CN110066288A - A kind of naproxen copper complex and preparation method thereof with inhibition urease activity - Google Patents
A kind of naproxen copper complex and preparation method thereof with inhibition urease activity Download PDFInfo
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- CN110066288A CN110066288A CN201810086423.8A CN201810086423A CN110066288A CN 110066288 A CN110066288 A CN 110066288A CN 201810086423 A CN201810086423 A CN 201810086423A CN 110066288 A CN110066288 A CN 110066288A
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- naproxen
- complex
- urease activity
- copper
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic System
- C07F1/08—Copper compounds
Abstract
The invention discloses a kind of with the naproxen copper complex and preparation method thereof for inhibiting urease activity, belongs to complex synthesis and field of pharmaceutical chemistry technology.The present invention is with naproxen and 1, and 3- propane diamine, using solvent evaporation method, prepares the naproxen copper complex of mononuclear structure using copper ion as center ion for ligand.Complex disclosed by the invention has preferable bioactivity, it is found through detection, complex and positive control drug acetohydroxamic acid (N- hydroxyl acetamide) of the present invention is respectively as follows: 1.69,6.26 μm of ol/L about the IC50 value of inhibition urase, show to inhibit urease activity complex better than acetohydroxamic acid, complex reaches 72.6% to the inhibiting rate of urease activity, is a kind of preferable urease inhibitor.
Description
Technical field
The present invention relates to a kind of with the naproxen copper complex and its preparation method and application for inhibiting urease activity, belongs to
Complex synthesis and field of pharmaceutical chemistry technology.
Background technique
Naproxen is class I non-steroid anti-inflammatory agent, can be by inhibiting the synthesis of prostaglandin to play anti-inflammatory, antipyretic, analgesia
Effect, side effect show stomach and intestine adverse reaction, such as gastric ulcer, colonic pathological change.
Helicobacter pylori is a kind of gram-Negative bacillus, it can survive under the strong acidic environment of stomach, in addition to utilizing
Its helicoidal structure drills through the mucus of mucosa surface, colonizes in the relatively neutral ring in mucus close to gastric epithelial
Except in border, also have benefited from the high activity urase that itself contains.Urase is a kind of enzyme for hydrolyzing urea, it can decompose food
In urea generate ammonia, form protective layer and gastric acid around thallus and completely cut off, while neutralizing gastric acid, form alkaline microenvironment.
To sum up reason, to bury hidden danger for diseases such as gastritis, gastric ulcer, gastric cancers.Therefore, anti-to traditional non-steroidal
Scorching medicine is transformed, and exploitation is efficiently, side effect is low and being able to suppress the anti-inflammatory drug of urase, there is very important reality to anticipate
Justice.
Urase is very sensitive to metal ion, meanwhile, many metal complexs have good antibacterial, it is antitumor, anti-inflammatory,
Anti-oxidant isoreactivity.Therefore, the cooperation of synthesis non-steroidal anti-inflammatory drugs is reacted with metal ion with biologically active small molecule
Object is the effective means for reducing drug side-effect, improving pharmaceutical activity.
Summary of the invention
It is an object of that present invention to provide a kind of with the naproxen copper complex and preparation method thereof for inhibiting urease activity and
Purposes.
The present invention is using NSAID, naproxen as ligand, and with small molecule containing N 1,3- propane diamine is Ligands, with copper
Ionic reaction prepares complex and cultivates its monocrystalline.Mono-crystalline structures are characterized by X-ray diffractometer, and test Nabumetone
Raw and its complex inhibition urease activity.Naproxen does not inhibit urease activity, and complex of the invention is shown well
Inhibit urease activity, is a kind of anti-inflammatory drug that inhibition urase effect is good, can also be used as urease inhibitor use.
Technical solution of the present invention is as follows:
Step 1. with the naproxen solution and copper nitrate solution of ethyl alcohol acetonitrile mixed solution configuration 0.1mmol/mL, claims respectively
Measure 1, the 3- propane diamine liquid of 0.5mmol.
The naproxen solution of step 2. precise certain volume and the copper nitrate solution of certain volume, the room temperature in beaker
It is mixed 30 minutes, later, 1, the 3- propane diamine liquid of certain volume is slowly added dropwise into beaker, stir 3 in mixed at room temperature
Hour.
Step 3. filtering reacting liquid is to 5mL bottle.Bottleneck covers sealed membrane, and sealed membrane pricks hole with needle, is stored at room temperature slowly
Volatilization has crystal precipitation after a couple of days.
Step 4. filters vial solutions, obtains blue bulk crystals, is rinsed with mother liquor, until vacuum oven is dry.
Step 5. gained crystal carries out structured testing with single crystal X diffraction instrument, tests it with the phenol red method of urase and inhibits urase living
Property.
Detailed description of the invention
[Fig. 1] is the X- diffraction mono-crystalline structures figure that the present invention implements the complex.
Specific embodiment
By following case study on implementation, the present invention will be described in detail, but the scope of the present invention is not by any limit of these embodiments
System.
Embodiment:
The configuration of naproxen solution (0.1mmol/mL): precise naproxen 0.23g (1mmol) is dissolved in 10mL ethyl alcohol second
Nitrile mixed solution (ethyl alcohol: acetonitrile=1: 1).
The configuration of copper nitrate solution (0.1mmol/mL): precise copper nitrate [Cu (NO3)2·6H2O]0.1208g
(0.5mmol) is dissolved in 5mL ethyl alcohol acetonitrile mixed solution (ethyl alcohol: acetonitrile=3: 2).
The weighing of 1,3- propane diamine: precise 1,41.67 μ L (0.5mmol) of 3- propane diamine.
Precise naproxen solution (0.1mmol/mL) 10mL and copper nitrate solution (0.1mmol/mL) 5mL are in beaker
In, mixed at room temperature stirs 30 minutes, then is added dropwise 1,41.67 μ L of 3- propane diamine liquid (0.5mmol), and mixed at room temperature stirs 3 hours.
Filtering reacting liquid is sealed with sealed membrane, pricks hole with needle, has blue bulk crystals to be precipitated wait be stored at room temperature slow volatilization, after a couple of days,
Solution filtering, gained crystal are rinsed with mother liquor, set vacuum oven and be dried to obtain complex monocrystal.It is tied through X-ray diffraction
Structure test, crystal structure figure is as shown in Fig. 1, and crystal data is shown in Table 1, molecular formula C31H38Cu N2O7。
After tested, complex is a mononuclear structure, each complex molecule contain 2 naproxen molecules, 1 copper from
Son, 1, a 3- propane diamine molecule and a hydrone.
The complex majority crystallographic structure data of the present invention of table 1
Embodiment: naproxen copper complex inhibits urease activity test
(1) preparation of drug solution: weighing a certain amount of complex of the present invention, with 10mL dmso solution, configuration
The medical fluid of 200 μm of ol/L.The medical fluid prepared (200 μm of ol/L) doubling dilution is obtained into 200,100,50,25,12.5,6.25 μ
The medical fluid of mol/L concentration.
Positive control drug uses acetohydroxamic acid (N- hydroxyl acetamide, CAS:546-88-3), and configuration method is same as above, configuration
Concentration gradient are as follows: the medical fluid of 200,100,50,25,12.5,6.25 μm of ol/L concentration.
(2) preparation of buffer solution: the phosphate buffer 100mL:0.2mol/L sodium dihydrogen phosphate 51mL of pH6.8,
0.2mol/L disodium hydrogen phosphate 49mL, 500mmol/L urea, 0.002g/100mL are phenol red.
Phosphate buffer 100mL:0.2mol/L sodium dihydrogen phosphate 10.5mL, the 0.2mol/L disodium hydrogen phosphate of pH7.7
89.5mL, 0.002g/100mL are phenol red, 0.45 μm of membrane filtration.
(3) it is the urase solution of (40kU/L) with concentration: according to urase unit of activity number, weighs a certain amount of urase, it is molten
Solution obtains the urase solution of 40kU/L in deionized water.
(4) the buffer OD value measurement of pH 7.7: adding the 200 μ L of phosphate buffer of pH7.7 in 96 orifice plates, if 3 repetitions,
OD value is surveyed, average value is denoted as OD7.7.
(5) blank control is tested: 25 μ L urase solution (40kU/L) being added in 96 orifice plates, 25 μ L prepare above-mentioned (1) medical fluid
Solvent for use, every kind of drug concentration set 3 groups of repetitions, are put into one hour of culture in 37 DEG C of constant incubators.It is taken out after one hour,
The 200 μ L of phosphate buffer of pH6.8 is added, starts timing, and tested its OD value every 1 minute, with the extension of time, slow
Urea is decomposed by urase in fliud flushing produces ammonia, and system pH increases, and under the action of phenolic red indicator, OD value rises.Record OD value
Reach the time used in above-mentioned (4) OD7.7, is denoted as TBlank。
(6) 25 μ L urase solution (40kU/L), the 25 various concentration liquids of μ L, every kind of medicine sample test: are added in 96 orifice plates
Object concentration sets 3 repetitions, is put into one hour of culture in 37 DEG C of constant incubators.It is taken out after one hour, adds the phosphorus of pH6.8
200 μ L of acid buffer starts timing, and tested its OD value every 1 minute, and record OD value reaches the time used in OD7.7, is denoted as
TSample。
(7) data calculate: inhibiting rate=(TSample-TBlank)/TSample, IC is calculated with Origin or SPSS software50.Press down when experiment
Rate processed should be more than 50%, and the guaranteed discharge-enough ranges of effect curve crosses can not extrapolate and calculate IC50Value.
Complex of the present invention inhibits the IC of urase50Value is 1.69 μm of ol/L, i.e., when naproxen Cu complex concentration is
50% is reached to the inhibiting rate of urease activity when 1.69 μm of ol/L.The IC of positive control drug acetohydroxamic acid50Value is 6.26 μm of ol/
L.Thus illustrate, it is a kind of tool that the inhibition urase effect of complex of the present invention is got well than positive control drug acetohydroxamic acid
There is the anti-inflammatory drug for inhibiting urease activity, can also be used as urease inhibitor exploitation and use.
Claims (3)
1. it is a kind of with inhibit urease activity naproxen copper complex, it is characterised in that: the complex be with naproxen and 1,
3- propane diamine is ligand, using copper ion as the mononuclear structure of center ion.
2. a kind of preparation method with the naproxen copper complex for inhibiting urease activity described in claim 1, feature exist
In: naproxen, copper nitrate and 1,3- propane diamine is according to molar ratio (1.9-2.1): (0.9-1.1): (0.9-1.1) is dissolved in ethyl alcohol
And acetonitrile mixed solution, it is stored at room temperature slowly volatilization and is prepared.
3. a kind of purposes with the naproxen copper complex for inhibiting urease activity described in claim 1, it is characterised in that: tool
There is preferable inhibition urease activity, can be used as urease inhibitor prepares raw material.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111072725A (en) * | 2019-12-06 | 2020-04-28 | 聊城大学 | Compound with naproxen tetravalent platinum structure, preparation method and application thereof in preparation of antitumor drugs |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007109845A1 (en) * | 2006-03-28 | 2007-10-04 | Medical Therapies Limited | Prophylaxis or treatment of diabetes |
| WO2008074087A1 (en) * | 2006-12-21 | 2008-06-26 | The University Of Western Australia | Method for coating nanoparticles |
-
2018
- 2018-01-24 CN CN201810086423.8A patent/CN110066288A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007109845A1 (en) * | 2006-03-28 | 2007-10-04 | Medical Therapies Limited | Prophylaxis or treatment of diabetes |
| WO2008074087A1 (en) * | 2006-12-21 | 2008-06-26 | The University Of Western Australia | Method for coating nanoparticles |
Non-Patent Citations (1)
| Title |
|---|
| 周林霞: "铜(Ⅱ) -萘普生-1，10-邻菲罗啉配合物的合成、表征及磁性质研究", 《化学试剂》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111072725A (en) * | 2019-12-06 | 2020-04-28 | 聊城大学 | Compound with naproxen tetravalent platinum structure, preparation method and application thereof in preparation of antitumor drugs |
| CN111072725B (en) * | 2019-12-06 | 2023-04-21 | 聊城大学 | Compound with naproxen tetravalent platinum structure, preparation method and application thereof in preparation of antitumor drugs |
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