CN106279291B - It is a kind of to contain naphthalene carboxyphenyl and Phen and the double-core manganese complex of hydrone and the preparation method and application thereof - Google Patents
It is a kind of to contain naphthalene carboxyphenyl and Phen and the double-core manganese complex of hydrone and the preparation method and application thereof Download PDFInfo
- Publication number
- CN106279291B CN106279291B CN201610662765.0A CN201610662765A CN106279291B CN 106279291 B CN106279291 B CN 106279291B CN 201610662765 A CN201610662765 A CN 201610662765A CN 106279291 B CN106279291 B CN 106279291B
- Authority
- CN
- China
- Prior art keywords
- phen
- carboxyphenyl
- double
- hydrone
- naphthalene
- 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
- 239000011572 manganese Substances 0.000 title claims abstract description 51
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 title claims abstract description 49
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 title claims abstract description 48
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 title claims abstract description 46
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 title claims abstract description 43
- 229910052748 manganese Inorganic materials 0.000 title claims abstract description 43
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 239000013078 crystal Substances 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 16
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 claims description 13
- 201000007270 liver cancer Diseases 0.000 claims description 11
- 208000014018 liver neoplasm Diseases 0.000 claims description 11
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 10
- 229940071125 manganese acetate Drugs 0.000 claims description 10
- UOGMEBQRZBEZQT-UHFFFAOYSA-L manganese(2+);diacetate Chemical compound [Mn+2].CC([O-])=O.CC([O-])=O UOGMEBQRZBEZQT-UHFFFAOYSA-L 0.000 claims description 10
- 206010006187 Breast cancer Diseases 0.000 claims description 9
- 238000002425 crystallisation Methods 0.000 claims description 9
- 230000008025 crystallization Effects 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 208000026310 Breast neoplasm Diseases 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 230000001093 anti-cancer Effects 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 7
- 238000002447 crystallographic data Methods 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 238000010992 reflux Methods 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 201000005202 lung cancer Diseases 0.000 claims description 5
- 208000020816 lung neoplasm Diseases 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 claims 1
- -1 carboxyphenyl Chemical group 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 abstract description 10
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 10
- 210000004027 cell Anatomy 0.000 description 27
- 238000012360 testing method Methods 0.000 description 10
- 238000000921 elemental analysis Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 201000005296 lung carcinoma Diseases 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000003560 cancer drug Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 150000005041 phenanthrolines Chemical class 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- USZZLTVYRPLBMB-UHFFFAOYSA-N 1,3-dihydroxynaphthalene-2-carboxylic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=C(O)C=C21 USZZLTVYRPLBMB-UHFFFAOYSA-N 0.000 description 1
- 125000000972 4,5-dimethylthiazol-2-yl group Chemical group [H]C([H])([H])C1=C(N=C(*)S1)C([H])([H])[H] 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- 208000030136 Marchiafava-Bignami Disease Diseases 0.000 description 1
- 208000029725 Metabolic bone disease Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 201000008274 breast adenocarcinoma Diseases 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 150000004699 copper complex Chemical class 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000004251 human milk Anatomy 0.000 description 1
- 235000020256 human milk Nutrition 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- RMHJJUOPOWPRBP-UHFFFAOYSA-N naphthalene-1-carboxamide Chemical compound C1=CC=C2C(C(=O)N)=CC=CC2=C1 RMHJJUOPOWPRBP-UHFFFAOYSA-N 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 239000005648 plant growth regulator Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 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
- C07F13/00—Compounds containing elements of Groups 7 or 17 of the Periodic Table
- C07F13/005—Compounds without a metal-carbon linkage
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
It is disclosed by the invention a kind of containing naphthalene carboxyphenyl and Phen and the double-core manganese complex of hydrone and the preparation method and application thereof, it is the complex of following structure formula (I).The invention also discloses the preparation methods and application in preparation of anti-tumor drugs of the double-core manganese complex containing naphthalene carboxyphenyl and Phen and hydrone.
Description
Technical field
The present invention relates to a kind of double-core manganese complex containing naphthalene carboxyphenyl Yu Phen and hydrone, and its preparation side
Method, and should containing naphthalene carboxyphenyl with the double-core manganese complex of Phen and hydrone answering in the preparation of antitumor drugs
With.
