CN108690090A - A kind of preparation method of the Schiff base complex of ruthenium and its antitumor application - Google Patents
A kind of preparation method of the Schiff base complex of ruthenium and its antitumor application Download PDFInfo
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- CN108690090A CN108690090A CN201810706071.1A CN201810706071A CN108690090A CN 108690090 A CN108690090 A CN 108690090A CN 201810706071 A CN201810706071 A CN 201810706071A CN 108690090 A CN108690090 A CN 108690090A
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- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 229910052707 ruthenium Inorganic materials 0.000 title claims abstract description 47
- 239000002262 Schiff base Substances 0.000 title claims abstract description 39
- 150000004753 Schiff bases Chemical class 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 230000000259 anti-tumor effect Effects 0.000 title claims abstract description 14
- 239000012046 mixed solvent Substances 0.000 claims abstract description 43
- 239000003446 ligand Substances 0.000 claims abstract description 23
- 150000001875 compounds Chemical class 0.000 claims abstract description 16
- 239000013078 crystal Substances 0.000 claims abstract description 13
- 150000003303 ruthenium Chemical class 0.000 claims abstract description 11
- 150000002460 imidazoles Chemical class 0.000 claims abstract description 7
- 238000001816 cooling Methods 0.000 claims abstract description 5
- 238000010438 heat treatment Methods 0.000 claims abstract description 5
- 238000001914 filtration Methods 0.000 claims abstract description 3
- 238000013019 agitation Methods 0.000 claims abstract 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 10
- 238000010792 warming Methods 0.000 claims description 10
- -1 5- methoxysalicyl aldehydes Chemical class 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- ZMXYNJXDULEQCK-UHFFFAOYSA-N 2-amino-p-cresol Chemical class CC1=CC=C(O)C(N)=C1 ZMXYNJXDULEQCK-UHFFFAOYSA-N 0.000 claims description 7
- 238000005575 aldol reaction Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 claims description 6
- 235000019441 ethanol Nutrition 0.000 claims description 5
- 238000010583 slow cooling Methods 0.000 claims description 5
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 208000019065 cervical carcinoma Diseases 0.000 claims description 4
- 201000007270 liver cancer Diseases 0.000 claims description 4
- 208000014018 liver neoplasm Diseases 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- ONAOBFWXMNPKEQ-UHFFFAOYSA-N 2-methylperoxybenzaldehyde Chemical compound COOC1=CC=CC=C1C=O ONAOBFWXMNPKEQ-UHFFFAOYSA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- JJVNINGBHGBWJH-UHFFFAOYSA-N methoxysalicylaldehyde Natural products COC1=CC=CC(C=O)=C1O JJVNINGBHGBWJH-UHFFFAOYSA-N 0.000 claims 1
- 238000011160 research Methods 0.000 abstract description 5
- 239000002246 antineoplastic agent Substances 0.000 abstract description 4
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 4
- 238000012805 post-processing Methods 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 14
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 10
- 229910052697 platinum Inorganic materials 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 8
- 201000011510 cancer Diseases 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical class CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 238000002447 crystallographic data Methods 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 201000005296 lung carcinoma Diseases 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 206010033109 Ototoxicity Diseases 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000000686 essence Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 231100000262 ototoxicity Toxicity 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 150000003057 platinum Chemical class 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000010408 sweeping Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
- C07F15/0053—Ruthenium compounds without a metal-carbon linkage
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
Abstract
The invention discloses a kind of preparation method of Schiff base complex of ruthenium and its antitumor applications.The present invention is by under constant agitation state, being dissolved in the mixed solvent by ruthenium salt, obtaining solution 1;Then Schiff ligand compound is dissolved in the mixed solvent, and imidazoles is added and obtains solution 2, solution 1 is added in solution 2,0.5~1.0h of constant agitation obtains solution 3 after filtering;Solution 3 is placed in autoclave again, after program control heating and cooling, obtains the Schiff base complex of red-brown crystals ruthenium.The Schiff base complex of ruthenium of the present invention has that stability of crystal form is good, preparation method and post processing mode are also relatively simple, in terms of can be applicable to antitumor activity, has the advantages such as antitumor activity is apparent, can provide important evidence for the research of follow-up antitumor drug.
Description
Technical field
The invention belongs to the preparation method of anticancer drug technical field more particularly to a kind of Schiff base complex of ruthenium and
Its antitumor application.
Background technology
Cancer is the disease that the death rate second is high in the world, has seriously affected people's health.For treating cancer, people
Have developed a variety for the treatment of means and technology, mainly there is operative treatment, chemotherapy and radiotherapy etc., but be to a greater extent with
Based on chemotherapy.Chemotherapy is that a kind of active effective method of cancer cell is killed by chemicals.1969
Year, people reported cis-platinum to tumor disease with good inhibiting effect and clinical therapeutic efficacy for the first time, but platinum complex exists
The shortcomings such as toxic side effect is big, water solubility is small, to clinically renal toxicity, ototoxicity, neurotoxicity etc. be caused many
Side effect.Therefore, scientist has carried out numerous studies to other metal complexs except platinum, find ruthenium be expected to become after platinum it
One of the metal of high activity, hypotoxicity afterwards can play a significant role and generate excellent treatment in cancer treatment procedure
Effect.A large amount of research report confirms:Ruthenium anticancer complex has hypotoxicity, easily absorbs, the features such as Small side effects, is easy swollen
Tumor tissue position be enriched with and absorb, can rapid drainage go out not influencing in vitro people eubolism recycle.And Schiff class is matched
Some the functional functional groups contained in body.It is with some required physicochemical properties of all kinds of biological phenomenas and preferably anti-thin
Bacterium, antiviral and antitumor activity.The ligand of Schiff class and ruthenium metal are coordinated and to form complex and can further increase it
The property of antitumor activity.In recent years, the research in relation to Schiff base complex antitumor activity has certain report.But about gold
Belong to the research that the complex that ruthenium is formed with Schiff class compound acts on tumour cell to be rarely reported.
Invention content
The primary purpose of the present invention is that provide a kind of Schiff base complex of ruthenium, the Schiff base complex of the ruthenium with
Cis-platinum is compared, and has relatively low toxicity, highly selective, is easily absorbed in vivo and is drained and overcomes the thin of platinum medicine quickly
The features such as born of the same parents' drug resistance.
It is still another object of the present invention to provide the preparation methods of the Schiff base complex of above-mentioned ruthenium.
It is still another object of the present invention to provide application of the Schiff base complex of above-mentioned ruthenium in terms of antitumor activity.
The invention is realized in this way a kind of Schiff base complex of ruthenium, the molecular formula of the complex are:C24H25Cl
Ru N7O3, shown in chemical structural formula such as following formula (I):
The present invention further discloses the preparation method of the Schiff base complex of above-mentioned ruthenium, this method includes following step
Suddenly:
(1) under stirring, ruthenium salt is dissolved in the mixed solvent, obtains solution 1;Wherein, the ruthenium salt (20.74mg,
0.1mmol) it is dissolved in the in the mixed solvent of (3~5) mL;
(2) Schiff ligand compound is dissolved in the in the mixed solvent of 4ml and imidazoles (20.42,0.3mmol) is added
0.5-1h is stirred, solution 2 is obtained.The solution 1 that step (1) obtains is added in solution 2, stir about 0.5-1h, after filtering
To solution 3;Wherein, the mass volume ratio of Schiff ligand compound and mixed solvent is 25.72mg:(3-5)mL;The ruthenium
The molar ratio of salt and Schiff ligand compound is 1:1.
In step (1), step (2), the mixed solvent is by two or more in methanol, acetonitrile, ethyl alcohol and isopropanol
Component is constituted;
(3) solution 3 that step (2) obtains is continuously stirred at room temperature 0.5~1.0h and is placed on autoclave, program
After control heating and cooling, the Schiff base complex of the ruthenium of red-brown crystals is obtained.
Preferably, in step (1), the ruthenium salt is ruthenium trichloride, the mass volume ratio of the ruthenium salt and mixed solvent
It is 20.74:4mL.
Preferably, in step (2), the mass volume ratio of the Schiff ligand compound and mixed solvent is ranging from
25.72:5mL;
The molar ratio of the ruthenium salt and Schiff ligand compound is 1:1;
In step (2), the preparation of the Schiff ligand compound includes the following steps:By 5- methoxysalicyl aldehydes
It is dissolved in mixed solvent generation aldol reaction with 2- amino -4- methylphenols and obtains Schiff ligand compound;Wherein, institute
State the molal volume ratio 0.1mmol of 5- methoxysalicyl aldehydes, 2- amino -4- methylphenols, mixed solvent:0.1mmol:(1~5)
mL。
Preferably, in step (2), the 5- methoxysalicyl aldehydes, 2- amino -4- methylphenols, mixed solvent rub
Your volume ratio is 0.1mmol:0.1mmol:5mL.
Preferably, in step (1) or step (2), the mixed solvent is by being (1~5) by volume:1 methanol and
Acetonitrile is constituted, alternatively, the mixed solvent is by being (1~5) by volume:2 acetonitrile and isopropanol is constituted, alternatively, described mixed
Bonding solvent is by being 1 by volume:The ethyl alcohol and isopropanol of (1~5) are constituted.
Preferably, the mixed solvent is by being 1 by volume:2 methanol and acetonitrile is constituted.
Preferably, in step (3), described program control heating and cooling are specially:Temperature rise is set to be kept to 80 DEG C
1h continues to be warming up to 120 DEG C of 6~8h of holding, is gradually warming up to 180 DEG C of holding 12-16h, then slow cooling to 120 DEG C of holdings
4-6h cools to 80 DEG C of holding 1h, is finally down to room temperature.
The present invention further discloses application of the Schiff base complex of above-mentioned ruthenium in terms of antitumor activity.
Preferably, the tumour includes Human Breast Cancer, cervical carcinoma, liver cancer, lung cancer.
The present invention overcomes the deficiencies of the prior art and provide a kind of preparation method of the Schiff base complex of ruthenium and its anti-
Application in terms of tumor promotion.The present invention is made using mixed solvent dissolving 5- methoxysalicyl aldehydes and 2- amino -4- methylphenols
Its occur aldol reaction, the in the mixed solvent being dissolved in by ruthenium trichloride, then with a certain amount of Schiff ligand and
Imidazoles enters in autoclave together, and the Schiff base complex of ruthenium is obtained after being controlled by temperature programming, passes through mtt assay pair
The Schiff base complex of ruthenium carries out antitumor cytolytic activity, and experiment shows that the complex is thin to human breast cancer cell, cervical carcinoma
Born of the same parents, liver cancer cells, lung carcinoma cell have obvious inhibiting effect, and inhibiting rate significant effect, this is for future studies platinum class Schiff
The antitumor drug of complex has important meaning.
Compared with the prior art the shortcomings that and deficiency, the invention has the advantages that:The Schiff of ruthenium of the present invention
The advantages such as complex has good stability of crystal form, preparation method and post processing mode also relatively simple, and antitumor activity is apparent,
Important evidence is provided for the research of follow-up antitumor drug.
Description of the drawings
Fig. 1 is the crystal structure figure of the Schiff base complex of ruthenium of the present invention.
Specific implementation mode
In order to make the purpose , technical scheme and advantage of the present invention be clearer, with reference to the accompanying drawings and embodiments, right
The present invention is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, and
It is not used in the restriction present invention.
Embodiment 1
It is by volume by acetonitrile and isopropanol (1~5):Mixed solvent 1 is obtained after 2 mixing;
It is 1 by volume by ethyl alcohol and isopropanol:(1~5) mixed solvent 2 is obtained after mixing.
It is 1 by volume by methanol and acetonitrile:Mixed solvent 3 is obtained after 2 mixing.
Embodiment 2
2- amino -4- the methylphenols of the 5- methoxysalicyl aldehydes of 0.1mmol and 0.1mmol are dissolved in 3mL mixed solvents 1
Aldol reaction occurs and obtains Schiff ligand compound 1.
Embodiment 3
2- amino -4- the methylphenols of the 5- methoxysalicyl aldehydes of 0.1mmol and 0.1mmol are dissolved in 4mL mixed solvents 2
Aldol reaction occurs and obtains Schiff ligand compound 2.
Embodiment 4
2- amino -4- the methylphenols of the 5- methoxysalicyl aldehydes of 0.1mmol and 0.1mmol are dissolved in 5mL mixed solvents 3
Aldol reaction occurs and obtains Schiff ligand compound 3.
Embodiment 5
(1) under stirring, 20.74mg ruthenium trichlorides are dissolved in 4mL mixed solvents 1, obtain solution 1;
(2) the Schiff ligand compound 1 of 25.72mg is dissolved in 3mL mixed solvents 1, and imidazoles is added
(20.42mg, 0.3mmol) obtains solution 2, the solution 1 that step (1) obtains is added in solution 2, stir about 0.5-1h, mistake
Solution 3 is obtained after filter;
(3) solution 3 that step (2) obtains is continuously stirred at room temperature 0.5h and is placed on autoclave, program control
Make temperature rise to 80 DEG C of holding 1h, continues to be warming up to 120 DEG C of 6~8h of holding, be gradually warming up to 180 DEG C of holding 12-16h, so
Slow cooling cools to 80 DEG C of holding 1h, is finally down to room temperature to 120 DEG C of holding 4-6h afterwards.Obtain the ruthenium of red-brown crystals
Schiff base complex 1.
Embodiment 6
(1) under stirring, 20.74mg ruthenium trichlorides are dissolved in 5mL mixed solvents 2, obtain solution 1;
(2) the Schiff ligand compound 1 of 25.72mg is dissolved in 6mL mixed solvents 1, and imidazoles is added
(20.42mg, 0.3mmol) obtains solution 2, the solution 1 that step (1) obtains is added in solution 2, stir about 0.5-1h, mistake
Solution 3 is obtained after filter;
(3) solution 3 that step (2) obtains is continuously stirred at room temperature 1.0h and is placed on autoclave, program control
Make temperature rise to 80 DEG C of holding 1h, continues to be warming up to 120 DEG C of 6~8h of holding, be gradually warming up to 180 DEG C of holding 12-16h, so
Slow cooling cools to 80 DEG C of holding 1h, is finally down to room temperature to 120 DEG C of holding 4-6h afterwards.Obtain the ruthenium of red-brown crystals
Schiff base complex 2.
Embodiment 7
(1) under stirring, 20.74mg ruthenium trichlorides are dissolved in 4mL mixed solvents 3, obtain solution 1;
(2) the Schiff ligand compound 3 of 25.72mg is dissolved in 5mL mixed solvents 3, and imidazoles is added
(20.42mg, 0.3mmol) obtains solution 2, the solution 1 that step (1) obtains is added in solution 2, stir about 0.5-1h, mistake
Solution 3 is obtained after filter;
(3) solution 3 that step (2) obtains is continuously stirred at room temperature 0.8h and is placed on autoclave, program control
Make temperature rise to 80 DEG C of holding 1h, continues to be warming up to 120 DEG C of 6~8h of holding, be gradually warming up to 180 DEG C of holding 12-16h, so
Slow cooling cools to 80 DEG C of holding 1h, is finally down to room temperature to 120 DEG C of holding 4-6h afterwards.Obtain the ruthenium of red-brown crystals
Schiff base complex 3.
Effect example 1
The Schiff base complex 3 of the ruthenium of the red-brown crystals obtained in embodiment 7 is filtered, it is molten with mixing on a small quantity
Agent 3 washs crystal 3 times, is then dried in vacuo, and it is 36% to calculate yield.
Elemental analysis is carried out to the Schiff base complex 3 of obtained ruthenium, result is:C24H25Cl Ru N7O3It (calculates
Value) C, 48.36;H,4.23;N,16.45;(test value) C, 48.33;H, 4.20;N, 16.46.
3 mono-crystalline structures of Schiff base complex of ruthenium are to visit diffractometer using the faces Bruker SMART 1000CCD to be surveyed
Examination, use wavelength forMoK alpha rays, ω surface sweeping modes.Using SAINT programs to collected point diffraction
Data convert is carried out, Data correction is carried out with SADABS programs.Based on the method for full-shape least square, SHELXTL 5.1 is utilized
Program bag finds out the coordinate of whole non-hydrogen atoms with direct method on difference Fourier figure, then all by all non-hydrogen atoms
Using anisotropy refine.
The crystallographic parameter of the Schiff base complex 3 of ruthenium is as shown in the following table 1, table 2:
3 crystallographic data of Schiff complexs of 1 ruthenium of table
R1=∑ ||Fo|-|Fc||/∑|Fo|, wR2=[∑w(Fo 2-Fc 2)2/∑w(Fo 2)2]1/2.
The part bond distance of 2 complex of tableWith bond angle (o) data
Effect example 2
With the Schiff base complex 3 of the ruthenium obtained in embodiment 7 come analyze its to tumour cell MCF-7, HeLa,
The inhibiting effect of A549, HepG2.
In this effect example, the in vitro toxicity that complex is had studied using mtt assay is tested.Experimental cell is placed in 37
DEG C, 5.0%RU2Logarithmic phase is grown in incubator, 0.25% collected by trypsinisation cell adjusts concentration of cell suspension, makes thin
Born of the same parents' density is about 1 × 104A/mL is inoculated in 96 orifice plates per hole 100mL, and cell density is about 3~5 × 103A/hole, is placed in
37 DEG C, 5%RU2Incubator in cultivate for 24 hours.Liquid to be changed, the drug of various concentration gradient is added, each concentration does 3 Duplicate Samples,
Be arranged blank zeroing group (culture medium, MTT, DMSO), blank group (culture medium, cell, same concentrations drug dissolving medium,
MTT, DMSO), positive controls (culture medium, cell, the cis-platinum of various concentration, MTT, DMSO).It is placed in 37 DEG C, 5%RU2Training
It supports and continues to cultivate 48h in case.Suck supernatant, per hole be added 90 μ l fresh mediums, add 10 μ l MTT solution (5mg/mL,
That is 0.5%MTT), continue to cultivate 4h.Culture is terminated, culture solution in hole is discarded, 150 μ l DMSO are added per hole, are placed on shaking table
Low-speed oscillation 30min, makes crystal fully dissolve.Enzyme-linked immunosorbent assay instrument detects the absorbance value OD in each hole of 490nm wavelength
The inhibiting rate and half-inhibition concentration (IC of relevant cell Proliferation50) calculated with following formula:Growth inhibition ratio=(OD
Control-OD experiment)/(OD control-OD blank), all OD values subtract blank zeroing group OD values.The Schiff base complex of ruthenium
To MCF-7 (human breast cancer cell), HeLa (human cervical carcinoma cell), A549 (lung carcinoma cell), HepG2 (liver cancer cells) proliferation suppressions
The IC of making50Value is as shown in table 3 below.
Table 3
As can be known from the table data, the complex 3 of the Schiff ruthenium in example 7 shows fine suppression to above-mentioned tumour cell
It makes and uses.16.4 ± 2.4IC especially can be reached to MCF-7 inhibiting effect50μM inhibiting rate is 1.2 times of cis-platinum, the inhibition of HeLa
Effect can reach 16.2 ± 2.4IC50μM inhibiting rate is 1.4 times of cis-platinum.Reason may be the distinctive antibacterial of Schiff, inhibition
Tumor promotion simultaneously combines the complex that the metal salt of ruthenium is formed can be more advantageous on inhibition tumour cell on this basis.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
All any modification, equivalent and improvement etc., should all be included in the protection scope of the present invention made by within refreshing and principle.
Claims (10)
1. a kind of Schiff base complex of ruthenium, which is characterized in that the molecular formula of the complex is:C24H25Cl Ru N7O3, change
It learns shown in structural formula such as following formula (I):
2. the preparation method of the Schiff base complex of ruthenium described in claim 1, which is characterized in that this method includes following step
Suddenly:
(1) under constant agitation state, ruthenium salt is dissolved in the mixed solvent, obtains solution 1;Wherein, the ruthenium salt (20.74mg,
0.1mmol) it is dissolved in the in the mixed solvent of (3~5) mL.
(2) Schiff ligand compound is dissolved in the in the mixed solvent of 10ml and imidazoles (20.42mg, 0.3mmol) is added,
0.5-1h is stirred, solution 2 is obtained.The solution 1 that step (1) obtains is added in solution 2, stir about 0.5-1h, after filtering
To solution 3;Wherein, the mass volume ratio of Schiff ligand compound and mixed solvent is 25.72mg:(3-5)mL;The ruthenium
The molar ratio of salt and Schiff ligand compound is 1:1;
In step (1), step (2), the mixed solvent is by the two or more components in methanol, acetonitrile, ethyl alcohol and isopropanol
It constitutes;
(3) by solution 3 that step (2) obtains, the filtered solution of 0.5~1.0h of constant agitation is placed in reaction under high pressure at room temperature
Kettle obtains the Schiff base complex of red-brown crystals ruthenium after program control heating and cooling.
3. the preparation method of the Schiff base complex of ruthenium as claimed in claim 2, which is characterized in that in step (1), institute
Ruthenium salt is stated as ruthenium trichloride, the mass volume ratio of the ruthenium salt and mixed solvent is 20.74mg:4mL.
4. the preparation method of the Schiff base complex of ruthenium as claimed in claim 2, which is characterized in that in step (2), institute
State the mass volume ratio ranging from 25.72mg of Schiff ligand compound and mixed solvent:5mL;
The molar ratio of the ruthenium salt and Schiff ligand compound is 1:1;
In step (2), the preparation of the Schiff ligand compound includes the following steps:By 5- methoxysalicyl aldehydes and 2-
Amino -4- methylphenols are dissolved in mixed solvent generation aldol reaction and obtain Schiff ligand compound;Wherein, the 5-
The molal volume ratio 0.1mmol of methoxysalicyl aldehyde, 2- amino -4- methylphenols, mixed solvent:0.1mmol:(3~5) mL.
5. the preparation method of the Schiff base complex of ruthenium as claimed in claim 4, which is characterized in that in step (2), institute
State 5- methoxysalicyl aldehydes, 2- amino -4- methylphenols, mixed solvent molal volume ratio be 0.1mmol:0.1mmol:5mL.
6. the preparation method of the Schiff base complex of ruthenium as claimed in claim 2, which is characterized in that in step (1) or step
Suddenly in (2), the mixed solvent is by being (1~5) by volume:1 methanol and acetonitrile are constituted, alternatively, the mixed solvent by
It is by volume (1~5):2 acetonitrile and isopropanol is constituted, alternatively, the mixed solvent is by being 1 by volume:(1~5)
Ethyl alcohol and isopropanol are constituted.
7. the preparation method of the Schiff base complex of ruthenium as claimed in claim 6, which is characterized in that the mixed solvent by
It is 1 by volume:2 methanol and acetonitrile is constituted.
8. the preparation method of the Schiff base complex of ruthenium as claimed in claim 2, which is characterized in that in step (3), institute
It states program control heating and cooling is specially:Temperature rise continues to be warming up to 120 DEG C of 6~8h of holding, gradually to 80 DEG C of holding 1h
180 DEG C of holding 12-16h are warming up to, then slow cooling to 120 DEG C of holding 4-6h, cools to 80 DEG C of holding 1h, be finally down to room
Temperature.Obtain the Schiff base complex 1 of the ruthenium of red-brown crystals.
9. application of the Schiff base complex of ruthenium described in claim 1 in terms of antitumor activity.
10. application as claimed in claim 9, which is characterized in that the tumour includes Human Breast Cancer, cervical carcinoma, liver cancer, lung
Cancer.
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