CN104277076B - Compound for enhancing anti-infection capacity of plants, and preparation method and application thereof - Google Patents
Compound for enhancing anti-infection capacity of plants, and preparation method and application thereof Download PDFInfo
- Publication number
- CN104277076B CN104277076B CN201410513757.0A CN201410513757A CN104277076B CN 104277076 B CN104277076 B CN 104277076B CN 201410513757 A CN201410513757 A CN 201410513757A CN 104277076 B CN104277076 B CN 104277076B
- Authority
- CN
- China
- Prior art keywords
- compound
- weight portions
- atcc
- preparation
- phenyl
- 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.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 36
- 230000002924 anti-infective effect Effects 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title abstract description 11
- 230000002708 enhancing effect Effects 0.000 title abstract 3
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 5
- 239000003814 drug Substances 0.000 claims abstract description 4
- 238000002513 implantation Methods 0.000 claims description 25
- 230000003834 intracellular effect Effects 0.000 claims 1
- YAYGSLOSTXKUBW-UHFFFAOYSA-N ruthenium(2+) Chemical compound [Ru+2] YAYGSLOSTXKUBW-UHFFFAOYSA-N 0.000 abstract description 9
- 239000000126 substance Substances 0.000 abstract description 6
- 208000015181 infectious disease Diseases 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 4
- 210000000963 osteoblast Anatomy 0.000 abstract description 4
- 244000063299 Bacillus subtilis Species 0.000 abstract description 3
- 235000014469 Bacillus subtilis Nutrition 0.000 abstract description 3
- 241000222122 Candida albicans Species 0.000 abstract description 3
- 241000191967 Staphylococcus aureus Species 0.000 abstract description 3
- 229940095731 candida albicans Drugs 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 2
- 241000588724 Escherichia coli Species 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 231100000956 nontoxicity Toxicity 0.000 abstract 1
- 230000001737 promoting effect Effects 0.000 abstract 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 54
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000000047 product Substances 0.000 description 13
- YKFLAYDHMOASIY-UHFFFAOYSA-N γ-terpinene Chemical compound CC(C)C1=CCC(C)=CC1 YKFLAYDHMOASIY-UHFFFAOYSA-N 0.000 description 12
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 229960000935 dehydrated alcohol Drugs 0.000 description 10
- 238000001556 precipitation Methods 0.000 description 10
- 150000003583 thiosemicarbazides Chemical class 0.000 description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- 238000003682 fluorination reaction Methods 0.000 description 8
- ODEKYHUPQWAKDE-UHFFFAOYSA-N CC1=C(C=CC=C1)C(C)C.C1(=CC=CC=C1)NC(NN)=S Chemical compound CC1=C(C=CC=C1)C(C)C.C1(=CC=CC=C1)NC(NN)=S ODEKYHUPQWAKDE-UHFFFAOYSA-N 0.000 description 7
- 239000012327 Ruthenium complex Substances 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 7
- 239000001963 growth medium Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 229910052707 ruthenium Inorganic materials 0.000 description 6
- BIXNGBXQRRXPLM-UHFFFAOYSA-K ruthenium(3+);trichloride;hydrate Chemical compound O.Cl[Ru](Cl)Cl BIXNGBXQRRXPLM-UHFFFAOYSA-K 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 239000012467 final product Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- 0 CC(N(*C(Nc1ccccc1)=S1)[Ru]1(C)Cl)F Chemical compound CC(N(*C(Nc1ccccc1)=S1)[Ru]1(C)Cl)F 0.000 description 2
- 125000006519 CCH3 Chemical group 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- -1 aryl ruthenium Chemical compound 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N deuterated chloroform Substances [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 108010011619 6-Phytase Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010065687 Bone loss Diseases 0.000 description 1
- AAIXZDBTEWDLSG-UHFFFAOYSA-N CC(C)C1=CCC(C)C=C1 Chemical compound CC(C)C1=CCC(C)C=C1 AAIXZDBTEWDLSG-UHFFFAOYSA-N 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000002158 anti-implantation Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 210000004513 dentition Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 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
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000004072 osteoblast differentiation Effects 0.000 description 1
- 230000001582 osteoblastic effect Effects 0.000 description 1
- 210000004409 osteocyte Anatomy 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229940085127 phytase Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000036346 tooth eruption Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 238000012549 training Methods 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a compound for enhancing anti-infection capacity of plants disclosed as structural formula (I), and a preparation method and application thereof. The chemical name is monochlorinated-chloro-p-fluoridated-phenyl-2-N＜4＞-phenylthiosemicarbazidomonomethylisopropylbenzo ruthenium (II). The compound has strong bactericidal activity for Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 25922), Candida albicans (ATCC 10231) and Bacillus subtilis black variant (ATCC 9372), has the advantages of excellent mold resistance and no toxicity, has the function of promoting growth of osteoblasts, is used for preparing drugs for enhancing plant performance and preventing plant related infections, and has obvious application potential. The preparation method is simple, and has the advantages of accessible raw materials and low cost.
Description
Technical field
The present invention relates to field of compound preparation, and in particular to a kind of aryl ruthenium for improving implantation body's anti-infection ability
Coordination compound and its production and use.
Background technology
The planting material such as tooth implant and bone planting body has become the important restorative procedure of defect of dentition and bone loss, so
And the infection rate of such operation is very high, may result in a large amount of antibiotic therapies, remove implantation body's even serious consequence such as death.
Implantation body's infections relating main cause occurred frequently has at 2 points：Bacterial plaque is in implant surface aggregation and the opposing of Osseointegrated implants interface
Inferior capabilities.In order to avoid implantation body's infections relating, graft should have both sides premium properties：Excellent anti-microbial property and
Promote Oesteoblast growth function.Therefore, finding the compound with both the above performance is used to improving implantation body's performance and pre-
Anti- implantation body's infections relating is necessary.
The content of the invention
It is an object of the invention to according to the research of existing aryl ruthenium complex, there is provided a kind of aryl ruthenium complex and its system
Preparation Method and purposes.
The present invention provide technical scheme be：
A kind of compound for improving implantation body's anti-infection ability, its structural formula is formula (I)：
Wherein in one embodiment, compound of the present invention is, for example, aryl ruthenium complex, and its chemical name is one
One chlorine of chlorination, a pair of fluorination benzene -2- contracting N4- phenyl thiosemicarbazide monomethyl cumene closes ruthenium (II)；
Its structural formula is：
Its physicochemical property is：Kermesinus crystal, soluble in water and organic solvent, its hydrogen nuclear magnetic resonance modal data is1H NMR
(CDCl3Solvent)：δ：8.903 (1H, s, CH=N), 8.429-8.382 (2H, m, phenyl-H), 7.505-7.424 (7H, m,
Phenyl-H), 5.765 (1H, d, J=6.0Hz, p-cym phenyl-H), 5.202 (1H, d, J=5.9Hz, p-cym
Phenyl-H), 5.092 (1H, d, J=6.0Hz, p-cym phenyl-H), 5.046 (1H, d, J=6.0Hz, p-cym
Phenyl-H), 2.713-2.621 (1H, m, p-cym CH (CH3)2), 2.117 (3H, s, p-cym CCH3), 1.224 (3H, d, J
=6.9Hz, p-cym CH (CH3)2), 1.165 (3H, d, J=6.9Hz, p-cym CH (CH3)2)ppm.。
It is a further object to provide the preparation side for improving the compound of implantation body's anti-infection ability
Method, the compound for improving implantation body's anti-infection ability is prepared by the following method：
Step one, by the γ-terpinene of the hydrate ruthenium trichloride of 65-70 weight portions and 470-480 weight portions 1450- is dissolved in
The dehydrated alcohol of 1500 weight portions, is heated to reflux stirring 6 hours, stands precipitation and obtains the compound with formula (III), i.e. dichloro
Change two chloro- two-cymols and close two rutheniums (II)；
Step 2, weighs the N of 27-35 weight portions4The 4-Fluorobenzaldehyde of-phenyl thiosemicarbazide and 22-26 weight portions is common
The dehydrated alcohol of 870-910 weight portions is dissolved in, 70 DEG C, after 4 hours are heated to, precipitation is stood and is obtained the chemical combination with formula (IV)
Thing, i.e., 4-Fluorobenzaldehyde contracting benzene is for thiosemicarbazides；
Step 3, by the 4-Fluorobenzaldehyde contracting benzene of 4.5-5.5 weight portions for thiosemicarbazides and 4-6 weight portions dichloride two
Chloro- two-cymol closes the dichloromethane that two rutheniums (II) are dissolved in 1230-1250 weight portions, and room temperature 22-25 DEG C stirring 3 is little
When, dark red solid is separated out, obtain final product.
Preferably, the described compound for improving implantation body's anti-infection ability, is hydrated described in the step one
Ruthenium trichloride is the hydrate ruthenium trichloride that ruthenium weight content is 37%；The purity of the γ-terpinene is 95%.
Preferably, the described compound for improving implantation body's anti-infection ability, is prepared by the following method：
Step one, by the γ-terpinene of the hydrate ruthenium trichloride of 69 weight portions and 478 weight portions 1480 weight portions are dissolved in
Dehydrated alcohol, is heated to reflux stirring 6 hours, stands precipitation and obtains the compound with formula (III), i.e. dichloride-two-first
Base cumene closes two rutheniums (II)；
Step 2, weighs the N of 31 weight portions4The 4-Fluorobenzaldehyde of-phenyl thiosemicarbazide and 23 weight portions is dissolved in 888 jointly
The dehydrated alcohol of weight portion, is heated to 70 DEG C, after 4 hours, stands precipitation and obtains the compound with formula (IV), i.e., to fluorobenzene first
Al benzene is for thiosemicarbazides；
Step 3, by the 4-Fluorobenzaldehyde contracting benzene of 5.1 weight portions for thiosemicarbazides and 6 weight portions dichloride-two-
Cymol closes the dichloromethane that two rutheniums (II) are dissolved in 1244 weight portions, and room temperature 22-25 DEG C is stirred 3 hours, is separated out dark red
Color solid, obtains final product.
It is a further object to provide a kind of use for improving the compound of implantation body's anti-infection ability
On the way, it is used to prepare the medicine for improving implantation body's anti-infection ability.
Compared with the prior art, the invention has the advantages that：
First, increased phenylamino and to fluorine in the compound for improving implantation body's anti-infection ability of the present invention
Phenyl, phenyl ring forms conjugation with the carbon-to-nitrogen double bon being connected, and molecule is more stable, and so as to improve its armaticity, and its activity is more
It is high；
Secondly, the compound for improving implantation body's anti-infection ability of the present invention is to staphylococcus aureuses (ATCC
6538), colon bacillus (ATCC 25922), candida albicans (ATCC 10231), Bacillus subtilis endophyticus
(ATCC 9372) all has very strong bactericidal properties, with excellent anti-microbial property, and osteoblast is shown to promote growth
Effect, it is nontoxic, with apparent application potential.
Finally, the preparation method for improving the compound of implantation body's anti-infection ability of the present invention is simple, and raw material is easy
, the advantage with low cost.
Description of the drawings
Fig. 1 is that the nuclear-magnetism described in one of embodiment of the invention for improving the compound of implantation body's anti-infection ability is total to
Shake spectrogram.
Fig. 2 is the absorbance of the compound for being used to improve implantation body's anti-infection ability described in one of embodiment of the invention
Figure.
Fig. 3 is the alkaline phosphorus of the compound for being used to improve implantation body's anti-infection ability described in one of embodiment of the invention
Phytase activity figure.
Specific embodiment
With reference to embodiment, the present invention is described in further detail, to make those skilled in the art with reference to description
Word can be implemented according to this.
Embodiment 1：
Compound for improving implantation body's anti-infection ability of the present invention is aryl ruthenium complex, and its chemical name is
One chlorine of monochlor(in)ate, a pair of fluorination benzene -2- contracting N4- phenyl thiosemicarbazide monomethyl cumene closes ruthenium (II)；
Its structural formula is：
Its physicochemical property is：Kermesinus crystal, soluble in water and organic solvent.
One chlorine of monochlor(in)ate of the present invention, a pair of fluorination benzene -2- contracting N4- phenyl thiosemicarbazide monomethyl cumene closes ruthenium
(II) preparation method, it is comprised the following steps that：
Step one, by the hydrate ruthenium trichloride of the ruthenium weight content 37% of 65 weight portions and the purity 95% of 470 weight portions
γ-terpinene be dissolved in the dehydrated alcohol of 1450 weight portions, be heated to reflux stirring 6 hours, stand precipitation and obtain with formula (III)
Compound, i.e. dichloride-two-cymol closes two rutheniums (II)；
Step 2, weighs the N of 27 weight portions4The 4-Fluorobenzaldehyde of-phenyl thiosemicarbazide and 22 weight portions is dissolved in 870 jointly
The dehydrated alcohol of weight portion, is heated to 70 DEG C, after 4 hours, stands precipitation and obtains the compound with formula (IV), i.e., to fluorobenzene first
Al benzene is for thiosemicarbazides；
Step 3, by the 4-Fluorobenzaldehyde contracting benzene of 4.5 weight portions for thiosemicarbazides and 4 weight portions dichloride-two-
Cymol closes the dichloromethane that two rutheniums (II) are dissolved in 1230 weight portions, and room temperature 22-25 DEG C is stirred 3 hours, is separated out dark red
Color solid, obtains final product.
Embodiment 2：
Compound for improving implantation body's anti-infection ability of the present invention is aryl ruthenium complex, and its chemical name is
One chlorine of monochlor(in)ate, a pair of fluorination benzene -2- contracting N4- phenyl thiosemicarbazide monomethyl cumene closes ruthenium (II)；
Its structural formula is：
Its physicochemical property is：Kermesinus crystal, soluble in water and organic solvent.
One chlorine of monochlor(in)ate of the present invention, a pair of fluorination benzene -2- contracting N4- phenyl thiosemicarbazide monomethyl cumene closes ruthenium
(II) preparation method, it is comprised the following steps that：
Step one, by the hydrate ruthenium trichloride of the ruthenium weight content 37% of 70 weight portions and the purity 95% of 480 weight portions
γ-terpinene be dissolved in the dehydrated alcohol of 1500 weight portions, be heated to reflux stirring 6 hours, stand precipitation and obtain with formula (III)
Compound, i.e. dichloride-two-cymol closes two rutheniums (II)；
Step 2, weighs the N of 35 weight portions4The 4-Fluorobenzaldehyde of-phenyl thiosemicarbazide and 26 weight portions is dissolved in 910 jointly
The dehydrated alcohol of weight portion, is heated to 70 DEG C, after 4 hours, stands precipitation and obtains the compound with formula (IV), i.e., to fluorobenzene first
Al benzene is for thiosemicarbazides；
Step 3, by the 4-Fluorobenzaldehyde contracting benzene of 5.5 weight portions for thiosemicarbazides and 6 weight portions dichloride-two-
Cymol closes the dichloromethane that two rutheniums (II) are dissolved in 1250 weight portions, and room temperature 22-25 DEG C is stirred 3 hours, is separated out dark red
Color solid, obtains final product.
Embodiment 3：
Compound for improving implantation body's anti-infection ability of the present invention is aryl ruthenium complex, and its chemical name is
One chlorine of monochlor(in)ate, a pair of fluorination benzene -2- contracting N4- phenyl thiosemicarbazide monomethyl cumene closes ruthenium (II)；
Its structural formula is：
Its physicochemical property is：Kermesinus crystal, soluble in water and organic solvent.
One chlorine of monochlor(in)ate of the present invention, a pair of fluorination benzene -2- contracting N4- phenyl thiosemicarbazide monomethyl cumene closes ruthenium
(II) preparation method, it is comprised the following steps that：
Step one, by the hydrate ruthenium trichloride of the ruthenium weight content 37% of 69 weight portions and the purity 95% of 478 weight portions
γ-terpinene be dissolved in the dehydrated alcohol of 1480 weight portions, be heated to reflux stirring 6 hours, stand precipitation and obtain with formula (III)
Compound, i.e. dichloride-two-cymol closes two rutheniums (II)；
Step 2, weighs the N of 31 weight portions4The 4-Fluorobenzaldehyde of-phenyl thiosemicarbazide and 23 weight portions is dissolved in 888 jointly
The dehydrated alcohol of weight portion, is heated to 70 DEG C, after 4 hours, stands precipitation and obtains the compound with formula (IV), i.e., to fluorobenzene first
Al benzene is for thiosemicarbazides；
Step 3, by the 4-Fluorobenzaldehyde contracting benzene of 5.1 weight portions for thiosemicarbazides and 6 weight portions dichloride-two-
Cymol closes the dichloromethane that two rutheniums (II) are dissolved in 1244 weight portions, and room temperature 22-25 DEG C is stirred 3 hours, is separated out dark red
Color solid, obtains final product.
As shown in figure 1, its hydrogen nuclear magnetic resonance modal data is1HNMR(CDCl3Solvent)：δ：8.903 (1H, s, CH=N),
8.429-8.382 (2H, m, phenyl-H), 7.505-7.424 (7H, m, phenyl-H), 5.765 (1H, d, J=6.0Hz, p-
Cym phenyl-H), 5.202 (1H, d, J=5.9Hz, p-cym phenyl-H), 5.092 (1H, d, J=6.0Hz, p-cym
Phenyl-H), 5.046 (1H, d, J=6.0Hz, p-cym phenyl-H), 2.713-2.621 (1H, m, p-cym CH
(CH3)2), 2.117 (3H, s, p-cym CCH3), 1.224 (3H, d, J=6.9Hz, p-cym CH (CH3)2), 1.165 (3H, d, J
=6.9Hz, p-cym CH (CH3)2)ppm.。
Its pharmaceutically active and its application are further illustrated below by pharmacodynamic experiment.
Experiment one：Antibacterial ability is tested：
1mL concentration is added to be 10 in sterilizing test tubes6The bacterium solution of/ml, the Organometallic ruthenium for adding 1mg embodiments 3 to obtain
Ion-pair compound, 37 DEG C of culture 24h.After cultivating time point, culture medium is collected uses doubling dilution, and extension rate is 10
Times and spread plate method detect viable count.Result of the test shows：Product is to staphylococcus aureuses (ATCC by obtained in the present invention
6538), colon bacillus (ATCC 25922), candida albicans (ATCC 10231), Bacillus subtilis endophyticus
(ATCC 9372) all has very strong bactericidal properties, and its sterilizing rate is up to more than 99.999%.
Experiment two：Activity of osteoblast proliferation is tested：
The aryl ruthenium complex 1mg that embodiment 3 is obtained is placed in 24 orifice plates, and 1ml density is 2 × 104The mice of/ml into
Then osteocyte suspension inoculation is cultivated 1,4 and 7 days in 24 orifice plates.To after predetermined point of time, the MTT of 200 μ l is added per hole
(5mg/ml) with 800 μ l serum-frees without phenol red DMEM.37 DEG C of incubations are inhaled after 4 hours and abandon supernatant, add 1ml dimethyl sulfoxide
(DMSO) crystal that dissolving is generated, takes three part of 200 μ l lysate and goes to 96 well culture plates per hole, with spectrophotometer in
Its OD value is surveyed at 490nm.As a result show, as shown in Fig. 2 one chlorine of monochlor(in)ate of the present invention, a pair of fluorination benzene -2- contracting N4- phenylamino
Base thiourea monomethyl cumene closes ruthenium (II) and shows obvious cell-proliferation activity.
Experiment three：Initial cell differentiation capability is analyzed：
By alkali phosphatase (ALP) activity for comparing the product of the present invention as the initial differentiation marker of osteoblast,
Check the impact that product of the present invention breaks up to mouse bone-forming cell.For relatively more osteoblastic differentiation capability, it is by 1ml density
2×104The mouse bone-forming cell of/ml is inoculated in 24 orifice plates, and is cultivated 1 day.Subsequently, respectively with the training without product of the present invention
Foster base and the division culture medium containing 1mg products of the present invention process cell, and containing 5%CO237 DEG C of calorstats in cultivate,
The 7th day and the 14th day measurement ALP is active after culture.Experiment finds, as shown in figure 3, the ALP that product of the present invention showed at the 14th day
Activity is higher than culture medium by 46%, and this shows that osteoblast differentiation ability is obviously improved.
Experiment four：Cytotoxicity analysis：
It is big the cytotoxicity of product of the present invention to be assessed using the activity of lactic acid dehydrogenase (LDH) as cytotoxicity index
It is little.It is 1 × 10 by concentration4The mouse bone-forming cell of individual cell is inoculated in 24 orifice plates, and is cultivated 1 day.Subsequently, respectively with not containing
The culture medium of product of the present invention and the division culture medium containing 1mg products of the present invention process cell, and containing CO237 DEG C of constant temperature
Cultivate 24 hours in case, supernatant is taken after centrifugation for LDH activity detection.Experimental result is as shown in the table.
| Culture medium | Product of the present invention | |
| LDH activity | 308 | 293 |
Can be shown by upper table, the compound Jing cell toxicity test tables for improving implantation body's anti-infection ability of the present invention
Bright, the LDH activity containing product free medium of the present invention is 293, and the culture medium 308 slightly below without product of the present invention illustrates this
Invention product is nontoxic.
Although embodiment of the present invention is disclosed as above, it is not restricted to listed in description and embodiment
With, it can be applied to completely various suitable the field of the invention, for those skilled in the art, can be easily
Other modification is realized, therefore under the general concept limited without departing substantially from claim and equivalency range, the present invention is not limited
In specific details and shown here as the embodiment with description.
Claims (1)
1. a kind of purposes for improving the compound of implantation body's anti-infection ability, the structural formula of the compound is formula (I)
Characterized in that, for preparing the medicine for improving implantation body's anti-infection ability, the medicine has antibacterial and promotes skeletonization thin
Intracellular growth function.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410513757.0A CN104277076B (en) | 2014-09-29 | 2014-09-29 | Compound for enhancing anti-infection capacity of plants, and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410513757.0A CN104277076B (en) | 2014-09-29 | 2014-09-29 | Compound for enhancing anti-infection capacity of plants, and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104277076A CN104277076A (en) | 2015-01-14 |
| CN104277076B true CN104277076B (en) | 2017-04-12 |
Family
ID=52252469
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410513757.0A Active CN104277076B (en) | 2014-09-29 | 2014-09-29 | Compound for enhancing anti-infection capacity of plants, and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104277076B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105288745B (en) * | 2015-11-17 | 2018-06-22 | 广西中医药大学 | The preparation method of titania nanotube with antibacterial anticancer |
| CN105288726B (en) * | 2015-11-17 | 2018-06-22 | 广西中医药大学 | Titanium metal material of ruthenium complex modification and its preparation method and application |
| CN105412982B (en) * | 2015-11-17 | 2018-06-22 | 广西中医药大学 | A kind of method for improving titania nanotube antibacterial and antitumaous effect |
| CN105251054B (en) * | 2015-11-17 | 2018-06-22 | 广西中医药大学 | The method that the titania nanotube with antibacterial anticancer is prepared using ruthenium complex |
| CN105239068B (en) * | 2015-11-17 | 2017-11-03 | 广西中医药大学 | Stainless steel material of ruthenium complex modification and preparation method thereof and purposes |
| CN105457088B (en) * | 2015-11-20 | 2018-04-03 | 广西中医药大学 | A kind of method for preparing the titanium with antibacterial anti-cancer properties |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103113414A (en) * | 2013-03-06 | 2013-05-22 | 广西中医药大学 | Aryl ruthenium complex, preparation method and application thereof |
-
2014
- 2014-09-29 CN CN201410513757.0A patent/CN104277076B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN104277076A (en) | 2015-01-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104277076B (en) | Compound for enhancing anti-infection capacity of plants, and preparation method and application thereof | |
| Aridoss et al. | A facile synthesis, antibacterial, and antitubercular studies of some piperidin-4-one and tetrahydropyridine derivatives | |
| CN105801670B (en) | Have polypeptide and its application of antibacterial activity | |
| Sharma et al. | Synthesis of β-ionone derived chalcones as potent antimicrobial agents | |
| Üstün et al. | Synthesis, characterization, antimicrobial and antibiofilm activity, and molecular docking analysis of NHC precursors and their Ag-NHC complexes | |
| Lakshmi et al. | Anticancer potentials of secondary metabolites from endophytes of Barringtonia acutangula and its molecular characterization | |
| Koran et al. | Synthesis, characterization, and biological evaluation of new oxime-phosphazenes | |
| Raimondi et al. | Synthesis and anti-staphylococcal activity of new 4-diazopyrazole derivatives | |
| Peeters et al. | Modulation of the substitution pattern of 5-aryl-2-aminoimidazoles allows fine-tuning of their antibiofilm activity spectrum and toxicity | |
| CN109503562B (en) | 2- [4- (2-thienyl) ] pyrimidyl urea derivative and preparation method and application thereof | |
| CN104311600B (en) | A kind of to fluorophenyl-2-contracting N4-phenyl thiosemicarbazide aryl ruthenium complex and its production and use | |
| CN106038565A (en) | Application of hanfangichin A and hanfangichin B in resisting drug-resistance bacterium activity | |
| CN109942561A (en) | 4- (2- thienyl) pyrimidine derivatives and its preparation method and application | |
| CN105622492B (en) | Chalcone derivative with antimicrobial agent activity | |
| Reddy et al. | Synthesis of novel amide functionalized 2H-chromene derivatives by Ritter amidation of primary alcohol using HBF4· OEt2 as a mild and versatile reagent and evaluation of their antimicrobial and anti-biofilm activities | |
| CN110368396A (en) | The new application of retrovir | |
| US6395773B1 (en) | Anti-drug resistant strain agents and antichlamydia agents | |
| CN104472505B (en) | A kind of mould inhibitor and application thereof | |
| CN102464603B (en) | Isatin derivative and application thereof in preparation of medicines for resisting super-drug-resistance bacteria | |
| CN109535136A (en) | 2- [4- (2- furyl)] pyrimidine radicals carbamide compounds and its preparation method and application | |
| CN106083726B (en) | Unsymmetrical disulfide class compound containing cyclohexyl and its purposes in antibacterials are prepared | |
| CN107089978A (en) | Thiazolidinone derivatives and its production and use | |
| Dong et al. | Synthesis, Characterization, and Antimicrobial Evaluation of Random Poly (ester-Carbonate) s Bearing Pendant Primary Amine in the Main Chain | |
| CN104738097A (en) | Beauveria bassiana barrel mixed agent and preparation method thereof | |
| CN104725332A (en) | Chalcone thiazole amide compound and preparation method and applications thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20210201 Address after: 710000 Shaanxi Xi'an economic and Technological Development Zone, Fengcheng four road, Ming Guang road, southeast corner of the new business building 1808 Patentee after: SHAANXI ZHUANYI INTELLECTUAL PROPERTY OPERATION Co.,Ltd. Address before: 530213 No. 13 Wuhe Avenue, Qingxiu District, Nanning City, Guangxi Zhuang Autonomous Region Patentee before: Guangxi University of Chinese Medicine |
|
| TR01 | Transfer of patent right |