CN108912149B - Copper compound with 2-acetyl-3-ethylpyrazine thiosemicarbazone as ligand and synthetic method and application thereof - Google Patents
Copper compound with 2-acetyl-3-ethylpyrazine thiosemicarbazone as ligand and synthetic method and application thereof Download PDFInfo
- Publication number
- CN108912149B CN108912149B CN201810661502.7A CN201810661502A CN108912149B CN 108912149 B CN108912149 B CN 108912149B CN 201810661502 A CN201810661502 A CN 201810661502A CN 108912149 B CN108912149 B CN 108912149B
- Authority
- CN
- China
- Prior art keywords
- copper compound
- acetyl
- ethylpyrazine
- methanol
- reaction
- 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
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic System
- C07F1/005—Compounds containing elements of Groups 1 or 11 of the Periodic System without C-Metal linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The invention discloses a copper compound taking 2-acetyl-3-ethylpyrazine thiosemicarbazone as a ligand and a synthesis method and application thereof. The synthetic method of the copper compound comprises the following steps: taking 2-acetyl-3-ethylpyrazine and thiosemicarbazide, reacting by taking methanol as a solvent, transferring the reaction product into a beaker after the reaction, volatilizing and crystallizing to obtain a ligand 2-acetyl-3-ethylpyrazine thiosemicarbazone crystal, filtering the crystal, and washing the crystal by using methanol; taking ligand 2-acetyl-3-ethyl pyrazine thiosemicarbazone and CuCl2Or CuBr2And a mixed solvent of acetonitrile and methanol, transferring the reactant to a beaker for standing, cooling, volatilizing for crystallization, and collecting crystals after crystallization, namely synthesizing the target compound. The research on the activity of the synthesized copper compound against glioma and drug-resistant strains thereof in vitro shows that the copper compound forms a thiosemicarbazone copper complex with metal copper, the activity is greatly improved, the compound has more excellent glioma-resistant activity, and the drug resistance is overcome to a certain extent.
Description
Technical Field
The invention relates to synthesis of a copper compound, in particular to a copper compound taking 2-acetyl-3-ethylpyrazine thiosemicarbazone as a ligand, and a synthesis method and application thereof.
Background
Brain glioma is the primary intracranial malignant tumor with the highest incidence rate, which accounts for about 46 percent of intracranial tumors, and the cure rate of the existing treatment means such as operation, radiotherapy and chemotherapy is not lower than 30 percent. At present, brain tumor treatment medicines commonly used in clinic are small molecular medicines, but face a plurality of severe tests in the using process. 1) Due to the influence of the properties of the drugs, many anti-infection or anti-tumor drugs are insoluble small molecular drugs, which brings difficulty to clinical administration, especially intravenous administration; 2) drug resistance, either of the causative agent of the infection or tumor-initiating tumor cells, is likely to develop after multiple consecutive administrations, rendering the treatment ineffective.
At present, the thiosemicarbazone for synthesizing the copper complex has many advantages, for example, the synthesis of the 2-acetylpyridine thiosemicarbazone copper complex is studied, only the bacteriostasis is studied, other mechanisms are not studied, 2-benzopyridine three-class heterocyclic thiosemicarbazone Schiff base compounds are also studied, the application synthesizes the copper compound by taking the 2-acetyl-3-ethylpyrazine thiosemicarbazone as a ligand, and research experiments on the activity of the anti-glioma and drug-resistant strains thereof are studied, so that the anti-glioma effect is very strong, and the drug resistance is overcome to a certain extent.
Through retrieval, few compounds with the structure are reported, and the application of the compounds in glioma activity is not seen.
Disclosure of Invention
The invention aims to provide a copper compound taking 2-acetyl-3-ethylpyrazine thiosemicarbazone as a ligand, and anti-glioma and drug-resistant strain activity experiments of the copper compound prove that the copper compound has a strong anti-tumor effect and overcomes drug resistance to a certain extent.
The invention also provides a synthetic method of the copper compound, which is simple to operate and convenient to implement.
The invention also provides application of the copper compound in preparing anti-glioma drugs.
The technical scheme for realizing the purpose of the invention is as follows:
a copper complex using 2-acetyl-3-ethyl pyrazine thiosemicarbazone as ligand has a structural formula shown in formula C1-C6,
the synthetic route for the copper compounds of the above formula C1-C6 is as follows:
the method for synthesizing the copper compound shown in the formula C1-C6 comprises the following steps:
(1) taking 2-acetyl-3-ethylpyrazine and thiosemicarbazide, reacting by taking methanol as a solvent, transferring the reaction product into a beaker after the reaction, volatilizing and crystallizing to obtain a ligand 2-acetyl-3-ethylpyrazine thiosemicarbazone crystal, filtering the crystal, and washing the crystal for 2-3 times by using methanol;
(2) taking the ligand 2-acetyl-3-ethyl pyrazine thiosemicarbazone and CuCl in the step (1)2Or CuBr2And a mixed solvent of acetonitrile and methanol, transferring the reactant to a beaker for standing, cooling, volatilizing for crystallization, and collecting crystals after 5-7 days of crystallization to synthesize the target compound.
In the synthesis method, the methanol preferably adopts 20-80% by volume concentration, and the acetonitrile adopts analytically pure.
In the above synthesis method, the reaction is preferably performed in the range from 20 ℃ to 70 ℃ to the reflux temperature of the solvent, the reaction can be performed under normal temperature conditions, a conventional heating reaction or a reflux reaction, preferably the reflux reaction, and whether the reaction is complete or not can be followed and detected by Thin Layer Chromatography (TLC).
In step (1) of the above synthesis method, the ratio of the amounts of the substances of 2-acetyl-3-ethylpyrazine and thiosemicarbazide is a stoichiometric ratio, typically 1: 1; the solvent is preferably used for dissolving raw materials participating in the reaction, and in general, 1mmol of thiosemicarbazide is dissolved by 4-10 mL of solvent, and then 2-acetyl-3-ethylpyrazine is added in a certain proportion.
In the step (2) of the synthesis method, the filtrate obtained by the reaction is kept stand and crystallized, and crystals are collected. In this step, usually, standing and crystallization are performed at room temperature. Furthermore, when standing for crystallization, a layer of film is covered on the opening of the container for containing the filtrate, and then a plurality of small holes are formed on the film to slowly volatilize the solvent, so that a better crystallization effect is obtained. In the step, ligands of 2-acetyl-3-ethyl pyrazine thiosemicarbazone and CuCl2/CuBr2The ratio of the amounts of substances (a) to (b) is a stoichiometric ratio of 1: 1.
in the step (2) of the above synthesis method, the solvent is preferably used in an amount capable of dissolving the raw material for the reaction, and usually 1mmol of 2-acetyl-3-ethylpyrazine thiosemicarbazone is dissolved in 4 to 10mL of the solvent, and CuCl2Or CuBr2Dissolve with 1mL of solvent. In a specific dissolution step, the ligands 2-acetyl-3-ethylpyrazine thiosemicarbazone and CuCl can be dissolved2Or CuBr2Dissolving the raw materials respectively by using solvents, and mixing the raw materials together for reaction; the ligands 2-acetyl-3-ethyl pyrazine thiosemicarbazone and CuCl can also be used2Or CuBr2And adding a solvent for dissolving after mixing. The mixture ratio of the acetonitrile to the methanol can be combined randomly, and the optimal mixture ratio is 3: 1.
The invention further comprises an anti-glioma drug prepared by taking the copper complex C1-C6 as an active ingredient.
Compared with the prior art, the invention provides a copper (II) metal complex of a novel ligand 2-acetyl-3-ethylpyrazine thiosemicarbazone and researches on the activity of six copper complexes in vitro anti-glioma and drug-resistant strains thereof show that thiosemicarbazone also has anti-tumor activity but low activity, forms a thiosemicarbazone copper complex with metal copper, greatly improves the activity of the copper complex, has more excellent anti-glioma activity, and overcomes drug resistance to a certain extent.
Drawings
FIG. 1 is a single crystal structural diagram of a C1 copper compound synthesized in example 1.
FIG. 2 is a single crystal structural diagram of a C2 copper compound synthesized in example 2.
FIG. 3 is a single crystal structural diagram of a C3 copper compound synthesized in example 3.
FIG. 4 is a single crystal structural view of a C4 copper compound synthesized in example 4.
FIG. 5 is a single crystal structural diagram of a C5 copper compound synthesized in example 5.
FIG. 6 is a single crystal structural view of a C6 copper compound synthesized in example 6.
FIG. 7 is a structural diagram of a ligand of the copper compound of examples 1 to 6.
Detailed Description
The present invention will be better understood from the following detailed description taken in conjunction with the specific embodiments and the accompanying drawings, but the present invention is not limited to the following embodiments.
Example 1: synthesis of C1 copper Compound
The specific synthesis method comprises the following steps:
(1) dissolving 10mmol of 2-acetyl-3-ethylpyrazine in 20mL of methanol, stirring at 60 ℃ for 15min, then dropwise adding 20mL of 10mmol of thiosemicarbazide in methanol into the solution, refluxing and stirring at 60 ℃ for reaction for 12h, cooling to room temperature, pouring into a beaker for volatilization, filtering the obtained light yellow crystal, and washing with methanol for 3 times to obtain a ligand (L1);
(2) will contain CuCl2·2H230mL of acetonitrile solution of O (170.48mg,1mmol) is added into 10mL of methanol solution containing 1mmol of the L1 ligand, the mixture is refluxed and stirred for 24 hours at 65 ℃, the solution after reaction is filtered into a 50mL beaker and sealed by a preservative film, 15 holes are pricked by a needle to volatilize for several days at normal temperature, and a tawny crystal (C1) is obtained, wherein the single crystal structure of the tawny crystal is shown in figure 1;
yield: 66%, IR, cm-1:3381(S, amide),3177(S, NH),1631(S),1551(S),1475(S),1424(S, aromatic),1350(S, C ═ N),1297(S, thioamide),1205(S),1155(S),1122(m),1032(m, C-H),867(m, C ═ S),783(S), EIMS m/z: calcd for C9H11N5SClCu,318.97[M-H]+。
Example 2: synthesis of C2 copper Compound
The specific synthesis method comprises the following steps:
(1) dissolving 10mmol of 2-acetyl-3-ethylpyrazine in 20mL of methanol, stirring at 60 ℃ for 15min, then dropwise adding 20mL of 10mmol of 4-methyl thiosemicarbazide methanol solution into the solution, refluxing and stirring at 60 ℃ for reaction for 12h, cooling to room temperature, pouring into a beaker for volatilization, filtering the obtained light yellow crystals, and washing with methanol for 3 times to obtain a ligand (L2);
(2) will contain CuBr2(223.35mg,1mmol) of 30mL of acetonitrile, dropwise adding the solution into 10mL of methanol solution containing 1mmol of the L2 ligand, refluxing and stirring at 65 ℃ for 24 hours, filtering the solution after reaction into a 50mL beaker, sealing the beaker with a preservative film, and pricking 15 holes with needles to volatilize for several days at normal temperature to obtain a yellow brown crystal (C2), wherein the single crystal structure of the crystal is shown in FIG. 2;
yield: 59%, IR, cm-1:IR,cm-1:3308(s,amide),2936(s,NH),1533(s),1505(s),1486(s),1390(s,aromatic),1281(s,C＝N),1236(s,thioamide),1162(s),1097(m),1061(m),985(m,C-H),853(m,C＝S),819(s).EIMS m/z:calcd for C10H14N5SBrCu,377.94[M-H]+。
Example 3: synthesis of C3 copper Compound
The specific synthesis method comprises the following steps:
(1) dissolving 10mmol of 2-acetyl-3-ethylpyrazine in 20mL of methanol, stirring at 60 ℃ for 15min, then dropwise adding 20mL of 10mmol of 4-phenyl-3-thiosemicarbazide methanol solution into the solution, refluxing and stirring at 60 ℃ for reaction for 12h, cooling to room temperature, pouring into a beaker for volatilization, filtering the obtained light yellow crystals, and washing with methanol for 3 times to obtain a ligand (L3);
(2) will contain CuBr2(223.35mg,1mmol) of 30mL of acetonitrile, dropwise adding the solution into 10mL of methanol solution containing 1mmol of the L3 ligand, refluxing and stirring at 65 ℃ for 24 hours, filtering the solution after reaction into a 50mL beaker, sealing the beaker with a preservative film, and pricking 15 holes with needles to volatilize for several days at normal temperature to obtain a yellow brown crystal (C3), wherein the single crystal structure of the crystal is shown in FIG. 3;
yield: 53%, IR, cm-1:3301(s, amide),2930(s, NH),1597(s),1573(s),1536(s),1488(m, aromatic),1399(s, C ═ N),1320(s,thioamide),1249(s),1148(s),983(m),857(m,C-H),760(m,C＝S),693(s).EIMS m/z:calcd for C15H16N5BrCu,440.94[M-Br]+。
Example 4: synthesis of C4 copper Compound
The specific synthesis method comprises the following steps:
(1) dissolving 10mmol of 2-acetyl-3-ethylpyrazine in 20mL of methanol, stirring at 60 ℃ for 15min, then dropwise adding 20mL of 10mmol of 4, 4-dimethyl-3-semicarbazide methanol solution into the solution, refluxing and stirring at 60 ℃ for reaction for 12h, cooling to room temperature, pouring into a beaker for volatilization, filtering the obtained light yellow crystals, and washing with methanol for 3 times to obtain a ligand (L4);
(2) will contain CuBr2(223.35mg,1mmol) of 30mL of acetonitrile, dropwise adding the solution into 10mL of methanol solution containing 1mmol of the L4 ligand, refluxing and stirring at 65 ℃ for 24 hours, filtering the solution after reaction into a 50mL beaker, sealing the beaker with a preservative film, and pricking 15 holes with needles to volatilize for several days at normal temperature to obtain a yellow brown crystal (C4), wherein the single crystal structure of the crystal is shown in FIG. 4;
yield: 72%, IR, cm-1:3433(S, amide),2974 (S), 2925(m, aromatic hydrogen),1631(S),1532(S, aromatic),1389(S, C ═ N),1285(S, thioamide),1235(S),1154(S),1088(m),1058(m, C-H),865(w, C ═ S), EIMS m/z: calcd for C (m, C ═ S), EIMS m/z11H16N5BrCu,392.94[M-Br]+。
Example 5: synthesis of C5 copper Compound
The specific synthesis method comprises the following steps:
(1) dissolving 10mmol of 2-acetyl-3-ethylpyrazine in 20mL of methanol, stirring at 60 ℃ for 15min, then dropwise adding 20mL of 10mmol of 4, 4-diethyl-3-semicarbazide methanol solution into the solution, reacting at 60 ℃ under reflux and stirring for 12h, cooling to room temperature, pouring into a beaker for volatilization, filtering the obtained light yellow crystals, washing with methanol for 3 times to obtain ligand (L5)
(2) Will contain CuBr2(223.35mg,1mmol) of 30mL of acetonitrile, was added dropwise to a solution of 1mmol of the above L5 ligand in 10mL of methanol, the mixture was stirred at 65 ℃ under reflux for 24 hours, and the reaction solution was filtered to 50mL of a calcined substanceSealing the cup by using a preservative film, and pricking 15 holes with needles to volatilize for several days at normal temperature to obtain a tawny crystal (C5), wherein the single crystal structure of the tawny crystal is shown in figure 5;
yield: 60%, IR, cm-1:3433(S, amide),2973(S),2820(m, aromatic hydrogen),1503(S),1449(S),1389(S, aromatic),1359(S, C ═ N),1320(S, thioamide),1256(S),1192(S),1144(m),850(m, C ═ S),629(S), EIMS m/z: calcd for C13H21N5BrCu,420.97[M-Br]+。
Example 6: synthesis of C6 copper Compound
The specific synthesis method comprises the following steps:
(1) dissolving 10mmol of 2-acetyl-3-ethylpyrazine in 20mL of methanol, stirring at 60 ℃ for 15min, dropwise adding 20mL of 10mmol of 3-piperidyl thiosemicarbazide acetonitrile solution into the solution, refluxing and stirring at 60 ℃ for reaction for 12h, cooling to room temperature, pouring into a beaker for volatilization, filtering the obtained light yellow crystals, washing with methanol for 3 times to obtain a ligand (L6)
(2) Will contain CuBr2(223.35mg,1mmol) of 30mL of acetonitrile, dropwise adding the solution into 10mL of methanol solution containing 1mmol of the L5 ligand, refluxing and stirring at 65 ℃ for 24 hours, filtering the solution after reaction into a 50mL beaker, sealing the beaker with a preservative film, and pricking 15 holes with needles to volatilize for several days at normal temperature to obtain a yellow brown crystal (C6), wherein the single crystal structure of the crystal is shown in FIG. 5;
yield: 47%, IR, cm-1:3435(S, amide),2911(S),1632(S),1582(S),1495(S, aromatic),1385(S, C ═ N),1328(S, thioamide),1156(S),1058(S),881(S),755(m, C ═ S),509(S), EIMS m/z: calcd for C14H19ClN5BrCu,432.97[M-Br]+。
To illustrate the copper compound pairs of the present invention using thiosemicarbazide as a ligand, the applicant conducted anti-tumor activity experiments on both the above compounds and the compounds obtained in examples 1 to 6.
In-vitro antitumor activity test of compound
1. Inoculation and culture of cells
The selected cell lines were all incubated at 37 ℃ with 5% CO2Incubator under sufficient humidifying conditionThe cells were cultured in DMEM medium containing 10% and 1% P/S (penicillin streptomycin). And (3) observing the growth condition of the cells by using an inverted microscope, changing the liquid every other day, carrying out digestion and passage by using 0.25% trypsin when the cell density reaches 90%, usually carrying out passage for 3-4 times, and taking the cells in the logarithmic growth phase for experiment.
2. Cell growth inhibition assay (MTT method)
MTT colorimetric method is a method for detecting cell growth and survival. The detection principle is as follows: unlike dead cells, exogenous MTT can be reduced to water-insoluble blue-violet crystalline Formazan (Formazan) by succinate dehydrogenase in mitochondria of living cells and deposited in cells. Methanezan in cells can be solubilized by dimethyl sulfoxide (DMSO), and the number of viable cells can be indirectly reflected by measuring the light absorption at 490nm using an enzyme linked immunosorbent assay. Within a certain range of cell number, MTT crystals are formed in an amount proportional to the cell number. The method is widely used for activity detection of some bioactive factors, large-scale antitumor drug screening, cytotoxicity test, tumor radiosensitivity determination and the like, and has the characteristics of high sensitivity, economy and the like.
3. Detailed description of the preferred embodiment
Cells in logarithmic growth phase were seeded in 96-well plates at 37 ℃ with 5% CO in 180. mu.L (about 4500-2Culturing for 24h under fully humidified conditions. After the cells adhere to the wall, samples are added according to the amount of 20 mu L per well, each sample is provided with 5 multiple wells, and corresponding blank control is set at the same time. And (3) continuing culturing for 48h, adding 10 mu L of MTT reagent (the concentration is 5mg/mL) into each hole, continuing incubating for 4h, then sucking and removing the supernatant, adding 100 mu L of DMSO into each hole, and slightly shaking for reaction for 5-8 min to fully dissolve the crystal particles. Zeroing the blank control group, and measuring the absorbance value after removing the background light absorption value by an enzyme-linked immunosorbent assay (using an enzyme-linked immunosorbent assay) at 490nm
Value), calculating cell proliferation inhibition rate, and continuously using 5 concentration gradients to continuously make IC of corresponding cell strain for preliminarily screening test compounds with good anti-tumor effect50Values, all experiments were repeated 3 times and takenAverage value. The experimental results are detailed in table 1 below.
TABLE 1 half Inhibitory Concentration (IC) of the compounds against different tumor cell lines50，μM)
The experimental results show that: compared with the ligand of the 2-acetyl-3-ethylpyrazine thiosemicarbazone copper complex, the complex has more excellent antitumor activity on glioma and drug-resistant strains thereof, has relatively low toxicity on normal cells and reduces drug resistance to a certain degree.
Claims (6)
1. A synthetic method of a copper compound taking 2-acetyl-3-ethylpyrazine thiosemicarbazone as a ligand is characterized in that: the structural formula of the copper compound is shown as the following formula C1-C6,
the synthetic route of the copper compound is as follows:
the method for synthesizing the copper compound shown as C1-C6 comprises the following steps:
(1) taking 2-acetyl-3-ethylpyrazine and thiosemicarbazide, reacting by taking methanol as a solvent, transferring the reaction product into a beaker after the reaction, volatilizing and crystallizing to obtain a ligand 2-acetyl-3-ethylpyrazine thiosemicarbazone crystal, filtering the crystal, and washing the crystal by using methanol;
(2) taking the ligand 2-acetyl-3-ethylpyrazine condensed in the step (1)Thiosemicarbazide and CuCl2Or CuBr2And a mixed solvent of acetonitrile and methanol, transferring the reactant to a beaker for standing, cooling, volatilizing for crystallization, and collecting crystals after crystallization, namely synthesizing the target compound.
2. The method for synthesizing a copper compound according to claim 1, wherein: the methanol is methanol with the volume concentration of 20-80%, and the acetonitrile is analytically pure.
3. The method for synthesizing a copper compound according to claim 1, wherein: the reaction is performed by adopting reflux reaction at the reflux temperature of the solvent, and whether the reaction is completely detected by adopting thin layer chromatography tracking.
4. The method for synthesizing a copper compound according to claim 1, wherein: in the step (1), the amount ratio of the 2-acetyl-3-ethylpyrazine to the thiosemicarbazide is a stoichiometric ratio and is 1: 1; the solvent is preferably used in an amount capable of dissolving the raw materials participating in the reaction.
5. The method for synthesizing a copper compound according to claim 1, wherein: in the step (2), standing and crystallizing the filtrate obtained by the reaction, and collecting crystals; ligands 2-acetyl-3-ethylpyrazine thiosemicarbazone and CuCl2Or CuBr2The ratio of the amounts of substances (a) to (b) is a stoichiometric ratio of 1: 1;
the dosage of the solvent is suitable for dissolving the raw materials participating in the reaction;
the acetonitrile methanol is 3: 1.
6. Use of a copper compound prepared by the method of synthesizing a copper compound according to claim 1 in the preparation of an anti-glioma drug.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810661502.7A CN108912149B (en) | 2018-06-25 | 2018-06-25 | Copper compound with 2-acetyl-3-ethylpyrazine thiosemicarbazone as ligand and synthetic method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810661502.7A CN108912149B (en) | 2018-06-25 | 2018-06-25 | Copper compound with 2-acetyl-3-ethylpyrazine thiosemicarbazone as ligand and synthetic method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108912149A CN108912149A (en) | 2018-11-30 |
| CN108912149B true CN108912149B (en) | 2020-12-22 |
Family
ID=64420690
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810661502.7A Expired - Fee Related CN108912149B (en) | 2018-06-25 | 2018-06-25 | Copper compound with 2-acetyl-3-ethylpyrazine thiosemicarbazone as ligand and synthetic method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108912149B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109651414B (en) * | 2019-01-16 | 2020-12-22 | 广西师范大学 | Indium compound with 2, 6-diacetyl pyridine thiosemicarbazone as ligand and synthetic method and application thereof |
| CN109796497B (en) * | 2019-01-16 | 2020-12-22 | 广西师范大学 | Bismuth compound with 2-acetyl-3-ethylpyrazine thiosemicarbazone as ligand and synthesis method thereof |
| CN109796501A (en) * | 2019-03-28 | 2019-05-24 | 广西师范大学 | Using human serum albumins as the synthetic method and application of platinum (II) metal composite of carrier |
| CN110698511B (en) * | 2019-11-15 | 2021-09-14 | 广西师范大学 | Tin complex with 2-pyridinecarboxaldehyde thiosemicarbazone as ligand and synthesis method thereof |
| CN111620913B (en) * | 2020-07-08 | 2021-09-03 | 广西师范大学 | Ruthenium complex with thiosemicarbazone as ligand and application thereof |
| CN112079851B (en) * | 2020-09-22 | 2021-09-10 | 广西师范大学 | Gold complex of FTO (fluorine-doped tin oxide) small-molecule inhibitor and synthetic method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19510229A1 (en) * | 1995-03-23 | 1996-09-26 | Keppler Bernhard K Priv Doz Dr | Bismuth complexes with tropolone, thiosemicarbazone or di:thiocarbazonic acid ester cpds. |
| CN104844631A (en) * | 2015-05-15 | 2015-08-19 | 广西师范大学 | Copper metal complex and compound prepared from copper metal complex and human serum albumin as well as synthesis method and application thereof |
| CN109796497A (en) * | 2019-01-16 | 2019-05-24 | 广西师范大学 | It is a kind of using 2- acetyl group -3- ethyl pyrazine thiosemicarbazones as the bismuth compound of ligand and its synthetic method |
-
2018
- 2018-06-25 CN CN201810661502.7A patent/CN108912149B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19510229A1 (en) * | 1995-03-23 | 1996-09-26 | Keppler Bernhard K Priv Doz Dr | Bismuth complexes with tropolone, thiosemicarbazone or di:thiocarbazonic acid ester cpds. |
