CN110317234B - Preparation method and application of isonuclear high-activity polymer containing flutolanil phenanthroline ligand - Google Patents
Preparation method and application of isonuclear high-activity polymer containing flutolanil phenanthroline ligand Download PDFInfo
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- CN110317234B CN110317234B CN201910165228.9A CN201910165228A CN110317234B CN 110317234 B CN110317234 B CN 110317234B CN 201910165228 A CN201910165228 A CN 201910165228A CN 110317234 B CN110317234 B CN 110317234B
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- 239000003446 ligand Substances 0.000 title claims abstract description 29
- 229920000642 polymer Polymers 0.000 title claims abstract description 20
- 230000000694 effects Effects 0.000 title claims abstract description 18
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 239000005786 Flutolanil Substances 0.000 title description 2
- PTCGDEVVHUXTMP-UHFFFAOYSA-N flutolanil Chemical compound CC(C)OC1=CC=CC(NC(=O)C=2C(=CC=CC=2)C(F)(F)F)=C1 PTCGDEVVHUXTMP-UHFFFAOYSA-N 0.000 title description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 72
- 239000000243 solution Substances 0.000 claims abstract description 13
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910052802 copper Inorganic materials 0.000 claims abstract description 12
- 239000010949 copper Substances 0.000 claims abstract description 12
- 229910000570 Cupronickel Inorganic materials 0.000 claims abstract description 10
- YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 claims abstract description 10
- YOCUPQPZWBBYIX-UHFFFAOYSA-N copper nickel Chemical compound [Ni].[Cu] YOCUPQPZWBBYIX-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 10
- 239000013078 crystal Substances 0.000 claims abstract description 9
- 150000002815 nickel Chemical class 0.000 claims abstract description 9
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims abstract description 7
- 150000001408 amides Chemical class 0.000 claims abstract description 7
- 229940079593 drug Drugs 0.000 claims abstract description 7
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 7
- 239000011737 fluorine Substances 0.000 claims abstract description 7
- 239000000706 filtrate Substances 0.000 claims abstract description 6
- 238000001914 filtration Methods 0.000 claims abstract description 6
- 239000011259 mixed solution Substances 0.000 claims abstract description 6
- 238000010992 reflux Methods 0.000 claims abstract description 6
- ZLQBNKOPBDZKDP-UHFFFAOYSA-L nickel(2+);diperchlorate Chemical compound [Ni+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O ZLQBNKOPBDZKDP-UHFFFAOYSA-L 0.000 claims abstract description 5
- 206010009944 Colon cancer Diseases 0.000 claims description 5
- 208000029742 colonic neoplasm Diseases 0.000 claims description 5
- 208000005017 glioblastoma Diseases 0.000 claims description 5
- MDQRDWAGHRLBPA-UHFFFAOYSA-N fluoroamine Chemical class FN MDQRDWAGHRLBPA-UHFFFAOYSA-N 0.000 claims 1
- 230000002218 hypoglycaemic effect Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 19
- -1 difluoro oxamide bis-phenanthroline copper nickel Chemical compound 0.000 abstract description 11
- 239000002246 antineoplastic agent Substances 0.000 abstract description 7
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 7
- 229910021586 Nickel(II) chloride Inorganic materials 0.000 abstract description 4
- 230000001093 anti-cancer Effects 0.000 abstract description 4
- QMMRZOWCJAIUJA-UHFFFAOYSA-L nickel dichloride Chemical compound Cl[Ni]Cl QMMRZOWCJAIUJA-UHFFFAOYSA-L 0.000 abstract description 4
- 239000008280 blood Substances 0.000 abstract description 2
- 210000004369 blood Anatomy 0.000 abstract description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 abstract 2
- UQPSGBZICXWIAG-UHFFFAOYSA-L nickel(2+);dibromide;trihydrate Chemical compound O.O.O.Br[Ni]Br UQPSGBZICXWIAG-UHFFFAOYSA-L 0.000 abstract 1
- 229910052697 platinum Inorganic materials 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 13
- 102000002072 Non-Receptor Type 1 Protein Tyrosine Phosphatase Human genes 0.000 description 6
- 108010015847 Non-Receptor Type 1 Protein Tyrosine Phosphatase Proteins 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 229910021585 Nickel(II) bromide Inorganic materials 0.000 description 3
- 239000003472 antidiabetic agent Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 3
- IPLJNQFXJUCRNH-UHFFFAOYSA-L nickel(2+);dibromide Chemical compound [Ni+2].[Br-].[Br-] IPLJNQFXJUCRNH-UHFFFAOYSA-L 0.000 description 3
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 102000002727 Protein Tyrosine Phosphatase Human genes 0.000 description 1
- 235000005811 Viola adunca Nutrition 0.000 description 1
- 240000009038 Viola odorata Species 0.000 description 1
- 235000013487 Viola odorata Nutrition 0.000 description 1
- 235000002254 Viola papilionacea Nutrition 0.000 description 1
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
- 229940127003 anti-diabetic drug Drugs 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 208000016097 disease of metabolism Diseases 0.000 description 1
- KAKKHKRHCKCAGH-UHFFFAOYSA-L disodium;(4-nitrophenyl) phosphate;hexahydrate Chemical compound O.O.O.O.O.O.[Na+].[Na+].[O-][N+](=O)C1=CC=C(OP([O-])([O-])=O)C=C1 KAKKHKRHCKCAGH-UHFFFAOYSA-L 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000005389 magnetism Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000003801 protein tyrosine phosphatase 1B inhibitor Substances 0.000 description 1
- 108020000494 protein-tyrosine phosphatase Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 150000003623 transition metal compounds Chemical class 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/80—Polymers containing hetero atoms not provided for in groups A61K31/755 - A61K31/795
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/04—Nickel compounds
- C07F15/045—Nickel compounds without a metal-carbon linkage
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
- C08G83/008—Supramolecular polymers
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Polymers & Plastics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a high activity polymer containing fluorine amide phenanthroline copper nickel heteronuclear, a preparation method and application thereof, the structural formula is as follows,
Description
Technical Field
The invention relates to a preparation method of a high-activity polymer containing fluorine amide phenanthroline copper nickel, and application of the compound in preparing an anti-cancer medicament and an anti-diabetic medicament.
Background
Since the discovery of cisplatin, transition metal compounds with targeting functions to proteins and DNA have attracted attention in the field of anticancer drugs, among many bridging ligands, oxamide bridging ligand has been regarded as a multifunctional ligand, and has been paid attention to scientists by its unique bridging structure and its complex, however, the research on oxamide coordination compounds has been mostly focused on the fields of catalysis and molecular magnetism, and in recent years, more researchers have applied the oxamide coordination compounds to anticancer drugs.
Type II diabetes, an endocrine-disturbance metabolic disease, has become a third most serious chronic disease threatening human health after tumor and cardiovascular disease. In the existing research on hypoglycemic drugs, many reports are made on PTP1B inhibitors, but no report is made on the research on the PTP1B inhibitory activity of the compounds.
Disclosure of Invention
Aiming at the prior art, the invention provides a novel oxamide ligand copper-nickel bimetallic complex compound containing bromine atoms, and provides a preparation method and application of the compound.
In order to achieve the purpose, the invention adopts the following technical scheme:
a high-activity polymer containing fluorine amide phenanthroline copper nickel heteronuclear has the following structural formula:
a preparation method of a fluorine-containing amide phenanthroline copper-nickel heteronuclear high-activity polymer comprises the following steps:
dissolving 2.0-4.0mmol of oxamide mononuclear copper ligand in 10-20ml of methanol, dissolving 2.0-4.0mmol of nickel salt in 5-10ml of methanol, adding the dissolved nickel salt into the methanol solution of the mononuclear copper ligand, reacting for 1-3 hours at 60-100 ℃, then adding the methanol solution dissolved with 4.0-6.0mmol of 1, 10-phenanthroline ligand into the mixed solution of the ligands, refluxing for 5-12 hours at 60-100 ℃, filtering, slowly volatilizing the filtrate for 1 week to obtain blue blocky crystals, namely the difluoride oxamide diphenanthrene copper nickel heteronuclear polymer. The nickel salt is as follows: one or more of nickel perchlorate, nickel chloride, nickel bromide and the like.
The reaction equation is as follows:
the difluoride oxamide-containing copper-nickel phenanthroline heteronuclear polymer is applied to preparation of medicines for treating human glioblastoma cell A172 and human colon cancer cell LOVO.
The invention has the beneficial effect that the molecular formula of the difluoro oxamide phenanthroline copper nickel containing heteronuclear polymer is C38H30ClCuF2N7NiO8(ii) a Has molecular weight of 908.39 and high anticancer activity, and can be used as raw material for preparing medicines for treating human glioblastoma A172 and human colon cancer LOVO.
In addition, the compounds are found to have higher activity of reducing blood sugar for the first time. Compared with the currently commonly used similar drugs, the difluoro oxamide phenanthroline copper nickel containing heteronuclear polymer has the characteristics of high activity, low cost, simple preparation method and the like, and provides a new way for developing related drugs.
Detailed Description
The present invention will be further illustrated by the following examples, which are intended to be merely illustrative and not limitative.
Example 1:
dissolving 2mmol of oxamide mononuclear copper ligand in 10ml of methanol, dissolving 2mmol of nickel perchlorate in 10ml of methanol, adding the dissolved nickel perchlorate into a methanol solution of the mononuclear copper ligand, reacting for 1 hour at 60 ℃, then adding the methanol solution dissolved with 4mmol of 1 and 10-phenanthroline ligand into a mixed solution of the ligands, refluxing for 5 hours at 60 ℃, filtering, and slowly volatilizing the filtrate for 1 week to obtain a blue blocky crystal. Namely the difluoro oxamide bis-phenanthroline copper nickel heteronuclear polymer.
Infrared, elemental analysis and X-ray single crystal diffraction results:
infrared spectrum (KBr, cm-1) v (N-H)3416 v as (C ═ O) 16111567; v iss(C6H6-H) 1455 728
Elemental analysis: c, 50.24; h, 3.33; n, 10.79%. Found C, 50.22; h, 3.34; n,10.77 percent.
X-ray single crystal diffraction results:
molecular structural formula (ellipsoid probability is 50%)
Crystallographic data and structural analysis parameters for the compounds of Table 1
Example 2:
dissolving 3mmol of oxamide mononuclear copper ligand in 15ml of methanol, dissolving 3mmol of nickel chloride in 8ml of methanol, adding the dissolved nickel chloride into a methanol solution of the mononuclear copper ligand, reacting for 1 hour at 60 ℃, then adding the methanol solution dissolved with 5mmol of 1 and 10-phenanthroline ligand into a mixed solution of the ligand, refluxing for 5 hours at 60 ℃, filtering, and slowly volatilizing the filtrate for 1 week to obtain a blue blocky crystal. Namely the difluoro oxamide bis-phenanthroline copper nickel heteronuclear polymer.
Example 3:
dissolving 4mmol of oxamide mononuclear copper ligand in 20ml of methanol, dissolving 4mmol of nickel bromide in 10ml of methanol, adding the dissolved nickel bromide into a methanol solution of the mononuclear copper ligand, reacting for 1 hour at 60 ℃, then adding the methanol solution dissolved with 6mmol of 1 and 10-phenanthroline ligand into a mixed solution of the ligands, refluxing for 5 hours at 60 ℃, filtering, and slowly volatilizing the filtrate for 1 week to obtain a blue blocky crystal. Namely the difluoro oxamide bis-phenanthroline copper nickel heteronuclear polymer.
Test example:
the determination of the in vitro anticancer activity of the difluoride oxamide phenanthroline copper-nickel contained heteronuclear polymer is realized by an MTT experimental method, and the principle is as follows: based on the metabolic reduction of exogenous MTT (3- (4, 5-dimethylthiozol-2-yl) -2, 5-diphenylterazolium bromide), NADP-related dehydrogenase was present in mitochondria of living cells, yellow MTT was reduced to insoluble blue-violet Formazan (Formazan), dead cells were not treated with this enzyme, MTT was not reduced, Formazan was dissolved in DMSO, and then the optical density at a characteristic wavelength (570nm wavelength) was measured with a microplate reader to process the data. The method can indirectly reflect the number of living cells. 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 screening of anti-tumor drugs, cytotoxicity test, tumor radiosensitivity determination and the like.
The results of analyzing human normal cells, human glioblastoma cell a172 and human colon cancer cell LOVO by MTT assay and determining IC50 values are shown in table 2, and the results are as follows: as can be seen from the data in the table, the anticancer drug of the present invention does not affect the growth of normal cells, but has high in vitro activity on human glioblastoma cell A172 and human colon cancer cell LOVO, and can be used as a candidate compound of anticancer drugs.
Table 2 in vitro activity test data of difluo-oxamide-containing phenanthroline copper nickel heteronuclear polymer anticancer drug
Application of bromine-containing oxamide copper-nickel heteronuclear compound in preparation of antidiabetic drugs
The compounds synthesized in the above examples were used as test compounds to test their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), and the specific test cases were as follows:
200. mu.L of the reaction system contained PTP1B (recombinant expression), buffer (25mM HEPES,50mM sodium chloride, 2.5mM EDTA, 0.1% BSA, pH 7.2) and the above compounds, while blank control (containing no enzyme and the above compounds) and negative control (containing no the above compounds) were set, reacted at 37 ℃ for 10min, protein tyrosine phosphatase substrate PNPP was added, reacted at 37 ℃ for 30min, 2M Na2CO3 was added to terminate the reaction, and OD was measured at 405 nm. The inhibition rate was calculated from the OD value, and ═ 1- (OD sample-OD blank)/(OD negative-OD blank) ] × 100%. During primary screening, double holes are arranged at single concentration of each sample, the IC50 value of the sample with the inhibition rate of more than 70 percent is determined, six concentrations are diluted by each sample in a gradient manner, and double holes are arranged at each concentration. IC50 was calculated from the inhibition using a 4Parameter Logistic Model in Xlfit software. The test results are shown in Table 3.
TABLE 3 data for the in vitro inhibitory Activity of the Compound PTP1B
| Sample IC50 | 5.63±0.17(μM) |
| Sodium orthovanadate | 6.84±0.79(μM) |
As can be seen from the activity results in Table 3, the compound of the present invention shows very good inhibitory activity against protein tyrosine phosphatase 1B, has an effect significantly superior to that of positive control sodium orthovanadate, and can be used for preparing a medicament for treating diabetes.
Although the present invention has been described with reference to the specific embodiments, it is not intended to limit the scope of the present invention, and various modifications and variations can be made by those skilled in the art without inventive changes based on the technical solution of the present invention.
Claims (3)
1. A high-activity polymer containing fluorine amide phenanthroline copper nickel heteronuclear is characterized in that the structural formula is as follows:
2. the preparation method of the high-activity polymer containing the fluorine-containing amide phenanthroline copper nickel heteronuclear according to claim 1, which is characterized by comprising the following steps: dissolving 2.0-4.0mmol of oxamide mononuclear copper ligand in 10-20ml of methanol, dissolving 2.0-4.0mmol of nickel salt in 5-10ml of methanol, adding the dissolved nickel salt into the methanol solution of the mononuclear copper ligand, reacting for 1-3 hours at 60-100 ℃, then adding the methanol solution dissolved with 4.0-6.0mmol of 1 and 10-phenanthroline ligand into the mixed solution, refluxing for 5-12 hours at 60-100 ℃, filtering, slowly volatilizing the filtrate for 1 week to obtain blue blocky crystals, namely the fluorine-containing amide phenanthroline copper-nickel heteronuclear high-activity polymer, wherein the nickel salt is nickel perchlorate.
3. The use of the high activity polymer of copper nickel isonuclear phenanthroline containing fluoro-amides according to claim 1 in the preparation of drugs for treating human glioblastoma cell a172 and human colon cancer cell LOVO, and in drugs with hypoglycemic activity.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102286057A (en) * | 2011-07-07 | 2011-12-21 | 北华大学 | Oleanane-type triterpenoid compounds and preparation method and medicinal use thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102286057A (en) * | 2011-07-07 | 2011-12-21 | 北华大学 | Oleanane-type triterpenoid compounds and preparation method and medicinal use thereof |
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