of one, in step (2), described pH value most preferably is 7.
As most preferably scheme of one, in step (2), described reflux temperature most preferably is 35 DEG C.
As most preferably scheme of one, in step (2), described return time most preferably is 8 hours.
The application of described Organogermanium complex in anti-oxidant, the antitumor drug of preparation or healthcare products.Described Organogermanium complex, in the Daphnetin structure itself with strong anti-oxidation, introduce Ge-O group, significantly improved the oxidation-resistance of Daphnetin, therefore described Organogermanium complex can be used as anti-oxidant, antitumor, antibacterial and immunoregulatory potential drug.
Compared with prior art, the present invention has following beneficial effect:
The anti-oxidant activity of described Organogermanium complex has higher anti-oxidant activity than Daphnetin, compared with Daphnetin, under same concentrations, can improve 91.5% to the clearance rate of DPPH free radical;
The anti-oxidant activity of described Organogermanium complex has higher anti-tumor activity than Daphnetin, compared with Daphnetin, under same concentrations, can improve 33.7% to the inhibited proliferation of human liver cancer cell HepG2 and cervical cancer cell Hela;
The preparation method of described Organogermanium complex is simple, is easy to carry out scale operation.
Brief description of the drawings
Fig. 1 is Daphnetin Complex of Ge and the clearance rate experiment of Daphnetin to DPPH free radical;
Fig. 2 is Daphnetin Complex of Ge and the proliferation inhibition test of Daphnetin to human liver cancer cell HepG2;
Fig. 3 is Daphnetin Complex of Ge and the proliferation inhibition test of Daphnetin to human cervical carcinoma cell Hela.
Embodiment
Below in conjunction with specific embodiment, the present invention is further explained, but embodiments of the present invention is not limited in any way.
embodiment 1
(1) prepare H
2geO
3; In Erlenmeyer flask, add GeO
20.105 g and a small amount of distilled water, be heated to 90 DEG C with water bath with thermostatic control agitated pool and obtain colourless transparent solution, cooling rear stand-by.
(2) 0.284g Daphnetin is dissolved in methyl alcohol, uses the sodium hydroxide solution of 0.01M to regulate pH value 7, the H then step (1) being made
2geO
3be added in Daphnetin methanol solution, at 35 DEG C, stir 10 hours; Then filter, filtrate is used underpressure distillation evaporate to dryness, obtains yellow solid;
(3) by yellow solid dissolve with methanol, leave standstill to separating out yellow solid, yellow solid is through suction filtration and use methyl alcohol, water washing, and vacuum-drying, obtains powdery solid, and described powdery solid is Organogermanium complex, productive rate 65%.
(4) structural characterization of product: (1) m.p.>300 DEG C; (2) ultimate analysis: C, 41.23%; H, 4.97%; (3) UV spectrum: λ max=275 nm, 333nm; (4) infrared spectra (KBr pressed disc method): 1685 cm
-1(ν C=O), 1383 cm-1(ν C-O-C), 1178 cm
-1(ν C-O-C), 473 m(ν Ge-O); (5) ESI-MS:m/z=361.2 (M+H
+), m/z=383.3 (M+Na
+); (6) thermogravimetric analysis: 14.42(0-100 DEG C), 48.03(100-600 DEG C, 37.55(>600 DEG C) (7) 1HNMR (500 MHz, DMSO-d6): 7.263 (s, 1H, 4-H); 7.094 (d, 1H, 6-H); 6.782 (d, 1H, 7-H); 6.446 (d, 1H, 3-H); 5.823[s, 6H, (OCH
3)
2]
embodiment 2
(1) prepare H
2geO
3; In Erlenmeyer flask, add GeO
20.0105g and a small amount of distilled water, be heated to 90 DEG C with water bath with thermostatic control agitated pool and obtain colourless transparent solution, cooling rear stand-by;
(2) 0.284g Daphnetin is dissolved in methyl alcohol, uses the sodium hydroxide solution of 0.01M to regulate pH value 7.4, the H then step (1) being made
2geO
3be added in Daphnetin methanol solution, at 45 DEG C, reflux 8 hours; Then filter, filtrate is used underpressure distillation evaporate to dryness, obtains yellow solid;
(3) by yellow solid dissolve with methanol, leave standstill to separating out yellow solid, yellow solid is through suction filtration and use methyl alcohol, water washing, and vacuum-drying, obtains powdery solid, and described powdery solid is Organogermanium complex, productive rate 53%.
The product structure that embodiment 2 makes characterizes consistent with the product structure characterization parameter of embodiment 1.