Background technique
Phen has the potential with DNA effect, the mode of action is mainly three kinds different as planar molecule
Non-covalent fashion: Groove binding, insertion combine and insertion combines；In addition, there are also electrostatical binding and hydrogen bond, ionic bond, models
The weak interactions such as De Huali and hydrophobic bond.These effects can often induce many biological effects, hinder the normal of information nucleic acid
Expression, to have the potential for inhibiting the duplication anticancer of DNA antitumor.It is reported that Phen has sterilization and fluorescence
Matter has been widely used in preparing fields (the Senthil K.R, et such as macromolecular bioprobe, luminescent material and antibacterial
Al., Polyhedron2008,27:1111).Naphthoic acid is used as organic synthesis intermediate and plant growth regulator, and its derivative
Object shows good bioactivity.
Chinese patent CN 1312285C discloses the preparation method and Isosorbide-5-Nitrae-of 1,4-dihydroxy-2-naphthsaisyuoic acid
Dihydroxy-2-naphthoic acid composition helps to improve intestinal flora, alleviation abdominal discomfort relevant to intake milk and prevent
Metabolic bone disease.
101687801 B of Chinese patent CN discloses the ether of the naphthoic acid amide as treatment of cancer.
102146088 A of Chinese patent CN discloses 1, the 10- Phen that a kind of unit replaces or multidigit replaces and spreads out
Biological copper complex and preparation method thereof and such complex are in the drug that preparation prevents and treats cancer and tumor disease
Application.
The transition metal copper (II) that 103193801 B of Chinese patent CN discloses a ligand containing derivative of phenanthroline is matched
The interaction of object and DNA is closed, and to the antitumor Journal of Sex Research while still alive of human cervical carcinoma cell.
101721411 B of Chinese patent CN disclose derivative of phenanthroline or its pharmaceutically acceptable salt is being made
It is standby to prevent or treat the application in liver-cancer medicine.
It is the experiment proved that the substance with preferable bioactivity, the present invention select naphthalene first based on Phen and naphthoic acid
Acid and Phen are ligand, are reacted under certain condition with manganese acetate, and synthesis has been obtained to NCI-H460(human lung carcinoma cell),
MCF7(people's breast adenocarcinoma cell), HEPG2(human liver cancer cell) the stronger complex of inhibitory activity, for exploitation anticancer drug mention
New way is supplied.
Summary of the invention
In view of the above-mentioned problems of the prior art, the first object of the present invention there is provided one kind containing naphthalene carboxyphenyl with
The double-core manganese complex of Phen and hydrone.
The second object of the present invention is to provide the above-mentioned double-core manganese containing naphthalene carboxyphenyl and Phen and hydrone and cooperates
The preparation method of object.
Third mesh of the invention is to provide the above-mentioned double-core manganese complex containing naphthalene carboxyphenyl Yu Phen and hydrone
Preparing the application in anticancer drug.
As a kind of double-core manganese complex containing naphthalene carboxyphenyl Yu Phen and hydrone of first aspect present invention,
It is the complex of following structure formula (I):
(I)。
Double-core manganese complex containing naphthalene carboxyphenyl and Phen and hydrone of the invention is through elemental analysis, infrared light
Spectrum analysis and x-ray crystal structure analysis, as a result as follows:
Elemental analysis (C68H46Mn2N4O9): theoretical value: C, 69.63；H, 3.95；N, 4.78.Measured value: C, 69.68；H,
4.01；N, 4.71.
IR(KBr, cm-1): 3427.51 (w), 3049.46 (m), 3012.81 (w), 2708.06 (w), 1942.36 (w),
1600.92 (s), 1589.34 (s), 1506.41 (m), 1456.26 (m), 1425.40 (m), 1398.39 (m), 1371.39 (m),
1344.38 (m), 1251.80 (m), 1217.08 (m), 1143.79 (m), 1101.35 (m), 1010.70 (m), 981.77 (w),
846.75 (s), 796.60 (s), 756.10 (s), 725.23 (s), 651.94 (s), 584.43 (m), 530.42 (m), 511.14
(m), 472.56 (w), 420.48 (m).
A kind of double-core manganese complex containing naphthalene carboxyphenyl and Phen and hydrone of the invention is crystal structure,
Crystallographic data: crystal category anorthic system, space groupP ,a=1.21754 (16) nm,b=1.33045 (17) nm,c=1.6572
(2) nm,α=83.624 (2) °,β=87.594 (2) °,γ=86.882 (2) °,Z=2, V=2.6622 (6) nm3,Dc=
1.463Mg·m-3,μ(MoKa)= 0.543mm-1,F(000)=1208,1.87 ° of <θ25.00 ° of <, crystalline size: 0.17 x
0.15 x 0.14mm,R=0.0299,wR=0.0792。
Being structurally characterized in that containing naphthalene carboxyphenyl and the double-core manganese complex of Phen and hydrone of the invention: molecule
In two Mn atoms formd respectively with four oxygen atoms and two nitrogen-atoms hexa-coordinate distortion octoploids structure.
A kind of double-core manganese complex containing naphthalene carboxyphenyl Yu Phen and hydrone as second aspect of the present invention
Preparation method, sequentially add naphthoic acid, Phen, manganese acetate and etoh solvent in order in the reaction vessel, stirring
Reflux is lower to react 8~12h；Cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains the transparent crystalline substance of brown color
Body, as the double-core manganese complex containing naphthalene carboxyphenyl Yu Phen and hydrone.
In a preferred embodiment of the invention, the naphthoic acid, Phen, manganese acetate three the mass ratio of the material
For 2:1:(1 ~ 1.4).
In a preferred embodiment of the invention, the etoh solvent dosage is that every mM of naphthoic acid adds 20 ~ 35 millis
It rises.
A kind of double-core manganese complex containing naphthalene carboxyphenyl Yu Phen and hydrone as third aspect present invention
Preparing the application in anticancer drug.
Applicant has carried out anti tumor activity in vitro confirmation research to above-mentioned complex, confirms that the complex has centainly
Anti-tumor biological, that is to say, that the purposes of above-mentioned complex is application in preparation of anti-tumor drugs, specifically
It is to prepare anti-human lung-cancer medicament, human breast carcinoma, the application in human liver cancer drug.
Double-core manganese complex containing naphthalene carboxyphenyl and Phen and hydrone of the invention is to human lung cancer drug, human milk
Gland cancer, human liver cancer drug etc. show good anticancer activity, can prepare anti-lung cancer, anti-breast cancer, anti-liver cancer and anti-using it as raw material
Drug, the double-core manganese complex of the invention containing naphthalene carboxyphenyl and Phen and hydrone have anticancer activity height, cost
Low, the features such as preparation method is simple, provides new way for exploitation anticancer drug.
Detailed description of the invention
Fig. 1 is the crystal molecular structure figure of the double-core manganese complex containing naphthalene carboxyphenyl and Phen and hydrone.
Fig. 2 is the IR spectrogram of the double-core manganese complex containing naphthalene carboxyphenyl and Phen and hydrone.
Fig. 3 is the TG-DTG curve of the double-core manganese complex containing naphthalene carboxyphenyl and Phen and hydrone.
Specific embodiment
By following embodiment, present invention be described in more detail, but should be noted that the scope of the present invention is not implemented by these
Any restrictions of example.
Embodiment 1:
The preparation of double-core manganese complex containing naphthalene carboxyphenyl and Phen and hydrone:
Sequentially add naphthoic acid 0.1721g (1mmol), Phen 0.0903g in order in 100ml round-bottomed flask
(0.5mmol), manganese acetate 0.0861(0.5mmol), etoh solvent 20mL is being stirred at reflux lower reaction 8h；It is cooling, filtering,
Control solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtain brown color transparent crystal, as containing naphthalene carboxyphenyl and Phen with
The double-core manganese complex of hydrone.Yield: 81%, fusing point: 150-151 DEG C.
Elemental analysis (C68H46Mn2N4O9): theoretical value: C, 69.63；H, 3.95；N, 4.78.Measured value: C, 69.68；H,
4.01；N, 4.71.
IR(KBr, cm-1): 3427.51 (w), 3049.46 (m), 3012.81 (w), 2708.06 (w), 1942.36 (w),
1600.92 (s), 1589.34 (s), 1506.41 (m), 1456.26 (m), 1425.40 (m), 1398.39 (m), 1371.39 (m),
1344.38 (m), 1251.80 (m), 1217.08 (m), 1143.79 (m), 1101.35 (m), 1010.70 (m), 981.77 (w),
846.75 (s), 796.60 (s), 756.10 (s), 725.23 (s), 651.94 (s), 584.43 (m), 530.42 (m), 511.14
(m), 472.56 (w), 420.48 (m).
Its crystallographic data: crystal category anorthic system, space groupP ,a=1.21754 (16) nm,b=1.33045 (17) nm,c=1.6572 (2) nm,α=83.624 (2) °,β=87.594 (2) °,γ=86.882 (2) °,Z=2, V=2.6622 (6) nm3,Dc=
1.463Mg·m-3,μ(MoKa)= 0.543mm-1,F(000)=1208,1.87 ° of <θ25.00 ° of <, crystalline size: 0.17 x
0.15 x 0.14mm,R=0.0299,wR=0.0792。
Embodiment 2:
The preparation of double-core manganese complex containing naphthalene carboxyphenyl and Phen and hydrone:
Sequentially add naphthoic acid 0.1725g (1mmol), Phen 0.0906g in order in 100ml round-bottomed flask
(0.5mmol), manganese acetate 0.1215(0.7mmol), etoh solvent 35mL is being stirred at reflux lower reaction 10h；It is cooling, filtering,
Control solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtain brown color transparent crystal, as containing naphthalene carboxyphenyl and Phen with
The double-core manganese complex of hydrone.Yield: 82%, fusing point: 150-151 DEG C.
Elemental analysis (C68H46Mn2N4O9): theoretical value: C, 69.63；H, 3.95；N, 4.78.Measured value: C, 69.68；H,
4.01；N, 4.71.
IR(KBr, cm-1): 3427.51 (w), 3049.46 (m), 3012.81 (w), 2708.06 (w), 1942.36 (w),
1600.92 (s), 1589.34 (s), 1506.41 (m), 1456.26 (m), 1425.40 (m), 1398.39 (m), 1371.39 (m),
1344.38 (m), 1251.80 (m), 1217.08 (m), 1143.79 (m), 1101.35 (m), 1010.70 (m), 981.77 (w),
846.75 (s), 796.60 (s), 756.10 (s), 725.23 (s), 651.94 (s), 584.43 (m), 530.42 (m), 511.14
(m), 472.56 (w), 420.48 (m).
Its crystallographic data: crystal category anorthic system, space groupP ,a=1.21754 (16) nm,b=1.33045 (17) nm,c=1.6572 (2) nm,α=83.624 (2) °,β=87.594 (2) °,γ=86.882 (2) °,Z=2, V=2.6622 (6) nm3,Dc=
1.463Mg·m-3,μ(MoKa)= 0.543mm-1,F(000)=1208,1.87 ° of <θ25.00 ° of <, crystalline size: 0.17 x
0.15 x 0.14mm,R=0.0299,wR=0.0792。
Embodiment 3:
The preparation of double-core manganese complex containing naphthalene carboxyphenyl and Phen and hydrone:
Sequentially add naphthoic acid 0.3449g (2mmol), Phen 0.1804g in order in 100ml round-bottomed flask
(1mmol), manganese acetate 0.1736(1mmol), etoh solvent 45mL is being stirred at reflux lower reaction 10h；It is cooling, filtering, 20 ~
Solvent volatilization crystallization is controlled under conditions of 35 DEG C, brown color transparent crystal is obtained, as containing naphthalene carboxyphenyl and Phen and water
The double-core manganese complex of molecule.Yield: 80%, fusing point: 150-151 DEG C.
Elemental analysis (C68H46Mn2N4O9): theoretical value: C, 69.63；H, 3.95；N, 4.78.Measured value: C, 69.68；H,
4.01；N, 4.71.
IR(KBr, cm-1): 3427.51 (w), 3049.46 (m), 3012.81 (w), 2708.06 (w), 1942.36 (w),
1600.92 (s), 1589.34 (s), 1506.41 (m), 1456.26 (m), 1425.40 (m), 1398.39 (m), 1371.39 (m),
1344.38 (m), 1251.80 (m), 1217.08 (m), 1143.79 (m), 1101.35 (m), 1010.70 (m), 981.77 (w),
846.75 (s), 796.60 (s), 756.10 (s), 725.23 (s), 651.94 (s), 584.43 (m), 530.42 (m), 511.14
(m), 472.56 (w), 420.48 (m).
Its crystallographic data: crystal category anorthic system, space groupP ,a=1.21754 (16) nm,b=1.33045 (17) nm,c=1.6572 (2) nm,α=83.624 (2) °,β=87.594 (2) °,γ=86.882 (2) °,Z=2, V=2.6622 (6) nm3,Dc=
1.463Mg·m-3,μ(MoKa)= 0.543mm-1,F(000)=1208,1.87 ° of <θ25.00 ° of <, crystalline size: 0.17 x
0.15 x 0.14mm,R=0.0299,wR=0.0792。
Embodiment 4:
The preparation of double-core manganese complex containing naphthalene carboxyphenyl and Phen and hydrone:
Sequentially add naphthoic acid 0.3449g (2mmol), Phen 0.1804g in order in 100ml round-bottomed flask
(1mmol), manganese acetate 0.1908(1.1mmol), etoh solvent 60mL is being stirred at reflux lower reaction 12h；It is cooling, filtering, 20
Solvent volatilization crystallization is controlled under conditions of ~ 35 DEG C, brown color transparent crystal is obtained, as containing naphthalene carboxyphenyl and Phen and water
The double-core manganese complex of molecule.Yield: 81%, fusing point: 150-151 DEG C.
Elemental analysis (C68H46Mn2N4O9): theoretical value: C, 69.63；H, 3.95；N, 4.78.Measured value: C, 69.68；H,
4.01；N, 4.71.
IR(KBr, cm-1): 3427.51 (w), 3049.46 (m), 3012.81 (w), 2708.06 (w), 1942.36 (w),
1600.92 (s), 1589.34 (s), 1506.41 (m), 1456.26 (m), 1425.40 (m), 1398.39 (m), 1371.39 (m),
1344.38 (m), 1251.80 (m), 1217.08 (m), 1143.79 (m), 1101.35 (m), 1010.70 (m), 981.77 (w),
846.75 (s), 796.60 (s), 756.10 (s), 725.23 (s), 651.94 (s), 584.43 (m), 530.42 (m), 511.14
(m), 472.56 (w), 420.48 (m).
Its crystallographic data: crystal category anorthic system, space groupP ,a=1.21754 (16) nm,b=1.33045 (17) nm,c=1.6572 (2) nm,α=83.624 (2) °,β=87.594 (2) °,γ=86.882 (2) °,Z=2, V=2.6622 (6) nm3,Dc=
1.463Mg·m-3,μ(MoKa)= 0.543mm-1,F(000)=1208,1.87 ° of <θ25.00 ° of <, crystalline size: 0.17 x
0.15 x 0.14mm,R=0.0299,wR=0.0792。
Embodiment 5:
The preparation of double-core manganese complex containing naphthalene carboxyphenyl and Phen and hydrone:
Sequentially add naphthoic acid 0.3449g (2mmol), Phen 0.1804g in order in 100ml round-bottomed flask
(1mmol), manganese acetate 0.2427(1.4mmol), etoh solvent 70mL is being stirred at reflux lower reaction 12h；It is cooling, filtering, 20
Solvent volatilization crystallization is controlled under conditions of ~ 35 DEG C, brown color transparent crystal is obtained, as containing naphthalene carboxyphenyl and Phen and water
The double-core manganese complex of molecule.Yield: 83%, fusing point: 150-151 DEG C.
Elemental analysis (C68H46Mn2N4O9): theoretical value: C, 69.63；H, 3.95；N, 4.78.Measured value: C, 69.68；H,
4.01；N, 4.71.
IR(KBr, cm-1): 3427.51 (w), 3049.46 (m), 3012.81 (w), 2708.06 (w), 1942.36 (w),
1600.92 (s), 1589.34 (s), 1506.41 (m), 1456.26 (m), 1425.40 (m), 1398.39 (m), 1371.39 (m),
1344.38 (m), 1251.80 (m), 1217.08 (m), 1143.79 (m), 1101.35 (m), 1010.70 (m), 981.77 (w),
846.75 (s), 796.60 (s), 756.10 (s), 725.23 (s), 651.94 (s), 584.43 (m), 530.42 (m), 511.14
(m), 472.56 (w), 420.48 (m).
Its crystallographic data: crystal category anorthic system, space groupP ,a=1.21754 (16) nm,b=1.33045 (17) nm,c=1.6572 (2) nm,α=83.624 (2) °,β=87.594 (2) °,γ=86.882 (2) °,Z=2, V=2.6622 (6) nm3,Dc=
1.463Mg·m-3,μ(MoKa)= 0.543mm-1,F(000)=1208,1.87 ° of <θ25.00 ° of <, crystalline size: 0.17 x
0.15 x 0.14mm,R=0.0299,wR=0.0792。
Test example:
Double-core manganese complex containing naphthalene carboxyphenyl Yu Phen and hydrone of the invention, Anticancer Activity in vitro are surveyed
It surely is realized by MTT experiment method.
MTT analyses method:
3- (4,5-Dimethylthiazol-2-yl) -2,5-diArenyltetrazolium is restored with metabolism
Based on bromide.Succinate dehydrogenase in living cells mitochondria can make exogenous MTT be reduced to the bluish violet of water-insoluble
Crystallization first a ceremonial jade-ladle, used in libation (Formazan) is simultaneously deposited in cell, and dead cell is without this function.Dimethyl sulfoxide (DMSO) can dissolve cell
In first a ceremonial jade-ladle, used in libation, with microplate reader measurement characteristic wavelength optical density, can reflect living cells quantity indirectly.
Matching containing naphthalene carboxyphenyl and the double-core manganese of Phen and hydrone for the preparation of embodiment 1 is measured using mtt assay
Object is closed to the inhibitory activity of human lung carcinoma cell (NCI-H460), human breast cancer cell (MCF7), human liver cancer cell (HepG2).
Cell strain and cultivating system: NCI-H460, MCF7 and HepG2 cell strain are derived from American tissue incubator (ATCC).
With contain 10% fetal calf serum RPMI1640 (GIBICO company) culture medium, in 5% (volume fraction) CO2, 37 DEG C of saturated humidity trainings
It supports and carries out in vitro culture in case.
Test process: test medical fluid (0.1nM-10uM) is added separately in each hole according to the concentration gradient of concentration,
Each concentration sets 3 parallel holes.Experiment is divided into drug test group (the test medicine for being separately added into various concentration), control group (only adds
Test medicine is not added in culture solution and cell) and blank group (only adding culture solution, cell and test medicine is not added).By the orifice plate after dosing
37 DEG C are placed in, 5%CO272h is cultivated in incubator.The activity of control drug is measured according to the method for test sample.It is cultivating
In orifice plate after 72h, every hole adds MTT40uL (being made into 4mg/mL with D-Hanks buffer).After 37 DEG C of placement 4h, remove
Clear liquid.Every hole adds 150uL DMSO, vibrates 5min, makes Formazan crystallization dissolution.Finally, using automatic microplate reader in 570nm
The optical density in each hole is detected at wavelength.
Data processing: data processing uses GraAr Pad Prism version5.0 program, compound IC50Pass through program
In be fitted to obtain with the nonlinear regression model (NLRM) of S-shaped dose response.
With MTT analytic approach to human lung carcinoma cell (NCI-H460) cell strain, human breast cancer cell (MCF7) cell strain, people liver
Cancer cell (HepG2) cell strain is analyzed, its IC is measured50Value, the results are shown in Table 1, conclusion are as follows: from the data in the table,
The double-core manganese complex for containing naphthalene carboxyphenyl and Phen and hydrone of the invention is as anticancer drug, to human lung cancer, people
Breast cancer, human liver cancer anticancer activity are higher, can be used as the candidate compound of anticancer drug.
