CN107488151B - It is a kind of for detecting the compound and preparation method thereof and product of copper ion or preparation prevention and treatment Alzheimer disease drug - Google Patents
It is a kind of for detecting the compound and preparation method thereof and product of copper ion or preparation prevention and treatment Alzheimer disease drug Download PDFInfo
- Publication number
- CN107488151B CN107488151B CN201710752415.8A CN201710752415A CN107488151B CN 107488151 B CN107488151 B CN 107488151B CN 201710752415 A CN201710752415 A CN 201710752415A CN 107488151 B CN107488151 B CN 107488151B
- Authority
- CN
- China
- Prior art keywords
- copper ion
- formula
- formulas
- preparation
- compound
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Pathology (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Plasma & Fusion (AREA)
- Optics & Photonics (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
The present invention relates to field of biotechnology, in particular to a kind of compound for detecting copper ion and preparation prevention and treatment Alzheimer disease drug and preparation method thereof and product.The structural formula of the compound is as shown in Formulas I or Formula II.Using raw material that is cheap, being easy to get product can be obtained by one-step synthesis, reaction condition is mild, simple in two kinds of compounds of the invention；Have to copper ion highly selective, detection limit, can the variation of Sensitive Detection intracellular copper ion level up to nanomole grade；Ligand can chelate copper ion simultaneously, effectively inhibit the crosslinking of the beta-amyloid protein of copper ion induction, significantly reduce neurotoxicity caused by beta-amyloid protein is crosslinked, and have important potential value in Alzheimer disease drugs research and development field.
Description
Technical field
It is the present invention relates to field of biotechnology, in particular to a kind of for detecting copper ion or preparation prevention and treatment Alzheimer
Compound of disease drug and preparation method thereof and product.
Background technique
Copper ion is a kind of microelement necessary to human body higher organs, is closed in many important physiology courses such as neurotransmitter
At playing an important role in being synthesized with metabolism, anti-oxidative defense, cellular respiration, bone.The metabolic disorder and alzheimer ' of copper ion
The generation of the diseases such as silent disease, Parkinson's disease, Wei Ersenshi disease, fatty liver, diabetes is closely related.Such as Alzheimer's disease,
The copper ion of patient's brain higher concentration is to lead to one of beta-amyloid protein crosslinking and key factor of oxidation.Copper ion detection
The research of reagent and chelating agent is of great significance to the early diagnosis and treatment of disease.
At present the detection method of copper ion have atomic absorption spectrum, inductive coupling atomic emission spectrum, inductive coupling etc. from
Daughter mass spectrum, electrochemical method, fluorescence spectrum etc..In numerous methods, fluorescence spectrum is as a kind of sensitive, quick, high-throughput
Method be considered as optimal selection.There are many copper ion fluorescence probes to report at present, such as Hongping Zhou report
Fluorescence off-on probe (Sensors and Actuators B 206 (2015) 640) based on triphenylamine skeleton,
C.Huang, T.Kaur, Org etc. report rhodamine (Chem-Eur.J 14 (2008) 6892；Org Lett 14(2012)
14 406), and C.J.Fahrni etc. reports crown ether-like (Proc.Natl.Acad.Sci 102 (2005) 11179).These probes
Alternative identification copper ion, and can be used for external and intracellular copper ion detection, but the disadvantage is that synthesis step is complicated,
And detection limit is mostly micromole.Copper ion probe current simultaneously only has copper ion identification function, and can remove simultaneously
Copper ion inhibits not having been reported that also for beta-amyloid protein (Amyloid β, A β) crosslinking.
Summary of the invention
In view of this, the present invention provides a kind of for detecting the change of copper ion or preparation prevention and treatment Alzheimer disease drug
Close object and preparation method thereof and product.Two kinds of compounds (saline ligand) that the present invention reports utilize original that is cheap, being easy to get
Product can be obtained by one-step synthesis in material, and reaction condition is mild, simple.Ligand has highly selective, detection limit to copper ion
It spends up to nanomole grade, it can the variation of Sensitive Detection intracellular copper ion level.Ligand can chelate copper ion simultaneously, effectively inhibit
The crosslinking of the beta-amyloid protein of copper ion induction significantly reduces neurotoxicity caused by beta-amyloid protein is crosslinked, in A Er
Ci Haimo medicine, which researches and develops field, has important potential value.
In order to achieve the above-mentioned object of the invention, the present invention the following technical schemes are provided:
The present invention provides compound shown in a kind of Formulas I or Formula II, the structural formula of compound shown in Formulas I or Formula II is as follows:
The present invention also provides compounds shown in Formulas I or Formula II to prepare the application in copper ion detection kit.
Existing copper ion fluorescence probe synthesis step is complicated, and detection limit is mostly micromole's grade.What the present invention reported
Using raw material that is cheap, being easy to get product can be obtained by one-step synthesis, reaction condition is mild, simple in two kinds of saline ligands
It is single.Ligand have to copper ion it is highly selective, detection limit up to nanomole grade, can Sensitive Detection intracellular copper ion level become
Change.
The present invention also provides application of the compound shown in Formulas I or Formula II in preparation prevention and treatment Alzheimer disease drug.
The beta-amyloid protein crosslinking that existing copper ion fluorescence probe cannot inhibit copper ion to induce.The present invention report two
Kind ligand can chelate copper ion, effectively inhibit the crosslinking of the beta-amyloid protein of copper ion induction, significantly reduce beta amyloid
Neurotoxicity caused by protein-crosslinking.
The present invention also provides a kind of preparation methods of compound shown in Formulas I, and by 2- imidazole formaldehyde and 1,2- phenylenediamine exists
It is reacted in organic solvent, obtains compound shown in Formulas I.
The present invention also provides a kind of preparation methods of compound shown in Formula II, and by 4- imidazole formaldehyde and 1,2- phenylenediamine exists
It is reacted in organic solvent, obtains compound shown in Formula II.
Preferably, organic solvent is dehydrated alcohol.
Preferably, the temperature of reaction is 75 DEG C~78 DEG C, the time of reaction is 12~14h.
In embodiment provided by the invention, the temperature of reaction is 78 DEG C, and the time of reaction is 12h.
In specific embodiment provided by the invention, compound shown in Formulas I or Formula II the preparation method comprises the following steps: by 2- imidazoles first
Aldehyde or 4- imidazole formaldehyde dissolve by heating in dehydrated alcohol, and the ethanol solution containing 1,2- phenylenediamine, half an hour is added dropwise
It adds, mixed liquor back flow reaction 12h；It is precipitated, is filtered after reaction, solid is washed with dehydrated alcohol, anhydrous ether respectively
It washs, is dried in vacuo.
The present invention also provides a kind of copper ion detection kits, including compound shown in Formulas I and/or Formula II.
The present invention also provides a kind of methods of quickly detection copper ion, will contain compound shown in Formulas I and/or Formula II
Solution is mixed with sample to be tested, observes solution colour, and solution colour becomes green, then contains copper ion in sample to be tested.
In embodiment provided by the invention, the solution containing compound shown in Formulas I is mixed with sample to be tested, is observed molten
Liquid color, solution colour become yellow green, then contain copper ion in sample to be tested.
In embodiment provided by the invention, the solution containing compound shown in Formula II is mixed with sample to be tested, is observed
Solution colour, solution colour become light green color, then contain copper ion in sample to be tested.
Preferably, the composition of the solution containing compound shown in Formulas I and/or Formula II are as follows:
Compound shown in Formulas I and/or Formula II: 1~3mM；
DMSO:5~20% (v/v)；
Deionized water: it supplies.
In embodiment provided by the invention, the composition of the solution containing compound shown in Formulas I and/or Formula II are as follows:
Compound shown in Formulas I and/or Formula II: 1mM；
DMSO:10% (v/v)；
Deionized water: it supplies.
In quickly detection copper ion method (colorimetric method) of the invention, the detection of copper ion is limited to 1mM.
The present invention also provides a kind of methods of fluorescence detection copper ion, will contain compound shown in Formulas I and/or Formula II
Solution is mixed with sample to be tested, detects the fluorescence intensity change of solution, and the fluorescence intensity of solution reduces, then contains in sample to be tested
Copper ion.
In fluorescence detection copper ion method of the present invention, the detection of copper ion is limited to 10~40nM.
In the present invention, the copper ion detection of compound shown in Formulas I is limited to 10nM.
In the present invention, the copper ion detection of compound shown in Formula II is limited to 40nM.
In the present invention, the maximum excitation wavelength of fluorescence detection be 290~300nm, maximum emission wavelength be 340~
360nm。
In embodiment provided by the invention, maximum excitation wavelength when detecting the fluorescence intensity of compound shown in Formulas I is
297nm, maximum emission wavelength 356nm.
In embodiment provided by the invention, maximum excitation wavelength when detecting the fluorescence intensity of compound shown in Formula II is
297nm, maximum emission wavelength 345nm.
In embodiment provided by the invention, the solution containing compound shown in Formulas I is mixed with sample to be tested, is detected molten
The fluorescence intensity of the fluorescence intensity change of liquid, solution significantly reduces, then contains copper ion in sample to be tested.
In embodiment provided by the invention, the solution containing compound shown in Formula II is mixed with sample to be tested, is detected
The fluorescence of the fluorescence intensity change of solution, solution is quenched completely, then contains copper ion in sample to be tested.
The present invention also provides a kind of drugs, including compound shown in Formulas I and/or Formula II.
The present invention provides it is a kind of for detect copper ion or preparation prevention and treatment Alzheimer disease drug compound and its
Preparation method and product.The structural formula of the compound is as shown in Formulas I or Formula II.The present invention at least has one of following advantage:
1, two kinds of compounds of the invention (four tooth saline ligands) passes through one-step synthesis using raw material that is cheap, being easy to get
Product can be obtained, reaction condition is mild, simple.
2, two kinds of compound ligands of the invention have copper ion highly selective, and detection limit, can up to nanomole grade
The variation of Sensitive Detection intracellular copper ion level.
3, two kinds of compound ligands of the invention can chelate copper ion, effectively inhibit the beta amyloid egg of copper ion induction
White crosslinking significantly reduces neurotoxicity caused by beta-amyloid protein is crosslinked, and has in Alzheimer disease drugs research and development field
There is important potential value.
Detailed description of the invention
Fig. 1 shows ligand L 1, L2 colorimetric detection copper ion；
Fig. 2 shows 1 fluorescence detection copper ion of ligand L；
Fig. 3 shows 2 fluorescence detection copper ion of ligand L；
Fig. 4 shows ligand L 1, the variation of L2 fluorescence detection intracellular copper ion concentration；
Fig. 5 shows that SDS-PAGE electrophoretic analysis ligand inhibits the A β of copper ion induction to be crosslinked, [A β]=10 μM, [CuSO4]=5
μM, [L]=0-100 μM；Wherein 5-1 is electrophoretogram, and 5-2 is the histogram that 5-1 is drawn according to fluorescence intensity；
Fig. 6 shows MTT test U251 cell and A β, A β-CuCl2、Aβ-CuCl2- L is incubated for cell survival rate after 24 hours jointly
(Aβ:CuCl2: L=1:0.5:1, [A β]=10 μM).
Specific embodiment
The invention discloses it is a kind of for detect copper ion or preparation prevention and treatment Alzheimer disease drug compound and its
Preparation method and product, those skilled in the art can use for reference present disclosure, be suitably modified realization of process parameters.Especially need to refer to
Out, all similar substitutions and modifications are apparent to those skilled in the art, they be considered as include
In the present invention.Method and application of the invention is described by preferred embodiment, and related personnel can obviously not take off
Method described herein and application are modified or appropriate changes and combinations from the content of present invention, spirit and scope, come real
Now and using the technology of the present invention.
Provided by the present invention for the compound and its preparation of detection copper ion or preparation prevention and treatment Alzheimer disease drug
Raw materials used or auxiliary material, reagent are available on the market in method and product.
In the examples below, compound shown in Formulas I is defined as L1；Compound shown in Formula II is defined as L2.
Formulas I Chinese: (1- (1H- imidazoles -2-) methylamine of N, N'- (1,2- phenylene) two；
Formulas I English name: N, N'- (1,2-phenylene) bis (1- (1H-imidazol-2-yl) methanimine).
Formula II Chinese: (1- (1H- imidazoles -4-) methylamine of N, N'- (1,2- phenylene) two；
Formula II English name: N, N'- (1,2-phenylene) bis (1- (1H-imidazol-4-yl)
methanimine)。
Below with reference to embodiment, the present invention is further explained:
The synthesis of 1 L1 of embodiment
10mM (0.96g) 2- imidazole formaldehyde is dissolved by heating in the dehydrated alcohol of 10mL, 10mL is added dropwise dissolved with 5mM
The dehydrated alcohol of (0.54g) 1,2- phenylenediamine, solution colour gradually become yellow, and half an hour adds, and (78 DEG C) of mixed liquor are returned
Stream reaction 12h.A large amount of white precipitate is obtained after reaction, is filtered, solid uses dehydrated alcohol respectively, and anhydrous ether washs,
Vacuum drying, obtains white powdery solids, yield: 62.1%, ES-MS (C2H5OH):265.1([M+H]+).It reflects through structure
Fixed, the structure of ligand L 1 is shown in formula I:
The synthesis of 2 L2 of embodiment
10mM (0.96g) 4- imidazole formaldehyde is dissolved by heating in the dehydrated alcohol of 10mL, 10mL is added dropwise dissolved with 5mM
The dehydrated alcohol of (0.54g) 1,2- phenylenediamine, solution colour gradually become brown, and half an hour adds, and (78 DEG C) of mixed liquor are returned
Stream reaction 12h.A large amount of taupe precipitating is obtained after reaction, is filtered, solid uses dehydrated alcohol respectively, and anhydrous ether is washed
It washs, is dried in vacuo, obtains taupe crystallite, yield: 50.2%, ES-MS (C2H5OH):265.1([M+H]+).Through Structural Identification,
The structure of ligand L 2 is as shown in Formula II:
3 L1, L2 colorimetric detection copper ion of embodiment
Compound concentration is ligand solution (10%DMSO, the 90%H of 1mM2O), it is molten that different metal ions M is added dropwise into solution
Liquid (M=Li+、Na+、K+、Ca2+、Mg2+、Ba2+、Al3+、Cd2+、Co2+、Hg2+、Fe2+、Ni2+、Zn2+、Cu2+, 10%DMSO, 90%
H2O), observation solution colour variation, as shown in Figure 1, solution colour greening person (L1 becomes yellow green, and L2 becomes light green color) is
Copper ion, copper ion concentration are about 1mM.
4 L1 fluorescence detection copper ion of embodiment
Compound concentration is L1 solution (10%DMSO, the 90%H of 10nM2O), solution fluorescence spectrum (λ is testedex=297nm,
λem=356nm), different metal ions M solution (M=Li is added dropwise into solution+、Na+、K+、Ca2+、Mg2+、Ba2+、Al3+、Cd2+、
Co2+、Hg2+、Fe2+、Ni2+、Zn2+、Cu2+, 10%DMSO, 90%H2O), as shown in Fig. 2, be added after L1 fluorescence significant decrease person
For copper ion, copper ion concentration is about 10nM.
5 L2 fluorescence detection copper ion of embodiment
Compound concentration is L2 solution (10%DMSO, the 90%H of 10nM2O), solution fluorescence spectrum (λ is testedex=297nm,
λem=345nm), different metal ions (M) solution (M=Li is added dropwise into solution+、Na+、K+、Ca2+、Mg2+、Ba2+、Al3+、Cd2 +、Co2+、Hg2+、Fe2+、Ni2+、Zn2+、Cu2+, 10%DMSO, 90%H2O), as shown in figure 3, L2 fluorescence is quenched completely after being added
Person is copper ion, and copper ion concentration is about 40nM.
6 L1, L2 fluorescence detection intracellular copper ion of embodiment is horizontal
Cell is laid in 96 well culture plates, the hole 4000-5000/, after being incubated for 24 hours in cell incubator, to culture medium
Middle addition various concentration Cu2+Solution makes 25 μM, 50 μM, 100 μM, 200 μM of copper ion concentration.After 37 DEG C are incubated for 24 hours, inhale
Culture solution is removed, the fresh medium containing 10 μM of L1/L2 is added, is incubated for 2 hours, is sucked culture solution, measure ligand under microplate reader
Fluorescence says that ligand can detecte cell as shown in figure 4, the fluorescence of ligand gradually decreases as intracellular copper ion concentration is higher
Interior copper ion concentration variation.
7 SDS-PAGE electrophoresis detection L1, L2 of embodiment inhibits the A β crosslinking ability of copper ion induction
Prepare A β, A β-CuCl2、Aβ-CuCl2Three groups of solution (A β: CuCl of-L2: L=1:0.5:1, [A β]=10 μM), 37
After DEG C being protected from light incubation 2 hours, the variation of SDS-PAGE electrophoretic analysis A beta monomers band.As shown in figure 5, A β is mono- after copper ion is added
The amount of body is substantially reduced, and is illustrated that copper ion can induce A β crosslinking, as the amount of the increase A beta monomers of ligand concentration gradually increases, is said
The A β crosslinking of copper ion induction can be effectively suppressed in bright ligand.
8 MTT of embodiment measures neurotoxicity caused by L1, L2 inhibit A β to be crosslinked
Cell is laid in 96 well culture plates, the hole 4000-5000/, after being incubated for 24 hours in cell incubator, is separately added into
Aβ、Aβ-CuCl2、Aβ-CuCl2- L solution (A β: CuCl2: L=1:0.5:1, [A β]=10 μM).After 37 DEG C are incubated for 24 hours, add
The MTT solution for entering 20 μ L 5mg/mL continues to be incubated for 4 hours, sucks culture solution, and 100 μ L DMSO, shaking table low speed concussion 5 is added
Minute, OD value at 579nm is measured under microplate reader, calculates cell survival rate, as shown in fig. 6, after being incubated for 24 hours jointly with A β, carefully
Born of the same parents' survival rate is 28%, and after copper ion is added, cell survival rate is only 5%, and cell survival rate increases to 45% after ligand is added
With 31%, illustrate that neurotoxicity caused by A β is crosslinked can be effectively suppressed in ligand.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (10)
1. compound shown in a kind of Formulas I or Formula II:
2. compound shown in Formulas I or Formula II is preparing copper ion detection kit or is preventing and treating answering in Alzheimer disease drug
With compound structure shown in Formulas I or Formula II is as follows:
3. a kind of preparation method of compound shown in Formulas I, which is characterized in that by 2- imidazole formaldehyde and 1,2- phenylenediamine is organic molten
It is reacted in agent, obtains compound shown in Formulas I；
4. a kind of preparation method of compound shown in Formula II, which is characterized in that by 4- imidazole formaldehyde and 1,2- phenylenediamine is organic
It is reacted in solvent, obtains compound shown in Formula II；
5. preparation method according to claim 3 or 4, which is characterized in that the organic solvent is dehydrated alcohol.
6. preparation method according to claim 3 or 4, which is characterized in that the temperature of the reaction is 75 DEG C~78 DEG C, instead
The time answered is 12~14h.
7. a kind of copper ion detection kit, which is characterized in that including compound shown in Formulas I and/or Formula II；
8. a kind of method for quickly detecting copper ion with non-treatment purpose, which is characterized in that will be containing shown in Formulas I and/or Formula II
The solution of compound is mixed with sample to be tested, observe solution colour, solution colour become green, then in sample to be tested containing copper from
Son；
9. a kind of method with non-treatment purpose fluorescence detection copper ion, which is characterized in that will be containing shown in Formulas I and/or Formula II
The solution of compound is mixed with sample to be tested, detects the fluorescence intensity change of solution, the fluorescence intensity of solution reduces, then to test sample
Contain copper ion in product；
10. a kind of drug, which is characterized in that including compound shown in Formulas I and/or Formula II；
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710752415.8A CN107488151B (en) | 2017-08-28 | 2017-08-28 | It is a kind of for detecting the compound and preparation method thereof and product of copper ion or preparation prevention and treatment Alzheimer disease drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710752415.8A CN107488151B (en) | 2017-08-28 | 2017-08-28 | It is a kind of for detecting the compound and preparation method thereof and product of copper ion or preparation prevention and treatment Alzheimer disease drug |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107488151A CN107488151A (en) | 2017-12-19 |
| CN107488151B true CN107488151B (en) | 2019-10-29 |
Family
ID=60646078
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710752415.8A Expired - Fee Related CN107488151B (en) | 2017-08-28 | 2017-08-28 | It is a kind of for detecting the compound and preparation method thereof and product of copper ion or preparation prevention and treatment Alzheimer disease drug |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107488151B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102374047B1 (en) | 2020-03-11 | 2022-03-15 | 한국과학기술원 | Composition for preventing, improving or treating Alzheimer's disease comprising N,N′-Diacetyl-p-phenylenediamine as an active ingredient |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109946280A (en) * | 2019-03-29 | 2019-06-28 | 南京工业大学 | Method for quantitatively detecting soluble β amyloid protein by using proportional metering type fluorescent probe |
| CN111808096B (en) * | 2020-06-30 | 2022-10-21 | 广东工业大学 | Novel ligand for copper ion detection, preparation thereof, novel ruthenium complex and near-infrared long-life fluorescent probe |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107043353A (en) * | 2016-11-16 | 2017-08-15 | 齐鲁工业大学 | A kind of imidazoles benzaldehyde-p-phenylenediamine bi-schiff base and preparation method thereof |
-
2017
- 2017-08-28 CN CN201710752415.8A patent/CN107488151B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107043353A (en) * | 2016-11-16 | 2017-08-15 | 齐鲁工业大学 | A kind of imidazoles benzaldehyde-p-phenylenediamine bi-schiff base and preparation method thereof |
Non-Patent Citations (8)
| Title |
|---|
| A benzimidazole-based fluorescent sensor for Cu2+ and its complex with a phosphate anion formed through a Cu2+ displacement approach;Preeti Saluja et al.;《Tetrahedron Letters》;20120421;第53卷(第26期);第3293页Figure 1A和第第3294页Scheme 2 * |
| Colorimetric and Fluorescent chemosensors for Cu2+. A comprehensive review from the year 2013-15;Duraisamy Udhayakumari et al.;《Analytical Methods》;20161205;第9卷(第4期);第552-578页 * |
| Cooperative Catalysis: Large Rate Enhancements with Bimetallic Rhodium Complexes;Sandra W. S. Choy et al.;《Organometallics》;20130816;第32卷(第17期);第4726-4729页 * |
| Fluorescence sensors for Cu2+ based on conjugated indole Schiff base;Juan Bu et al.;《Res Chem Intermed》;20130327;第40卷(第8期);第3119页Abstract，第3120页Scheme 1，第3121页第1段，第3124页最后1段至第3125页第1段，第3124页Fig.2a，第3125页Table 2 * |
| Schiff based fluorescence probes for Cu2+ based on imidazole and benzimidazole;Xingjian Wang et al.;《Sensors and Actuators B》;20150321;第214卷;第139页Scheme 1和第142页左栏第2段 * |
| Stable Eight-Coordinate Iron(III/II) Complexes;Ashis K. Patra et al.;《Inorg. Chem.》;20100128;第49卷(第5期);第2032-2034页 * |
| Structure and properties of an eight-coordinate Mn(II) complex that demonstrates a high water relaxivity;Koustubh S. Dube et al.;《Dalton Trans.》;20110624;第40卷(第29期);第7496-7498页 * |
| 基于Saline四齿配体的铜离子荧光探针及β-淀粉样蛋白交联抑制剂研究;于会娟等;《中国化学会第八届全国配位化学会议论文集—口头报告》;20170731;第30-31页 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102374047B1 (en) | 2020-03-11 | 2022-03-15 | 한국과학기술원 | Composition for preventing, improving or treating Alzheimer's disease comprising N,N′-Diacetyl-p-phenylenediamine as an active ingredient |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107488151A (en) | 2017-12-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Meng et al. | NBD-based fluorescent chemosensor for the selective quantification of copper and sulfide in an aqueous solution and living cells | |
| CN107488151B (en) | It is a kind of for detecting the compound and preparation method thereof and product of copper ion or preparation prevention and treatment Alzheimer disease drug | |
| Pan et al. | Monitoring NAD (P) H by an ultrasensitive fluorescent probe to reveal reductive stress induced by natural antioxidants in HepG2 cells under hypoxia | |
| Chen et al. | Wide-acidity-range pH fluorescence probes for evaluation of acidification in mitochondria and digestive tract mucosa | |
| JP4926382B2 (en) | Novel γ-butyrolactone compound and pharmaceutical composition thereof | |
| CN106083888B (en) | The fluorescence probe of hydrogen sulfide in a kind of detection cancer cell | |
| CN109054807B (en) | Double-organelle targeted nano probe and preparation and application thereof | |
| Megnin et al. | Studies on the mechanism of selective retention of porphyrins and metalloporphyrins by cancer cells | |
| Shao et al. | 3D two-photon brain imaging reveals dihydroartemisinin exerts antiepileptic effects by modulating iron homeostasis | |
| Son et al. | Phosphorescent ruthenium complexes with a nitroimidazole unit that image oxygen fluctuation in tumor tissue | |
| Lv et al. | Dual pH-triggered catalytic selective Mn clusters for cancer radiosensitization and radioprotection | |
| Wang et al. | Fluoride-specific fluorescence/MRI bimodal probe based on a gadolinium (III)–flavone complex: synthesis, mechanism and bioimaging application in vivo | |
| Gao et al. | Design, synthesis and biological evaluation of a novel Cu 2+-selective fluorescence sensor for bio-detection and chelation | |
| CN112159522A (en) | Water-soluble rhodamine-based fluorescent/colorimetric dual-mode probe and preparation method and application thereof | |
| Niu et al. | A bifunctional fluorescent sensor for CCCP-induced cancer cell apoptosis imaging | |
| CN112121182B (en) | Nano probe for detecting hypoxic cells and preparation method and application thereof | |
| CN113956292A (en) | Mitochondrial targeting compound with aggregation-induced emission property and synthesis method and application thereof | |
| Li et al. | Detection of nano Eu2O3 in cells and study of its biological effects | |
| CN110563684B (en) | Flavone gallium complex and synthetic method and application thereof | |
| CN113045599B (en) | Method for distinguishing cancer cells/tissues with high contrast and preparation of fluorescent probe | |
| CN109810113A (en) | A kind of alkaloid compound and the preparation method and application thereof | |
| CN109106956B (en) | Nano diagnosis and treatment agent and preparation method and application thereof | |
| KR102232979B1 (en) | A new compound of DO3A gadolinium complex, an anti-inflammatory and a contrast agent containing the same | |
| CN110818739B (en) | Metal iridium complex with synergistic response to tumor microenvironment pH/hypoxic and application thereof | |
| CN108440577B (en) | Mixed copper-based complex and preparation 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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20191029 Termination date: 20210828 |