Embodiment 3 tests DPPH free radical scavenging
Compound concentration is 1.0 × 10
-4(DPPH) ethanolic soln of mo1/L and the H of different concns
2d(is Daphnetin) and the D-Ge(IV) methanol solution of title complex (being Daphnetin germanium (IV) title complex).Get 2ml sample and 2mlDPPH solution and be added, leave standstill after 30 min, survey the absorbance value (A of solution at 517nm
sample). the absorbancy (A that replaces sample to record with 2.0 mL methyl alcohol
0).Press column count formula free radical scavenging activity, in triplicate, try to achieve the mean value (clearance rate=[(A of clearance rate
0-A
sample)/A
0] × 100%).
Experimental result is shown in Fig. 1, as can be seen from Figure 1, works as H
2the concentration of D reaches 30 × 10
-6when mol/L, gradually mild to the scavenging(action) of DPPH free radical, the highest clearance rate is less than 45%.D-Ge(IV) title complex to the clearance rate of DPPH free radical apparently higher than H
2d, especially concentration is 20 × 10
-6more than mol/L.When concentration is 30 × 10
-6when mol/L, D-Ge(IV) title complex exceeded 50% to the clearance rate of DPPH free radical; When concentration is 40 × 10
-6when mol/L, title complex has reached 85% left and right to the clearance rate of DPPH free radical.Experimental result shows, H
2d and Ge(IV) anti-oxidant activity that forms after title complex will be far away higher than former part H
2d, especially slightly more than high density.
Embodiment 4 suppresses experiment to the in-vitro multiplication of human tumor cells
Adopt mtt assay.Grouping take the logarithm vegetative period cell for experiment.Cell starting point concentration is 5 × 10
4/ ml, establishes blank group, and experimental group is respectively the H of different concns
2d and D-Ge(IV) after title complex effect human liver cancer cell HepG2 and cervical cancer cell Hela 24h, add MTT 10 μ l, leave standstill centrifugal abandoning supernatant after 4h, every hole adds DMSO150 μ l, dissolving to be crystallized.After 10 min, survey OD value with BIO-RAD type 450 enzyme-linked immunosorbent assay instruments in 490 wavelength places, calculate inhibiting rate, experiment repeats 3 times.
Inhibiting rate (%)=(control group A
490-experimental group A
490)/control group A
490× 100%
As can be seen from Figure 2, act on respectively after 24h with liver cancer cell HepG2, part Daphnetin does not only have restraining effect to the propagation of HepG2 cell, has on the contrary growth promotion trend; Daphnetin Complex of Ge is to significantly proliferation function always of its right side, and its restraining effect strengthens along with the increase of concentration.As can be seen from Figure 3, act on respectively after 24h with cervical cancer cell Hela, although Daphnetin and Daphnetin Complex of Ge all have inhibition proliferation function to it, but under same concentration, Daphnetin Complex of Ge is obviously better than Daphnetin to the restraining effect of Hela cell, especially in the time of the concentration of 150-250 μ mol/L, enhancing amplitude reaches 80%.
Experimental result shows, the Daphnetin Complex of Ge of different concns all has significant restraining effect to the propagation of human liver cancer cell HepG2 and cervical cancer cell Hela, and its restraining effect increases with the increase of drug level and time.
Claims (7)
1. an Organogermanium complex, is characterized in that, described Organogermanium complex is coordinated and forms with Daphnetin by germanium (IV), has structural formula as follows:
。
2. the preparation method of Organogermanium complex as claimed in claim 1, is characterized in that, comprises the steps:
(1) prepare Ge (IV) solution;
(2) Daphnetin is dissolved in methyl alcohol, regulates pH value 6.8 ~ 7.4, Ge (IV) solution then step (1) being made is added in Daphnetin methanol solution, stirs 7 ~ 10 hours at 30 ~ 45 DEG C; Then filter, filtrate is used underpressure distillation evaporate to dryness, obtains yellow solid;
(3) by yellow solid dissolve with methanol, leave standstill to separating out yellow solid, yellow solid is through suction filtration and use methyl alcohol, water washing, and vacuum-drying, obtains powdery solid, and described powdery solid is Organogermanium complex;
In step (1), described Ge (IV) solution is germanic acid or inclined to one side germanic acid solution.
3. the preparation method of Organogermanium complex as claimed in claim 2, is characterized in that, described germanic acid or the partially preparation method of germanic acid solution are by GeO
2in water, dissolve, at 90 DEG C, be stirred to and obtain colourless transparent solution, cooling.
4. the preparation method of Organogermanium complex as claimed in claim 2, is characterized in that, in step (2), adopts the sodium hydroxide solution of 0.01M to regulate pH value.