| CN104844631A (en) * | 2015-05-15 | 2015-08-19 | 广西师范大学 | Copper metal complex and compound prepared from copper metal complex and human serum albumin as well as synthesis method and application thereof |
| CN109796497A (en) * | 2019-01-16 | 2019-05-24 | 广西师范大学 | It is a kind of using 2- acetyl group -3- ethyl pyrazine thiosemicarbazones as the bismuth compound of ligand and its synthetic method |
Non-Patent Citations (3)
| Title |
|---|
| Antifungal and antitumor activity of heterocyclic thiosemicarbazones and their metal complexes: current status;Anthony E. Liberta 等;《BioMetals》;19921231;第5卷;第121-126页 * |
| Examination of the Impact of Copper(II) α-(N)-Heterocyclic Thiosemicarbazone Complexes on DNA Topoisomerase IIα;James T. Wilson 等;《Chem. Res. Toxicol》;20160316;第29卷;第649-658页 * |
| Role of Metalation in the Topoisomerase IIr Inhibition and Antiproliferation Activity of a Series of alpha-Heterocyclic-N4-Substituted Thiosemicarbazones and Their Cu(II) Complexes;Brian M. Zeglis 等;《J. Med. Chem.》;20110310;第54卷;第2391-2398页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108912149A (en) | 2018-11-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108912149B (en) | Copper compound with 2-acetyl-3-ethylpyrazine thiosemicarbazone as ligand and synthetic method and application thereof | |
| CN105237563A (en) | 2-oxo propionic acid p-hydroxy benzoyl hydrazone bis(2,4-dichlorobenzyl) tin complex and preparation method and application thereof | |
| CN107629089A (en) | Tacrine platinum (II) complex of high activity and its synthetic method and application | |
| CN110950914A (en) | Iridium complex and synthesis method and application thereof | |
| CN109908364B (en) | Synthetic method and application of gold (III) metal complex with human serum albumin as carrier | |
| CN110772506A (en) | Application of benzil hydrazone-1-naphthaldehyde Schiff base | |
| CN107286220B (en) | 1,2, 4-triazole coupled dihydromyricetin derivative and preparation method and application thereof | |
| CN107573318A (en) | A kind of new gossypol Schiff bases derivative and its synthetic method for having antitumor activity | |
| CN111138372A (en) | Preparation and application of acetylpyrazine thiosemicarbazone metal chelating agent and metal complex thereof | |
| CN107200731B (en) | Thiazole ring-containing pyridone derivative and preparation method and application thereof | |
| CN107501303B (en) | Copper (II) complex and its synthetic method and application that a kind of brufen and quinoline-8-formaldehyde schiff bases are constructed | |
| CN113735781B (en) | Copper complex and preparation method and application thereof | |
| CN108148080B (en) | Organic golden (III) complex of metal and its synthetic method and application | |
| CN109627210B (en) | Gallium fluorescent probe, preparation method, application and application product thereof | |
| CN111116616B (en) | Preparation method and application of Schiff base complex of zinc | |
| CN110092789B (en) | Indolo [2,3-b ] carbazole derivative and application thereof | |
| CN110483465B (en) | Synthesis method of genistein bridged piperazine derivatives and application of genistein bridged piperazine derivatives in anti-tumor direction | |
| CN107382944B (en) | Coumarin gossypol derivatives with anti-tumor activity and synthesis method thereof | |
| CN110128334B (en) | Six-coordination nickel metal complex and synthesis method and application thereof | |
| CN112225733B (en) | Preparation method of 1,3, 4-thiadiazole pyridine-2-ketone derivative and application of derivative as anti-cancer drug | |
| CN111153855A (en) | Quinoline formaldehyde thiosemicarbazone ligand and synthetic method and application of copper complex thereof | |
| CN113234028B (en) | 5-fluorouracil and sarcosine cocrystal and preparation method and application thereof | |
| CN110698382B (en) | Application of benzil hydrazone-3-indole formaldehyde Schiff base | |
| CN114502550B (en) | Tegafur co-crystal | |
| CN110128333B (en) | Cu metal complex and synthetic method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20201222 Termination date: 20210625 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |