CN106220675B - A kind of stannous phenide complex of the ligand containing acylhydrazone and its preparation method and application - Google Patents
A kind of stannous phenide complex of the ligand containing acylhydrazone and its preparation method and application Download PDFInfo
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- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/22—Tin compounds
- C07F7/2284—Compounds with one or more Sn-N linkages
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
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- C07F7/2296—Purification, stabilisation, isolation
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Abstract
The invention discloses a kind of ALPHA-ketobutyric acids to tert-butyl benzoyl hydrazone stannous phenide complex, is the complex of following structure formula (I), wherein R is phenyl.The invention also discloses the ALPHA-ketobutyric acids to the preparation method of tert-butyl benzoyl hydrazone stannous phenide complex and to prepare the application in anticancer drug.
Description
Technical field
The present invention relates to a kind of ALPHA-ketobutyric acids to tert-butyl benzoyl hydrazone stannous phenide complex and preparation method thereof, with
And the ALPHA-ketobutyric acid is preparing the application in anticancer drug to tert-butyl benzoyl hydrazone stannous phenide complex.
Background technique
Organotin is a kind of metallo-organic compound containing Sn-C key.Researcher just notices before very early
The Anticancer Activity in vitro of organo-tin compound.The research of organotin (IV) antitumor activity of compound can be traced to nineteen twenty-nine.
1967, Kanisawa etc. thought that stannic chloride is invalid to the primary tumor of mouse and rat.But in 1972, Brown was had found,
Pass through food or drug administration by injection, triphenyltin acetate Ph3SnOOCCH3It can inhibit the tumour growth of mouse, and triphenyltin chloride
Then cannot.Between 1972 ~ 1977 years, Dutch scholar has studied a large amount of organo-tin compound, but finds no further screening valence
The compound of value.They continue deeper into research, finally found that the tin compound of two organic groups coordination, such as tin-oxide
(R2SnO), tin hydroxide [ SnR2(OH) X ] etc. have anti-tumor activity, and find out that they all contain or hydrolyze and can generate tin oxygen
Key.1986, Crowe etc. had found that some organo-tin compounds have preferable anticancer activity again, anti-about organotin from this
The active research of cancer becomes the another extremely active hot spot after cis-platinum.1989, American National anticancer research institute
(National Cancer Institute) has carried out antitumor activity screening to more than 2,000 kinds of organo-tin compounds, as a result table
Bright some organo-tin compounds have inhibiting effect to P388 lymphocytic leukemia.2002, Gielen et al. was to organic
The activity of tin carboxylate compound has done comprehensive summing up, and many organo-tin compounds are thought after research really has preferably in vitro
Anticancer activity.
Studies have shown that the organic group connected on organic tin atom and the ligand for participating in being coordinated decide organo-tin compound
Bioactivity, select it is some itself with the active organic ligand of good biological in organotin tin atoms be coordinated causes
The great interest of people.Acylhydrazone is one kind Schiff compound made of being modified as hydrazide kind compound, they
It is condensed by aldehydes or ketones and hydrazides, there is the bond type similar with peptide bond in molecule, there is good bioactivity, stronger match
Capability and multiplicity coordination mode, and medicine, pesticide, material and in terms of have a wide range of applications.Closely
Nian Lai, domestic and international many researchers compare it in terms of bioactivity in depth to be studied, and research finds acylhydrazone class
Compound has the various actives such as anticancer, sterilization, anti-inflammatory.Therefore, by acylhydrazone class Schiff ligand in conjunction with organotin, it is intended to
The stronger noval chemical compound of bioactivity is obtained, the interested research direction of people is become.
Chinese patent CN 102718794A discloses a kind of double acylhydrazone class Schiff stannous phenide complexs and its is making
Standby Antilung gland cancer, colon cancer, leukaemia cell drug in application.
Chinese patent CN 101851251A disclose a kind of acylhydrazone class Schiff ligand dibutyl tin complex and its
Application in the drug of preparation treatment liver cancer, adenocarcinoma of lung, breast cancer, prostate cancer, colon cancer or early young grain leukaemia.
Document (Journal of Organometallic Chemistry, 2014,75:It 83-91) reports, organotin
Acylhydrazone class Schiff base complex is thin to human colon cancer cell (HCT-116), human lung adenocarcinoma cell (A549), human umblilical vein endothelial
Born of the same parents (HUVEC) have compared with strong biological activity, and are better than carboplatin.
Document (Journal of Organometallic Chemistry, 2013,724:It 23-31) reports, series has
Machine tin acylhydrazone class Schiff base complex, organo-tin compound and acylhydrazone class Schiff ligand are respectively to human lung adenocarcinoma cell
(A549), the inhibiting effect of the cancer cells such as human colon cancer cell (HCT-8), people in loop (hl-60).
Document (Bioorganic & Medicinal Chemistry Letters, 2015,25: 4461- 4463)
Report, anticancer activity of a variety of acylhydrazone class Schiff ligands to human liver cancer cell (HuH-7) and human lung adenocarcinoma cell (A549).
Document (Journal of Organometallic Chemistry, 2016,864:It 48-58) reports, two hydrocarbon
Base tin acylhydrazone class Schiff base complex is to human lung adenocarcinoma cell (A549), human cervical carcinoma cell (HeLa), human breast cancer cell
(MCF-7) inhibiting effect of cancer cells such as.
It is the experiment proved that the substance with anticancer activity, present invention choosing based on acylhydrazone class Schiff organotin complex
It selects and tert-butyl benzoyl hydrazine, 2- batanone acid is reacted under certain condition with diphenyl stannous chloride, synthesis has been obtained to people's lung
Cancer cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) have the complex of certain inhibitory activity, are
Exploitation anticancer drug provides new approach.
Summary of the invention
There is provided a kind of ALPHA-ketobutyric acids to tert-butyl benzoyl hydrazone stannous phenide complex for the first object of the present invention.
The second object of the present invention is to provide above-mentioned ALPHA-ketobutyric acid to tert-butyl benzoyl hydrazone stannous phenide complex system
Preparation Method.
The third object of the present invention is to provide above-mentioned ALPHA-ketobutyric acid and exists to tert-butyl benzoyl hydrazone stannous phenide complex
Prepare the application in anticancer drug.
A kind of ALPHA-ketobutyric acid as the first aspect of the present invention is to tert-butyl benzoyl hydrazone stannous phenide complex
The complex of structure formula (I)
(I)
Wherein R is phenyl.
ALPHA-ketobutyric acid of the invention to tert-butyl benzoyl hydrazone stannous phenide complex through elemental analysis, infrared spectroscopy,
Nuclear magnetic resoance spectrum and X-ray single crystal diffraction structural analysis, it is as a result as follows：
Elemental analysis (C27H28N2O3Sn)：Calculated value：C 59.26, H 5.16, N 5.12；Measured value：C 59.30, H
5.20, N 5.10.
FT-IR (KBr, ν/cm-1): 3055, 2960, 2868, 1685, 1627, 1475, 1396, 1246,
1192, 1159, 1060, 833, 808, 729, 696, 594, 547, 495, 443, 420。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.28 (d, J =8.5 Hz, 2H), 7.81-7.83 (m,
4H), 7.54 (d, J =8.5 Hz, 2H), 7.45-7.49 (m, 6H), 3.49 (s, 3H), 3.08-3.13 (q,J =7.5 Hz, 2H), 1.38 (s, 9H), 1.30 (t, J =7.5 Hz, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.78, 163.47, 159.52, 156.69,
136.15, 135.71, 131.38, 129.39, 129.36, 128.62, 125.50, 35.17, 31.15, 21.16,
10.69。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.58。
ALPHA-ketobutyric acid of the invention is crystal structure, crystal three to tert-butyl benzoyl hydrazone stannous phenide complex
Oblique system, space group P-1, a=1.0242 (4) nm, b=1.1021 (4) nm, c=1.2065 (4) nm, α=
104.799 (4) °, β=102.901 (4) °, γ=92.927 (4) °, Z=2, V=1.2750 (8) nm3, Dc=1.425
Mg·m-3, m (MoK α)=1.031 mm-1, F (000)=556.
ALPHA-ketobutyric acid of the invention is structurally characterized in that tert-butyl benzoyl hydrazone stannous phenide complex：Tin in molecule
Atom is pentacoordinate distortion trigonal biyramid configuration.
ALPHA-ketobutyric acid of the invention has certain thermostabilization range to tert-butyl benzoyl hydrazone stannous phenide complex,
It can be stabilized at 233 DEG C or less.
A kind of ALPHA-ketobutyric acid as a second aspect of the invention is to tert-butyl benzoyl hydrazone stannous phenide complex
Diphenyl stannous chloride is added, to tert-butyl benzoyl hydrazine, 2- batanone acid in preparation method in the reaction vessel for having nitrogen protection
And solvent anhydrous methanol, 5 ~ 24 h are reacted under conditions of temperature is 45 ~ 65 DEG C, cooling, filtering, under conditions of 20 ~ 35 DEG C
Solvent volatilization crystallization is controlled, obtains yellow transparent crystal, as ALPHA-ketobutyric acid is to tert-butyl benzoyl hydrazone stannous phenide complex.
ALPHA-ketobutyric acid of the invention is to the preparation characteristic of tert-butyl benzoyl hydrazone stannous phenide complex：From letter relatively
The raw material being singly easy to get sets out, and without the separation of intermediate, directly obtains complicated molecule, i.e. one kettle way；Such reaction
Economically and environmentally on close friend advantageously.
In a preferred embodiment of the invention, the diphenyl stannous chloride, to tert-butyl benzoyl hydrazine, 2- butanone
The mass ratio of the material of sour three is 1:(1~1.05):(1.05~1.15).
In a preferred embodiment of the invention, the solvent anhydrous methanol dosage is every mM of diphenyl dichloride
Tin adds 15 ~ 35 milliliters.
A kind of ALPHA-ketobutyric acid as the third aspect of the present invention exists to tert-butyl benzoyl hydrazone stannous phenide complex
Prepare the application in anticancer drug.
It is living that applicant has carried out external anticancer to tert-butyl benzoyl hydrazone stannous phenide complex to above-mentioned ALPHA-ketobutyric acid
Property determine research, it is thus identified that ALPHA-ketobutyric acid has certain Anti-cancer biologic living tert-butyl benzoyl hydrazone stannous phenide complex
Property, that is to say, that the purposes of above-mentioned complex is to prepare the application in anticancer drug, is specifically exactly to prepare anti-human lung
Application in cancer, human liver cancer and human breast carcinoma drug.
ALPHA-ketobutyric acid of the invention is thin to human lung carcinoma cell, human liver cancer to tert-butyl benzoyl hydrazone stannous phenide complex
Born of the same parents and human breast cancer cell show good anticancer activity, and ALPHA-ketobutyric acid of the invention is to tert-butyl benzoyl hydrazone diphenyl
The features such as tin complex anticancer activity is high, at low cost, preparation method is simple, the anticancer drug to develop new provide new way.
Detailed description of the invention
Fig. 1 is IR spectrogram of the ALPHA-ketobutyric acid to tert-butyl benzoyl hydrazone stannous phenide complex.
Fig. 2 is ALPHA-ketobutyric acid to tert-butyl benzoyl hydrazone stannous phenide complex1H NMR spectra.
Fig. 3 is ALPHA-ketobutyric acid to tert-butyl benzoyl hydrazone stannous phenide complex13C NMR spectra.
Fig. 4 is ALPHA-ketobutyric acid to tert-butyl benzoyl hydrazone stannous phenide complex119Sn NMR spectra.
Fig. 5 is crystal structure figure of the ALPHA-ketobutyric acid to tert-butyl benzoyl hydrazone stannous phenide complex.
Fig. 6 is TG-DTG curve of the ALPHA-ketobutyric acid to tert-butyl benzoyl hydrazone stannous phenide complex.
Specific embodiment
By following specific embodiments, invention is further described in detail.
Embodiment 1：
Preparation of the ALPHA-ketobutyric acid to tert-butyl benzoyl hydrazone stannous phenide complex：
In the 100mL three-necked flask for having nitrogen protection be added 0.344g (1.0mmol) diphenyl stannous chloride,
0.192g (1.0mmol) to tert-butyl benzoyl hydrazine, 0.112g (1.1mmol) 2- batanone acid and 15mL solvent anhydrous methanol,
8 h are reacted under conditions of temperature is 45 ~ 65 DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains
Yellow transparent crystal, as ALPHA-ketobutyric acid are to tert-butyl benzoyl hydrazone stannous phenide complex.Yield：73.9%.Fusing point：233
~235℃(dec)。
Elemental analysis (C27H28N2O3Sn)：Calculated value：C 59.26, H 5.16, N 5.12；Measured value：C 59.30, H
5.20, N 5.10.
FT-IR (KBr, ν/cm-1): 3055, 2960, 2868, 1685, 1627, 1475, 1396, 1246,
1192, 1159, 1060, 833, 808, 729, 696, 594, 547, 495, 443, 420。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.28 (d, J =8.5 Hz, 2H), 7.81-7.83 (m,
4H), 7.54 (d, J =8.5 Hz, 2H), 7.45-7.49 (m, 6H), 3.49 (s, 3H), 3.08-3.13 (q,J =7.5 Hz, 2H), 1.38 (s, 9H), 1.30 (t, J =7.5 Hz, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.78, 163.47, 159.52, 156.69,
136.15, 135.71, 131.38, 129.39, 129.36, 128.62, 125.50, 35.17, 31.15, 21.16,
10.69。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.58。
Crystallographic data：Anorthic system, space group P-1, a=1.0242 (4) nm, b=1.1021 (4) nm, c=
1.2065 (4) nm, α=104.799 (4) °, β=102.901 (4) °, γ=92.927 (4) °, Z=2, V=1.2750 (8)
nm3, the Mgm of Dc=1.425-3, m (MoK α)=1.031 mm-1, F (000)=556.
Embodiment 2：
Preparation of the ALPHA-ketobutyric acid to tert-butyl benzoyl hydrazone stannous phenide complex：
In the 100mL three-necked flask for having nitrogen protection be added 0.344g (1.0mmol) diphenyl stannous chloride,
0.192g (1.0mmol) to tert-butyl benzoyl hydrazine, 0.107g (1.05mmol) 2- batanone acid and 35mL solvent anhydrous methanol,
5 h are reacted under conditions of temperature is 45 ~ 65 DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains
Yellow transparent crystal, as ALPHA-ketobutyric acid are to tert-butyl benzoyl hydrazone stannous phenide complex.Yield：76.5%.Fusing point：233
~235℃(dec)。
Elemental analysis (C27H28N2O3Sn)：Calculated value：C 59.26, H 5.16, N 5.12；Measured value：C 59.30, H
5.20, N 5.10.
FT-IR (KBr, ν/cm-1): 3055, 2960, 2868, 1685, 1627, 1475, 1396, 1246,
1192, 1159, 1060, 833, 808, 729, 696, 594, 547, 495, 443, 420。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.28 (d, J =8.5 Hz, 2H), 7.81-7.83 (m,
4H), 7.54 (d, J =8.5 Hz, 2H), 7.45-7.49 (m, 6H), 3.49 (s, 3H), 3.08-3.13 (q,J =7.5 Hz, 2H), 1.38 (s, 9H), 1.30 (t, J =7.5 Hz, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.78, 163.47, 159.52, 156.69,
136.15, 135.71, 131.38, 129.39, 129.36, 128.62, 125.50, 35.17, 31.15, 21.16,
10.69。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.58。
Crystallographic data：Anorthic system, space group P-1, a=1.0242 (4) nm, b=1.1021 (4) nm, c=
1.2065 (4) nm, α=104.799 (4) °, β=102.901 (4) °, γ=92.927 (4) °, Z=2, V=1.2750 (8)
nm3, the Mgm of Dc=1.425-3, m (MoK α)=1.031 mm-1, F (000)=556.
Embodiment 3：
Preparation of the ALPHA-ketobutyric acid to tert-butyl benzoyl hydrazone stannous phenide complex：
In the 100mL three-necked flask for having nitrogen protection be added 0.344g (1.0mmol) diphenyl stannous chloride,
0.202g (1.05mmol) is to tert-butyl benzoyl hydrazine, 0.117g (1.15mmol) 2- batanone acid and 25mL solvent without water beetle
Alcohol reacts 24 h under conditions of temperature is 45 ~ 65 DEG C, cooling, filtering, and solvent volatilization knot is controlled under conditions of 20 ~ 35 DEG C
Crystalline substance obtains yellow transparent crystal, and as ALPHA-ketobutyric acid is to tert-butyl benzoyl hydrazone stannous phenide complex.Yield：77.6%.It is molten
Point：233~235℃(dec).
Elemental analysis (C27H28N2O3Sn)：Calculated value：C 59.26, H 5.16, N 5.12；Measured value：C 59.30, H
5.20, N 5.10.
FT-IR (KBr, ν/cm-1): 3055, 2960, 2868, 1685, 1627, 1475, 1396, 1246,
1192, 1159, 1060, 833, 808, 729, 696, 594, 547, 495, 443, 420。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.28 (d, J =8.5 Hz, 2H), 7.81-7.83 (m,
4H), 7.54 (d, J =8.5 Hz, 2H), 7.45-7.49 (m, 6H), 3.49 (s, 3H), 3.08-3.13 (q,J =7.5 Hz, 2H), 1.38 (s, 9H), 1.30 (t, J =7.5 Hz, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.78, 163.47, 159.52, 156.69,
136.15, 135.71, 131.38, 129.39, 129.36, 128.62, 125.50, 35.17, 31.15, 21.16,
10.69。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.58。
Crystallographic data：Anorthic system, space group P-1, a=1.0242 (4) nm, b=1.1021 (4) nm, c=
1.2065 (4) nm, α=104.799 (4) °, β=102.901 (4) °, γ=92.927 (4) °, Z=2, V=1.2750 (8)
nm3, the Mgm of Dc=1.425-3, m (MoK α)=1.031 mm-1, F (000)=556.
Embodiment 4：
Preparation of the ALPHA-ketobutyric acid to tert-butyl benzoyl hydrazone stannous phenide complex：
In the 500mL three-necked flask for having nitrogen protection be added 3.440g (10.0mmol) diphenyl stannous chloride,
1.978g (10.3mmol) is to tert-butyl benzoyl hydrazine, 1.122g (11.0mmol) 2- batanone acid and 200mL solvent without water beetle
Alcohol reacts 22 h under conditions of temperature is 45 ~ 65 DEG C, cooling, filtering, and solvent volatilization knot is controlled under conditions of 20 ~ 35 DEG C
Crystalline substance obtains yellow transparent crystal, and as ALPHA-ketobutyric acid is to tert-butyl benzoyl hydrazone stannous phenide complex.Yield：71.7%.It is molten
Point：233~235℃(dec).
Elemental analysis (C27H28N2O3Sn)：Calculated value：C 59.26, H 5.16, N 5.12；Measured value：C 59.30, H
5.20, N 5.10.
FT-IR (KBr, ν/cm-1): 3055, 2960, 2868, 1685, 1627, 1475, 1396, 1246,
1192, 1159, 1060, 833, 808, 729, 696, 594, 547, 495, 443, 420。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.28 (d, J =8.5 Hz, 2H), 7.81-7.83 (m,
4H), 7.54 (d, J =8.5 Hz, 2H), 7.45-7.49 (m, 6H), 3.49 (s, 3H), 3.08-3.13 (q,J =7.5 Hz, 2H), 1.38 (s, 9H), 1.30 (t, J =7.5 Hz, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.78, 163.47, 159.52, 156.69,
136.15, 135.71, 131.38, 129.39, 129.36, 128.62, 125.50, 35.17, 31.15, 21.16,
10.69。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.58。
Crystallographic data：Anorthic system, space group P-1, a=1.0242 (4) nm, b=1.1021 (4) nm, c=
1.2065 (4) nm, α=104.799 (4) °, β=102.901 (4) °, γ=92.927 (4) °, Z=2, V=1.2750 (8)
nm3, the Mgm of Dc=1.425-3, m (MoK α)=1.031 mm-1, F (000)=556.
Test example：
To tert-butyl benzoyl hydrazone stannous phenide complex, Anticancer Activity in vitro, which measures, is ALPHA-ketobutyric acid of the invention
It is realized by MTT experiment method.
MTT analytic approach：
3- (4,5-Dimethylthiazol-2-yl) -2,5-diphenyltetrazolium 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.
The ALPHA-ketobutyric acid of the preparation of embodiment 1 is measured using mtt assay to tert-butyl benzoyl hydrazone stannous phenide complex
To the inhibitory activity of human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7).
Cell strain and cultivating system：H460, HepG2 and MCF7 cell strain are derived from American tissue incubator (ATCC).With containing
RPMI 1640 (GIBICO company) culture medium of 10% fetal calf serum, in 5% (volume fraction) CO2, 37 DEG C of saturated humidity incubators
Interior carry out in vitro culture.
Test process：Test medical fluid (1nM ~ 10 μM) is added separately in each hole according to the concentration gradient of concentration, often
A concentration sets 6 parallel holes.Experiment is divided into drug study group (the test medicine for being separately added into various concentration), control group (only plus is trained
Test medicine is not added in nutrient solution and cell) and blank group (only plus cultivating medicine, cell and test medicine is not added).Orifice plate after dosing is set
In 37 DEG C, 5%CO272h is cultivated in incubator.The activity of control drug is measured according to the method for test sample.Cultivating 72h
In orifice plate afterwards, every hole adds 40 μ L of MTT (being made into 4mg/mL with D-Hanks buffer).After 37 DEG C of placement 4h, upper layer is removed
Clear liquid.Every hole adds 150 μ L 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 7.0 program of Graph Pad Prism version, complex IC50Pass through journey
Nonlinear regression model (NLRM) in sequence with S-shaped dose response is fitted to obtain.
It is thin to human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) with MTT analytic approach
Born of the same parents' strain is analyzed, its IC is measured50Value, the results are shown in Table 1, and conclusion is：From the data in the table, with 2- carbonyl of the invention
Butyric acid is used as anticancer drug to tert-butyl benzoyl hydrazone stannous phenide complex, to human lung carcinoma cell (H460), human liver cancer cell
(HepG2) and human breast cancer cell (MCF7) has certain drug effect, can be used as the candidate compound of anticancer drug.
1 ALPHA-ketobutyric acid of table is to tert-butyl benzoyl hydrazone stannous phenide complex anticancer drug external activity test data.
| Human lung cancer | Human liver cancer | Human breast carcinoma | |
| Cell strain | H460 | HepG2 | MCF7 |
| IC50(μM) | 1.70±0.14 | 0.95±0.07 | 3.89±0.20 |
The ALPHA-ketobutyric acid of remaining embodiment preparation is to tert-butyl benzoyl hydrazone stannous phenide complex with mtt assay to people's lung
The same test example of anticancer activity test method of cancer cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7),
Test result and table 1 are essentially identical.
The above is only a preferred embodiment of the present invention and test example, is not intended to restrict the invention, it is clear that the skill of this field
Art personnel can carry out various changes, modification to the present invention without departing from the spirit and scope of the present invention.If to of the invention
These modifications and variations within the scope of the claims of the present invention and its equivalent technology, belong to protection model of the invention
It encloses.
Claims (6)
1. a kind of stannous phenide complex of ligand containing acylhydrazone is the complex of following structure formula (I)：
(I)
Wherein R is phenyl；The complex (I) is crystal structure, and crystallographic data is as follows：Anorthic system, space group P-
1, a=1.0242 (4) nm, b=1.1021 (4) nm, c=1.2065 (4) nm, α=104.799 (4) °, β=
102.901 (4) °, γ=92.927 (4) °, Z=2, V=1.2750 (8) nm3, the Mgm of Dc=1.425-3, m (MoK α)=
1.031 mm-1, F (000)=556；Tin atom is pentacoordinate distortion trigonal biyramid configuration in molecule；The complex (I)
Ir data：FT-IR (KBr, ν/cm-1): 3055, 2960, 2868, 1685, 1627, 1475, 1396,
1246, 1192, 1159, 1060, 833, 808, 729, 696, 594, 547, 495, 443, 420；Nuclear-magnetism composes number
According to：1H NMR (500 MHz, CDCl3, δ/ppm): 8.28 (d, J =8.5 Hz, 2H), 7.81-7.83 (m, 4H),
7.54 (d, J =8.5 Hz, 2H), 7.45-7.49 (m, 6H), 3.49 (s, 3H), 3.08-3.13 (q, J =
7.5 Hz, 2H), 1.38 (s, 9H), 1.30 (t, J=7.5 Hz, 3H)；13C NMR (126 MHz, CDCl3, δ/
ppm): 174.78, 163.47, 159.52, 156.69, 136.15, 135.71, 131.38, 129.39, 129.36,
128.62, 125.50, 35.17, 31.15, 21.16, 10.69；119Sn NMR (187 MHz, CDCl3, δ/ppm):
-294.58；The complex (I) can be stabilized at 233 DEG C or less.
2. the preparation method of the stannous phenide complex of the ligand described in claim 1 containing acylhydrazone, it is characterized in that there is nitrogen guarantor
Diphenyl stannous chloride is added in the reaction vessel of shield, to tert-butyl benzoyl hydrazine, 2- batanone acid and solvent anhydrous methanol, in temperature
Degree reacts 5 ~ 24 h under conditions of being 45 ~ 65 DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains
Yellow transparent crystal, as the stannous phenide complex of the ligand containing acylhydrazone.
3. preparation method as claimed in claim 2, which is characterized in that the diphenyl stannous chloride, to tert-butyl benzoyl
Hydrazine, 2- batanone acid three the mass ratio of the material be 1:(1~1.05):(1.05~1.15).
4. preparation method as claimed in claim 2, which is characterized in that the solvent anhydrous methanol dosage is every mM of hexichol
Base stannous chloride adds 15 ~ 35 milliliters.
5. the stannous phenide complex of the ligand containing acylhydrazone described in claim 1 is preparing the application in anticancer drug.
6. application described in claim 5, wherein the cancer cell is human lung carcinoma cell, human liver cancer cell, human breast cancer cell.
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