5. the preparation method of Organogermanium complex as claimed in claim 2, is characterized in that, in step (2), in the Daphnetin adding and Ge (IV) solution, the mol ratio of Ge (IV) is 1.6:1.
6. the preparation method of Organogermanium complex as claimed in claim 2, is characterized in that, it is characterized in that, in step (2), Ge (IV) solution joins in Daphnetin methanol solution in the mode dripping.
7. the application of Organogermanium complex in anti-oxidant, the antitumor drug of preparation or healthcare products as claimed in claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210059684.3A CN102617632B (en) | 2012-03-08 | 2012-03-08 | Organic germanium complex, and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210059684.3A CN102617632B (en) | 2012-03-08 | 2012-03-08 | Organic germanium complex, and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102617632A CN102617632A (en) | 2012-08-01 |
| CN102617632B true CN102617632B (en) | 2014-11-12 |
Family
ID=46557884
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210059684.3A Expired - Fee Related CN102617632B (en) | 2012-03-08 | 2012-03-08 | Organic germanium complex, and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102617632B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109453164B (en) * | 2018-10-23 | 2021-08-06 | 中国科学院成都生物研究所 | Anti-tumor combined medicine |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1169011A (en) * | 1965-10-11 | 1969-10-29 | Dynamit Nobel Ag | Thermostable Phenolates |
| CN1093710A (en) * | 1993-04-15 | 1994-10-19 | 贵州大学 | Theapolyhenol germanium and preparation method thereof |
| CN102250138A (en) * | 2011-06-08 | 2011-11-23 | 广东药学院 | Germatrane compound as well as preparation method and application thereof |
-
2012
- 2012-03-08 CN CN201210059684.3A patent/CN102617632B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1169011A (en) * | 1965-10-11 | 1969-10-29 | Dynamit Nobel Ag | Thermostable Phenolates |
| CN1093710A (en) * | 1993-04-15 | 1994-10-19 | 贵州大学 | Theapolyhenol germanium and preparation method thereof |
| CN102250138A (en) * | 2011-06-08 | 2011-11-23 | 广东药学院 | Germatrane compound as well as preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 王俊杰等，.槲皮素-锗配合物的合成及清除氧自由基活性的研究.《高师理科学刊》.2010,第30卷(第1期),第71-74页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102617632A (en) | 2012-08-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101249116B (en) | Waxberry polyphenol chromocor extract, and preparations and applications thereof | |
| CN104277134B (en) | A kind of preparation method and applications of the dictyophora fungus polysaccharide-chelates of zinc with anti-tumor activity | |
| CN101565411A (en) | Method for extracting fucoxanthin from brown algae | |
| CN102126941A (en) | Preparation method of euphorbia peplus plant extract for preparing antitumor medicament | |
| CN101337980B (en) | Ruthenium complexes for restraining DNA from topologizing isomerase , preparation method and application thereof | |
| CN102276753A (en) | Method for preparing polyporus selenium polysaccharide | |
| CN102241684B (en) | Preparation method of parthenolide | |
| CN102863452B (en) | Method for preparing parthenolide originated from magnolia delavayi, magnolia liliiflora and magnolia denudate | |
| CN109776693A (en) | The preparation method of Fuscoporia obliqua polysaccharide chelated zinc | |
| EP2828276A1 (en) | Rutin-rich extract and method of making same | |
| CN102617632B (en) | Organic germanium complex, and preparation method and application thereof | |
| CN113072595B (en) | Low-toxicity Pt complex and preparation method and application thereof | |
| CN102093383A (en) | Potassium cantharidate and preparation method thereof | |
| CN102250110B (en) | Magnesium cantharidate and preparation method thereof | |
| CN109771475A (en) | A method of extracting polyphenol from purple perilla seed shell | |
| CN104684882A (en) | Coriolus versicolor extracts, methods of isolating biologically-active compounds, and uses thereof | |
| CN104262130B (en) | A kind of naphthoquinone compound of ocean microorganism, preparation method and its usage | |
| CN102127089B (en) | Method for extracting camptothecin | |
| CN102079739B (en) | Daidzein derivative, preparation method and application thereof | |
| CN1187357C (en) | Calcarisporin B1 and extracting method and use in anti-tumor medicine | |
| CN103214502A (en) | Binuclear zinc complex and preparation method and applications thereof | |
| CN107137448A (en) | A kind of short fruit cuckoo antioxidant extract and its preparation method and application | |
| CN102727493B (en) | Applications of TEMPOL derivatives as anti-tumor drugs | |
| CN107056818A (en) | The synthesis preparation method of Macaline A derivative and application | |
| CN114957340B (en) | Preparation method and application of binuclear iridium complex for inducing iron death |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20141112 Termination date: 20210308 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |