CN105820180A - Preparation and biological activity of pyrazolone thiophene hydrazide copper complex - Google Patents
Preparation and biological activity of pyrazolone thiophene hydrazide copper complex Download PDFInfo
- Publication number
- CN105820180A CN105820180A CN201610235905.6A CN201610235905A CN105820180A CN 105820180 A CN105820180 A CN 105820180A CN 201610235905 A CN201610235905 A CN 201610235905A CN 105820180 A CN105820180 A CN 105820180A
- Authority
- CN
- China
- Prior art keywords
- copper complex
- pyrazolone
- thiophene
- cell
- complex
- 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.)
- Pending
Links
- 150000004699 copper complex Chemical class 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 230000004071 biological effect Effects 0.000 title claims abstract description 4
- RFWSURBTVAWZHP-UHFFFAOYSA-N N1=NC(C=C1)=O.S1C=CC=C1 Chemical compound N1=NC(C=C1)=O.S1C=CC=C1 RFWSURBTVAWZHP-UHFFFAOYSA-N 0.000 title 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims abstract description 18
- 230000006907 apoptotic process Effects 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 11
- 239000010949 copper Substances 0.000 claims abstract description 9
- 230000000259 anti-tumor effect Effects 0.000 claims abstract description 6
- 230000004663 cell proliferation Effects 0.000 claims abstract description 6
- 230000001939 inductive effect Effects 0.000 claims abstract description 6
- 239000003446 ligand Substances 0.000 claims abstract description 6
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical group O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229930192474 thiophene Natural products 0.000 claims abstract description 5
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 claims description 10
- 239000013078 crystal Substances 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 229910052802 copper Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 238000011319 anticancer therapy Methods 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 229940000406 drug candidate Drugs 0.000 claims description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims 1
- 238000002050 diffraction method Methods 0.000 claims 1
- 150000002500 ions Chemical class 0.000 claims 1
- 230000001629 suppression Effects 0.000 claims 1
- 230000022131 cell cycle Effects 0.000 abstract description 6
- 238000002474 experimental method Methods 0.000 abstract description 5
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- 230000018199 S phase Effects 0.000 abstract description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract description 4
- 239000002246 antineoplastic agent Substances 0.000 abstract description 2
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 2
- 230000001472 cytotoxic effect Effects 0.000 abstract description 2
- 125000004430 oxygen atom Chemical group O* 0.000 abstract description 2
- 229910052757 nitrogen Inorganic materials 0.000 abstract 2
- LCKCXYAZSQCCHU-UHFFFAOYSA-N 3-methyl-2-(1,3-thiazol-2-yl)-1,3-thiazol-3-ium Chemical compound C[N+]1=C(SC=C1)C=1SC=CN=1 LCKCXYAZSQCCHU-UHFFFAOYSA-N 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 150000001875 compounds Chemical class 0.000 description 11
- 230000000694 effects Effects 0.000 description 9
- 239000003814 drug Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000001640 apoptogenic effect Effects 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000004043 dyeing Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- -1 Schiff base transition metal Chemical class 0.000 description 3
- 230000001093 anti-cancer Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- INAAIJLSXJJHOZ-UHFFFAOYSA-N pibenzimol Chemical compound C1CN(C)CCN1C1=CC=C(N=C(N2)C=3C=C4NC(=NC4=CC=3)C=3C=CC(O)=CC=3)C2=C1 INAAIJLSXJJHOZ-UHFFFAOYSA-N 0.000 description 3
- 108090000672 Annexin A5 Proteins 0.000 description 2
- 102000004121 Annexin A5 Human genes 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 239000002262 Schiff base Substances 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 235000021384 green leafy vegetables Nutrition 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 208000012639 Balance disease Diseases 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 108010040476 FITC-annexin A5 Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 190000008236 carboplatin Chemical compound 0.000 description 1
- 239000012930 cell culture fluid Substances 0.000 description 1
- 230000025084 cell cycle arrest Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 230000002508 compound effect Effects 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 239000012531 culture fluid Substances 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 231100000880 dysequilibrium Toxicity 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000012757 fluorescence staining Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000007952 growth promoter Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 210000000633 nuclear envelope Anatomy 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- SOGBOGBTIKMGFS-UHFFFAOYSA-N thiophene-2-carbohydrazide Chemical compound NNC(=O)C1=CC=CS1 SOGBOGBTIKMGFS-UHFFFAOYSA-N 0.000 description 1
- 230000001550 time effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
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 Table
- C07F1/005—Compounds containing elements of Groups 1 or 11 of the Periodic Table without C-Metal linkages
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to preparation and biological activity of a 4-acyl-pyrazolone thiophene hydrazide copper complex. The hexanuclear copper complex with a six-membered ring structure is prepared through a solution method; the structural formula of the copper complex is [Cu6L6] (ligand H2L=1-phenyl-3-methyl-4-propionyl-5-pyrazolone 2-thiophene hydrazide); in the asymmetric unit, Cu (II) is subjected to coordination with two oxygen atoms and a nitrogen atom of a ligand and a nitrogen atom on an adjacent ligand pyrazolone ring to form a coordination environment of CuN2O2. Proved by MTT (Methyl Thiazolyl Thiazolium) cytotoxic activity experiments and cell apoptosis experiments, the complex has a very good antitumor activity and is capable of inhibiting HeLa cellproliferation, inducing cell apoptosis and retaining the cell cycle at S phase, therefore, the complex can be used for preparing anti-cancer drugs.
Description
Technical field
The present invention discloses a kind of 4-acyl group pyrazolone-shrinking thiophene hydrazides and closes preparation and the application of copper complex.
Background technology
Since Rosenberg in 1969 finds that cisplatin has active anticancer, various new antitumoral metal complexs are synthesized in succession, such as novel platinum complex (carboplatin, oxaliplatin etc.), organotin complex, Schiff base transition metal complex etc., and progressively put into clinical practice.Wherein, Schiff's base and coordination compound thereof have the performance of excellence in the many-side such as antibacterial, antiviral, antitumor.And pyrazoline ketone Schiff's base is one of branch important in huge Schiff's base family.Wherein the antitumor action of 4-acyl group pyrazolone schiff base metal complex is increasingly subject to pay attention to.Metal complex after having the pyrazolone derivative of powerful rhetorical function and chelating with it has very abundant structure and more effective pharmaceutically active so that it is be likely to become efficient Clinical practice medicine.
These coordination compounds mainly play antitumaous effect by inducing cell apoptosis, and its effect has close ties with the ability of its inducing cell apoptosis.Apoptosis is the process that cell is the most dead, is the programmed cell death occurred by the respective cells of gene mediated.The dynamic equilibrium of cell proliferation and apoptosis is that multicellular organism maintains biological process most basic necessary to its Stability Analysis of Structures, interior environment function balance and growth promoter.And occurring of tumor may be precisely due to the dysequilibrium of cell proliferation and apoptosis causes.In coordination compound enters cell, generate the mixed complex of drug-metal-enzyme with the minor metallic element in cell thus and stop the duplication of virus.Meanwhile, some nucleic acid and protein are again good ligands, can have an effect with the metal ion dissociating out from coordination compound, make the functional group of some activity inactivate, therefore have obvious cytotoxic activity.Have it is experimentally confirmed that pyrazolone metal complex can induce the apoptosis of the KBv200 cell of cancerous cell and multidrug resistance at the bottom of human osteosarcoma HOS cell, HeLa Cells and population.
The present invention is condensed 2-thenoyl hydrazine on the basis of 4-acyl group pyrazolone; synthesis 4-acyl group pyrazolone Schiff's base 1-phenyl-3-methyl-4-propiono-5-pyrazolone-shrinking 2-thiophene hydrazides; as part; synthesize a kind of new complexes 1-phenyl-3-methyl-4-propiono-5-pyrazolone-shrinking 2-thiophene hydrazides and close copper; this coordination compound has fine anti-tumor activity; HeLa cell proliferation, and inducing cell apoptosis can be suppressed.The most described six-core copper complex is the drug candidate of a potential anticancer therapy.
Summary of the invention
It is an object of the invention to provide a class new complexes 1-phenyl-3-methyl-4-propiono-5-pyrazolone-shrinking 2-thiophene hydrazides and close copper and preparation method thereof and as anti-tumor drug.Use the solution synthetic method of routine, available six-core copper complex.This coordination compound can suppress HeLa cell proliferation, and inducing cell apoptosis, has preferable active anticancer.
The structural formula of the six-core copper complex that the present invention provides is respectively [Cu6L6].Part H2L is 1-phenyl-3-methyl-4-propiono-5-pyrazolone-shrinking 2-thiophene hydrazides.Described copper complex is lost two hydrions respectively from six parts and becomes L2-Afterwards with six metal one six-membered cyclic structures of composition.In its asymmetric cell, Cu (II) is coordinated with a nitrogen-atoms on two oxygen atoms of a part, a nitrogen-atoms and adjacent ligand pyrazole ring, forms the coordination environment of CuN2O2.
The preparation method of the six-core copper complex that the present invention provides comprises the steps:
The synthesis of step A(part): the ethanol solution of 2-thiophene hydrazides is under agitation slowly dropped to dissolved with in the hot ethanol solution of the 1-phenyl-3-methyl-4-propiono-5-pyrazolone of equimolar amounts, drips appropriate glacial acetic acid.Being stirred at reflux 4 h, stand cooling, sucking filtration, ethanol is washed, and obtains product as yellow powder.
The synthesis of step B(coordination compound): weigh above-mentioned part 0.05 g in beaker, add 10 mL ethanol and be allowed to dissolve, then drip the ethanol solution of 5 mL Schweinfurt greens (0.0282 g) wherein.2 hs being stirred at room temperature, separates out bulk crystals through slowly volatilization, filtration washing is dried obtains pure coordination compound.
Show that described six-core copper complex, to having good inhibiting effect to HeLa Cells, and has concentration dependent through MTT experiment.
Tested by Hoechst 33258 fluorescence staining and transmission electron microscope laboratory observation finds that described six-core copper complex makes karyopyknosis, find intracellular apoptotic body occurs.The double dye method flow cytomery result of Annexin-V/PI shows, after described six-core copper complex processes HeLa cell, cell cycle is arrested in the S phase.
In a word, the six-core copper complex cancerous cell that the present invention provides has preferable active anticancer.Preparation method of the present invention is simple, reliably.
Accompanying drawing explanation
Fig. 1 is copper complex crystal structure figure.
Fig. 2 is that copper complex is to HeLa cells in vitro antiproliferative effect.
Fig. 3 is the copper complex Morphology Effects to HeLa cell.
Fig. 4 is the early apoptosis effect of flow cytomery copper complex induction HeLa cell.
Fig. 5 is that copper complex processes cell cycle distribution after HeLa cell.
Detailed description of the invention
Illustrated embodiment below in conjunction with the accompanying drawings, the invention will be further described.
Embodiment 1: part H2The synthesis of L.
The ethanol solution of 2-thiophene hydrazides is under agitation slowly dropped to dissolved with in the hot ethanol solution of the 1-phenyl-3-methyl-4-propiono-5-pyrazolone of equimolar amounts, drips appropriate glacial acetic acid.Being stirred at reflux 4 h, stand cooling, sucking filtration, ethanol is washed, and obtains product as yellow powder.C18H18N4O2S(molecular weight: 354.12).Elementary analysis experiment value (theoretical value %): C 60.94(61.31)；H 5.08(5.11)；N 15.80(15.46)；S 9.02(8.89).
Embodiment 2: the synthesis of copper complex.
Weigh above-mentioned part 0.05 g in beaker, add 10 mL ethanol and be allowed to dissolve, then drip the ethanol solution of 5 mL Schweinfurt greens (0.0282 g) wherein.2 hs being stirred at room temperature, separates out bulk crystals through slowly volatilization, filtration washing is dried obtains pure coordination compound.(Fig. 1) and elementary analysis is analyzed, it was demonstrated that this crystal is [Cu by X-ray single crystal diffractometer6L6]。C108H102N24O12S6Cu6(molecular weight: 2501.86).Elementary analysis experiment value (theoretical value %): C 51.80(51.86)；H 4.08(4.11)；N 13.43(13.40) S 7.67(7.69).
Embodiment 3: the dependence test of the six-core copper complex that embodiment 2 obtains and test.
One, cytoactive detection: trophophase HeLa cell of taking the logarithm, with 1 × 105Individual cell/mL is inoculated in 96 well culture plates, and every hole is loaded 90 μ L.Being separately added into 10 μ L variable concentrations compounds after cultivating 24 h, after continuing to cultivate the corresponding time respectively, lucifuge adds 5 mg/mL
MTT every hole 20 μ L, continues to hatch 4 h.Abandon supernatant, add 100 μ L DMSO, after complete molten colour developing, measure OD value at 540/655 nm by microplate reader.Inhibitory rate of cell growth (%)=[1-(medicine group OD value-blank group OD value)/(control group OD value-blank group OD value)] × 100%, utilize statistical software prism calculation of half inhibitory concentration IC50Value.
Experimental result: as in figure 2 it is shown, after compound effects HeLa cell 72 h, described six-core copper complex has concentration dependent, half cytostatic concentration IC after effect HeLa cell 72 h to the inhibitory action of HeLa cell50Value is 1.287 μ g/mL, compared with blank group significant difference (P< 0.01), and (IC compared with positive drug cisplatin DDP effect group50=15.24 μ g/mL) also have significant difference (P< 0.05).Result shows, this six-core copper complex has significant In Vitro Anti proliferation function to HeLa cell.
Two, Hoechst 33258 dyeing is observed: be placed in by sterile cover slips in six orifice plates, drips culture fluid and makes it fit with bottom surface, and adding concentration is 1 × 105Individual/mL
HeLa cell 2 mL, adherent after be separately added into variable concentrations compound incubation 24 h, take out coverslip, PBS washes twice.Adding Hoechst 33258 dyeing liquor 0.5 mL of 0.5 μ g/mL, lucifuge dyes 5 min, and PBS washes twice.Take out coverslip, coverslip is posted a cover of cell on microscope slide, moisten fluorescence microscopy after cell with cell culture fluid.
Experimental result: as it is shown on figure 3, after six-core copper complex processes HeLa cell 24 h, light Microscopic observation finds along with the increase of drug level, attached cell quantity is gradually reducing.Fluorescence microscopy Microscopic observation finds that cell presents the distinctive dyeing property of apoptotic cell cell, and caryoplasm ratio increases, and nuclear matter is fine and close, while combine in nuclear membrane, has the appearance of apoptotic body.And cellular control unit core is uniform fluorescence.It has been observed that the karyopyknosis processed through six-core copper complex under transmission electron microscope, nucleocytoplasmic ratio reduces, and nuclei dyeing chromaticness condenses, nuclear matter marginalisation.And cellular control unit nuclear morphology is regular, structural integrity, kernel is clear, and chromatin and Cytoplasm are uniform.
Three, early apoptosis of cells rate and cell cycle distribution detection: after described six-core copper complex is respectively with variable concentrations and time effect HeLa cell, press Annexin V-FITC/PI apoptosis kit test kit description and Cell cycle strain solution respectively
Cell cycle detection kit description operates.Detect with flow cytometer (U.S. company BD).
Experimental result: Annexin-V/PI is double contaminates result as shown in Figure 4,6 μ g/mL
After six-core copper complex processes HeLa cell 24 h, early apoptosis of cells rate is 15.13 ± 0.78%, there were significant differences compared with matched group 2.37 ± 0.21% (P< 0.01).Six-core copper complex induction HeLa early apoptosis of cells has drug dose dependency.
After six-core copper complex processes HeLa cell 24 h, along with the increase of drug level, the cell of Sub-G1 phase gradually increases.6μg/mL
After six-core copper complex processes HeLa cell 24 h, progressively increased to 20.54%(Fig. 5 by the 3.28% of control group), after six-core copper complex process HeLa cell is described, the ratio of viable apoptotic cell is gradually increasing.It has also been found that the ratio of S phase cell also increases with the increase of medicine activity, progressively increased to 33.85% by the 25.32% of control group, there were significant differences compared with matched group (P< 0.05), this result explanation six-core copper complex can be by HeLa cell cycle arrest in the S phase.
Claims (4)
1. the present invention discloses a kind of 4-acyl group pyrazolone-shrinking thiophene hydrazides and closes preparation and the biological activity of copper complex, and its structural formula is [Cu6L6] (part H2L=1-phenyl-3-methyl-4-propiono-5-pyrazolone-shrinking 2-thiophene hydrazides), there is six-membered cyclic structure.
2. the copper complex described in claim 1 is to be prepared through method is stirred at room temperature by the metallic copper acetate of a certain amount of 4-acyl group pyrazolone-shrinking thiophene hydrazide ligands with equimolar ratio.
Copper complex the most according to claim 1, detected by X-ray single crystal diffraction method, it is characterized in that described copper complex is by the ring that Cu atom is that main body forms, six Ni metal (II) ions define a center cavity by the summit being distributed in hexatomic ring that the atom N bridging on part pyrazolone ring is staggered up and down, and each Cu (II) atom is all in four-coordination N2O2 plane.
Copper complex the most according to claim 1 has fine anti-tumor activity, it is possible to suppression HeLa cell proliferation, and inducing cell apoptosis, the most described six-core copper complex is the drug candidate of a potential anticancer therapy.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610235905.6A CN105820180A (en) | 2016-04-14 | 2016-04-14 | Preparation and biological activity of pyrazolone thiophene hydrazide copper complex |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610235905.6A CN105820180A (en) | 2016-04-14 | 2016-04-14 | Preparation and biological activity of pyrazolone thiophene hydrazide copper complex |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105820180A true CN105820180A (en) | 2016-08-03 |
Family
ID=56526939
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610235905.6A Pending CN105820180A (en) | 2016-04-14 | 2016-04-14 | Preparation and biological activity of pyrazolone thiophene hydrazide copper complex |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105820180A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114085206A (en) * | 2021-11-21 | 2022-02-25 | 福州市第二医院（福建省福州中西医结合医院、福州市职业病医院） | 2, 5-thiophene-dimethyl acetal 2-amino-4-methylphenol Schiff base and preparation method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103896969A (en) * | 2014-03-19 | 2014-07-02 | 河南理工大学 | Method for synthesizing 4-methyl salicylacylhydrazone copper complex with antitumor activity |
-
2016
- 2016-04-14 CN CN201610235905.6A patent/CN105820180A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103896969A (en) * | 2014-03-19 | 2014-07-02 | 河南理工大学 | Method for synthesizing 4-methyl salicylacylhydrazone copper complex with antitumor activity |
Non-Patent Citations (2)
| Title |
|---|
| HE CHUAN-CHUAN等: "Synthesis, Crystal Structure and Biological Properties of One Zinc(II) Complex Based on 4-Acyl Pyrazolone Derivative", 《结构化学》 * |
| 许贯诚: "4-酰基吡唑啉酮缩醛、酰肼过渡金属配合物的合成、表征与结构", 《中国优秀硕士学位论文全文数据库 工程科技I辑》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114085206A (en) * | 2021-11-21 | 2022-02-25 | 福州市第二医院（福建省福州中西医结合医院、福州市职业病医院） | 2, 5-thiophene-dimethyl acetal 2-amino-4-methylphenol Schiff base and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Balachandran et al. | Nickel (II) bis (isatin thiosemicarbazone) complexes induced apoptosis through mitochondrial signaling pathway and G0/G1 cell cycle arrest in IM-9 cells | |
| You et al. | Matrine exerts hepatotoxic effects via the ROS‐dependent mitochondrial apoptosis pathway and inhibition of Nrf2‐mediated antioxidant response | |
| Sun et al. | Nitidine chloride induces apoptosis, cell cycle arrest, and synergistic cytotoxicity with doxorubicin in breast cancer cells | |
| Tan et al. | Molecular mechanisms of apoptosis and cell selectivity of zinc dithiocarbamates functionalized with hydroxyethyl substituents | |
| Song et al. | Piperlongumine induces apoptosis in human melanoma cells via reactive oxygen species mediated mitochondria disruption | |
| CN106565686A (en) | Tubulin inhibitor | |
| Yao et al. | Synthesis and antitumor activity evaluation of maleopimaric acid N-aryl imide atropisomers | |
| Chen et al. | Coronarin D induces reactive oxygen species-mediated cell death in human nasopharyngeal cancer cells through inhibition of p38 MAPK and activation of JNK | |
| Bisceglie et al. | Autophagy and apoptosis: studies on the effects of bisthiosemicarbazone copper (ii) complexes on p53 and p53-null tumour cell lines | |
| Boskabadi et al. | The green-synthesized zinc oxide nanoparticle as a novel natural apoptosis inducer in human breast (MCF7 and MDA-MB231) and colon (HT-29) cancer cells | |
| CN108774270A (en) | Target Sorafenib anti-tumor platinum (II) complex and the preparation method and application thereof of human lung cancer mdr cell | |
| Chen et al. | Liriodenine induces G1/S cell cycle arrest in human colon cancer cells via nitric oxide-and p53-mediated pathway | |
| Guo et al. | Panaxydol inhibits the proliferation and induces the differentiation of human hepatocarcinoma cell line HepG2 | |
| Bostancıoğlu et al. | Novel ferrocenyl-containing N-acetyl-2-pyrazolines inhibit in vitro angiogenesis and human lung cancer growth by interfering with F-actin stress fiber polimeryzation | |
| Zhao et al. | The induction of apoptosis and autophagy in human hepatoma SMMC-7721 cells by combined treatment with vitamin C and polysaccharides extracted from Grifola frondosa | |
| Chen et al. | Biological evaluation of selected flavonoids as inhibitors of MNKs targeting acute myeloid leukemia | |
| Kacsir et al. | Reactive oxygen species production is responsible for antineoplastic activity of osmium, ruthenium, iridium and rhodium half-sandwich type complexes with bidentate glycosyl heterocyclic ligands in various cancer cell models | |
| Hussain et al. | Stevenleaf from Gynostemma Pentaphyllum inhibits human hepatoma cell (HepG2) through cell cycle arrest and apoptotic induction | |
| Wu et al. | HuaChanSu suppresses tumor growth and interferes with glucose metabolism in hepatocellular carcinoma cells by restraining Hexokinase-2 | |
| CN105820180A (en) | Preparation and biological activity of pyrazolone thiophene hydrazide copper complex | |
| Markowicz-Piasecka et al. | Sulfonamide metformin derivatives induce mitochondrial-associated apoptosis and cell cycle arrest in breast cancer cells | |
| He et al. | The protective effect of nitronyl nitroxide radical on peroxidation of A549 cell damaged by iron overload | |
| Chidambaram et al. | Synthesis, characterization, and evaluation of Cd [L-proline] 2, a novel histone deacetylase inhibitor that induces epigenetic modification of histone deacetylase isoforms in A549 cells | |
| Khan et al. | The role of mitochondrial dysfunction in cytotoxic effects of Solanum nigrum water extract on MCF-7 and MDA-MB-231 breast cancer cells | |
| Wu et al. | Dimethyltin (IV) and palladium (II) complexes derived from 2-benzoylpyridine N (4)-cyclohexylthiosemicarbazone: Synthesis, crystal structures and biological evaluation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160803 |
|
| WD01 | Invention patent application deemed withdrawn after publication |