Double-core manganese complex anticancer drug external activity test of the table 1 containing naphthalene carboxyphenyl Yu Phen and hydrone
Data
| Human lung carcinoma cell | Human breast cancer cell | Human liver cancer cell | |
| Cell strain | NCI-H460 | MC-7 | HEPG2 |
| IC50 μM | 2.77 | 3.07 | 3.73 |
The double-core manganese complex containing naphthalene carboxyphenyl and Phen and hydrone of remaining embodiment preparation is with mtt assay pair
The anticancer activity test method of human lung carcinoma cell (NCI-H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7)
Same test example, test result and table 1 are essentially identical.
Claims (4)
1. the double-core manganese complex of a kind of naphthalene carboxyphenyl and Phen and hydrone is the complex of following structure formula (I):
Its ir data: FT-IR (KBr, v/cm-1): 3427.51 (w), 3049.46 (m), 3012.81 (w), 2708.06
(w), 1942.36 (w), 1600.92 (s), 1589.34 (s), 1506.41 (m), 1456.26 (m), 1425.40 (m), 1398.39
(m), 1371.39 (m), 1344.38 (m), 1251.80 (m), 1217.08 (m), 1143.79 (m), 1101.35 (m), 1010.70
(m), 981.77 (w), 846.75 (s), 796.60 (s), 756.10 (s), 725.23 (s), 651.94 (s), 584.43 (m),
530.42 (m), 511.14 (m), 472.56 (w), 420.48 (m), wherein the manganese of the naphthalene carboxyphenyl and Phen cooperates
Object is crystal structure, and crystallographic data is as follows: anorthic system, space group P1, a=1.21754 (16) nm, b=1.33045
(17) nm, c=1.6572 (2) nm, α=83.624 (2) °, β=87.594 (2) °, γ=86.882 (2) °, Z=2, V=
2.6622(6)nm3；Two Mn atoms form the eight of hexa-coordinate distortion with four oxygen atoms and two nitrogen-atoms respectively in molecule
The double-core manganese complex of face body configuration, the naphthalene carboxyphenyl and Phen and hydrone is prepared by the following method:
Naphthoic acid, Phen, manganese acetate and etoh solvent are sequentially added in reaction vessel in order, be stirred at reflux it is lower reaction 8~
12h；Cooling, filtering controls solvent volatilization crystallization under conditions of 20~35 DEG C, obtains brown color transparent crystal, as contain naphthalene
The double-core manganese complex of carboxyphenyl and Phen and hydrone, the naphthoic acid, Phen, manganese acetate three substance
Amount is than being 2:1:(1~1.4).
2. the double-core manganese complex of naphthalene carboxyphenyl as described in claim 1 and Phen and hydrone, which is characterized in that institute
Stating etoh solvent dosage is that every mM of naphthoic acid adds 20~35 milliliters.
3. a kind of double-core manganese complex of naphthalene carboxyphenyl and Phen and hydrone as described in claim 1, which is characterized in that
It can be stabilized at 150 DEG C or less.
4. the double-core manganese complex of a kind of naphthalene carboxyphenyl as described in claim 1 and Phen and hydrone is in preparation anticancer
Application in drug, wherein the cancer cell is lung cancer, breast cancer, liver cancer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610662765.0A CN106279291B (en) | 2016-08-14 | 2016-08-14 | It is a kind of to contain naphthalene carboxyphenyl and Phen and the double-core manganese complex of hydrone and the preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610662765.0A CN106279291B (en) | 2016-08-14 | 2016-08-14 | It is a kind of to contain naphthalene carboxyphenyl and Phen and the double-core manganese complex of hydrone and the preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106279291A CN106279291A (en) | 2017-01-04 |
| CN106279291B true CN106279291B (en) | 2019-06-14 |
Family
ID=57669305
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610662765.0A Expired - Fee Related CN106279291B (en) | 2016-08-14 | 2016-08-14 | It is a kind of to contain naphthalene carboxyphenyl and Phen and the double-core manganese complex of hydrone and the preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106279291B (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105218586B (en) * | 2015-10-10 | 2017-10-17 | 衡阳师范学院 | A kind of manganese complex of contracted containing 3,5 Dibromosalicylaldehydes 4 nitro o-aminophenol Schiffs and pyridine and its preparation method and application |
-
2016
- 2016-08-14 CN CN201610662765.0A patent/CN106279291B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN106279291A (en) | 2017-01-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108358973A (en) | Naphthalimide tetravalence platinum-like compounds, preparation method and its application in preparation of anti-tumor drugs | |
| CN105198937B (en) | A kind of cobalt complex of contracted containing 3,5 dichloro-salicylaldehydes 4 nitro o-aminophenol Schiffs and pyridine and its preparation method and application | |
| CN106188128B (en) | A kind of Tricyclohexyltin 2- naphthoate complex and the preparation method and application thereof | |
| CN106317090A (en) | Cadmium complex containing naphthyl methyl carboxyl and phenanthroline and preparation method and application of cadmium complex | |
| CN106279291B (en) | It is a kind of to contain naphthalene carboxyphenyl and Phen and the double-core manganese complex of hydrone and the preparation method and application thereof | |
| CN105315310B (en) | A kind of nickel complex of contracted containing 3,5 dichloro-salicylaldehydes 4 chlorine o-aminophenol Schiffs and pyridine and its preparation method and application | |
| CN105198931B (en) | A kind of manganese complex of contracted containing 3,5 dichloro-salicylaldehydes 4 nitro o-aminophenol Schiffs and pyridine and its preparation method and application | |
| CN105315311B (en) | A kind of nickel complex of contracted containing 5 chloro-salicylic aldehydes 4 chlorine o-aminophenol Schiffs and pyridine and its preparation method and application | |
| CN106349483A (en) | Multicore calcium polymer containing naphthylcarboxymethyl and phenanthroline and preparation method and application thereof | |
| CN109627210B (en) | Gallium fluorescent probe, preparation method, application and application product thereof | |
| CN105218586B (en) | A kind of manganese complex of contracted containing 3,5 Dibromosalicylaldehydes 4 nitro o-aminophenol Schiffs and pyridine and its preparation method and application | |
| CN105218593B (en) | A kind of cobalt complex of contracted containing 3,5 Dibromosalicylaldehydes 4 nitro o-aminophenol Schiffs and pyridine and its preparation method and application | |
| CN105348328B (en) | A kind of nickel complex of contracted containing 3,5 dichloro-salicylaldehydes 4 nitro o-aminophenol Schiffs and pyridine and its preparation method and application | |
| CN106336430B (en) | A kind of ALPHA-ketobutyric acid p-nitrophenyl formyl hydrazone di-n-butyl tin complex and its preparation method and application | |
| CN107033181B (en) | A kind of chlorination Dibenzyltin dimethylglyoxime complex and the preparation method and application thereof | |
| CN107141315B (en) | A kind of di-n-butyl tin O-methoxy nicotinate complex and the preparation method and application thereof | |
| CN105315312B (en) | A kind of nickel complex of contracted containing 5 bromosalicylaldehydes 4 chlorine o-aminophenol Schiffs and pyridine and its preparation method and application | |
| CN105367607A (en) | Nickel complex containing 5-chlorosalicylaldehyde condensation 4-nitro o-aminophenol Schiff alkali and pyridine and preparation method and application of nickel complex | |
| CN107011375A (en) | A kind of double [chlorination two (o-chlorobenzyl) tin thiosalicylic acid butyl ester complexs] and preparation method and application | |
| CN106380480B (en) | A kind of ALPHA-ketobutyric acid p-nitrophenyl formyl hydrazone stannous phenide complex and its preparation method and application | |
| CN105218567A (en) | A kind of Zn complex containing 5-chloro-salicylic aldehyde contracting 4-nitro o-aminophenol Schiff and pyridine and its preparation method and application | |
| CN105218566A (en) | A kind of Zn complex containing 5-bromosalicylaldehyde contracting 4-nitro o-aminophenol Schiff and pyridine and its preparation method and application | |
| CN105837620A (en) | Chiral organotin carboxylate tris (2-methyl-2-phenyl ) propyl tin L-mandelate complex and preparation method and application thereof | |
| CN106279260B (en) | A kind of ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin complex and its preparation method and application | |
| CN106279261B (en) | A kind of di-n-butyl tin complex and its preparation method and application |
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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20190614 |