CN106336429B - A kind of ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex and its preparation method and application - Google Patents

A kind of ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex and its preparation method and application Download PDF

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CN106336429B
CN106336429B CN201610735144.0A CN201610735144A CN106336429B CN 106336429 B CN106336429 B CN 106336429B CN 201610735144 A CN201610735144 A CN 201610735144A CN 106336429 B CN106336429 B CN 106336429B
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complex
alpha
ketobutyric acid
toluyl
stannous phenide
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CN106336429A (en
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蒋伍玖
谭宇星
张复兴
朱小明
邝代治
冯泳兰
庾江喜
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衡阳师范学院
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00Compounds containing elements of Groups 4 or 14 of the Periodic System
    • C07F7/22Tin compounds
    • C07F7/2284Compounds with one or more Sn-N linkages
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13Crystalline forms, e.g. polymorphs

Abstract

The invention discloses a kind of 2 carbonyl butyric acid to toluyl hydrazone stannous phenide complex, is the complex of following structure formula (I), wherein R is phenyl.The invention also discloses preparation method of the 2 carbonyl butyric acid to toluyl hydrazone stannous phenide complex and the applications in preparing anticancer drug.

Description

A kind of ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex and its preparation side Method and application

Technical field

The present invention relates to a kind of ALPHA-ketobutyric acids to toluyl hydrazone stannous phenide complex and preparation method thereof, and Application of the ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex in preparing anticancer drug.

Background technology

Organotin is a kind of metallo-organic compound containing Sn-C keys.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 trace back 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 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 antitumor activity, and find out that they all contain or hydrolyze and can generate tin oxygen Key.1986, Crowe etc. was found that some organo-tin compounds have preferable active anticancer 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 Some bright organo-tin compounds have inhibiting effect to P388 lymphocytic leukemias.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 Active anticancer.

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 some itself have the active organic ligand of good biological in organotin tin atom be coordinated cause The great interest of people.Acylhydrazone is a kind of Schiff compound made of being modified by 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 various coordination mode, and have a wide range of applications in medicine, pesticide, material and analytical reagent etc..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, acylhydrazone class Schiff ligand is combined 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 disclose a kind of double acylhydrazone class Schiff stannous phenide complexs and its are 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 for preparing 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, active anticancer 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 active anticancer, present invention choosing based on acylhydrazone class Schiff organotin complex It selects and toluyl hydrazine, 2- batanone acids is reacted under certain condition with diphenyl stannous chloride, synthesis has been obtained to human lung cancer Cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) have the complex of certain inhibitory activity, to open Hair anticancer drug provides new approach.

Invention content

There is provided a kind of ALPHA-ketobutyric acids to toluyl 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 and is prepared to toluyl hydrazone stannous phenide complex Method.

The third object of the present invention is to provide above-mentioned ALPHA-ketobutyric acid and is being made to toluyl hydrazone stannous phenide complex Application in standby anticancer drug.

A kind of ALPHA-ketobutyric acid as the first aspect of the present invention is to toluyl hydrazone stannous phenide complex, for knot The complex of structure formula (I)

(I)

Wherein R is phenyl.

The ALPHA-ketobutyric acid of the present invention is to toluyl hydrazone stannous phenide complex through elemental analysis, infrared spectrum, core Magnetic resonance spectrum and X-ray single crystal diffraction structural analysis, it is as a result as follows:

Elemental analysis (C24H22N2O3Sn):Calculated value:C 57.06, H 4.39, N 5.55;Measured value:C 57.10, H 4.41, N 5.55.

FT-IR (KBr, ν/cm-1): 3059, 3043, 2980, 2937, 2879, 1633, 1597, 1581, 1490, 1479, 1394, 1340, 1062, 844, 750, 732, 694, 626, 605, 586, 543, 487, 451。

1H NMR (500 MHz, CDCl3, δ/ppm): 8.23 (d, J =8.2 Hz, 2H), 7.81-7.83 (m, 4H), 7.45-7.48 (m, 6H), 7.32 (d, J =7.9 Hz, 2H), 3.49 (s, 3H), 3.08-3.13 (q,J =7.5 Hz, 2H), 2.46 (s, 3H), 1.30 (t, J =7.5 Hz, 3H)。

13C NMR (126 MHz, CDCl3, δ/ppm): 174.84, 163.45, 159.51, 143.66, 136.14, 135.73, 131.38, 129.44, 129.37, 129.24, 128.78, 21.81, 21.15, 10.71。

119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.70。

The ALPHA-ketobutyric acid of the present invention is crystal structure to toluyl hydrazone stannous phenide complex, and crystal is monocline Crystallographic system, space group P2 (1)/n, a=1.3093 (3) nm, b=0.89534 (17) nm, c=1.9338 (4) nm, α= γ=90 °, β=100.208 (3) °, Z=4, V=2.2310 (7) nm3, the Mgm of Dc=1.504-3, m (MoK α)= 1.172 mm-1, F (000)=1016.

The ALPHA-ketobutyric acid of the present invention is structurally characterized in that toluyl hydrazone stannous phenide complex:Tin is former in molecule Son is hexa-coordinate distorted octahedron configuration.

The ALPHA-ketobutyric acid of the present invention has certain thermostabilization range to toluyl hydrazone stannous phenide complex, 196 DEG C or less can be stabilized.

A kind of ALPHA-ketobutyric acid as the second aspect of the present invention is to the system of toluyl hydrazone stannous phenide complex Diphenyl stannous chloride is added, to toluyl hydrazine, 2- batanone acids and molten in Preparation Method in the reaction vessel for having nitrogen protection Agent absolute methanol reacts 5 ~ 24 h under conditions of temperature is 45 ~ 65 DEG C, cooling, and filtering controls under conditions of 20 ~ 35 DEG C Solvent volatilization crystallization, obtains yellow transparent crystal, as ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex.

The present invention ALPHA-ketobutyric acid be to the preparation characteristic of toluyl hydrazone stannous phenide complex:From relatively easy The raw material being easy to get sets out, and without the separation of intermediate, directly obtains complicated molecule, i.e. one kettle way;Such reaction exists Economically with it is environmental-friendly on advantageously.

In a preferred embodiment of the invention, the diphenyl stannous chloride, to toluyl hydrazine, 2- batanone acids The amount ratio of the substance of three is 1:(1~1.05):(1.05~1.15).

In a preferred embodiment of the invention, the solvent absolute 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 is making toluyl hydrazone stannous phenide complex Application in standby anticancer drug.

Applicant has carried out Anticancer Activity in vitro to above-mentioned ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex Determining research, it is thus identified that ALPHA-ketobutyric acid has certain anticancer bioactive to toluyl hydrazone stannous phenide complex, That is the purposes of above-mentioned complex is the application in preparing anticancer drug, be exactly specifically prepare anti-human lung cancer, Application in human liver cancer and human breast carcinoma drug.

The ALPHA-ketobutyric acid of the present invention is to toluyl hydrazone stannous phenide complex to human lung carcinoma cell, human liver cancer cell Show that good active anticancer, ALPHA-ketobutyric acid of the invention match toluyl hydrazone stannous phenide with human breast cancer cell The features such as object active anticancer is high, at low cost, preparation method is simple is closed, the anticancer drug to develop new provides new way.

Description of the drawings

Fig. 1 is IR spectrogram of the ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex.

Fig. 2 is ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex1H NMR spectras.

Fig. 3 is ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex13C NMR spectras.

Fig. 4 is ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex119Sn NMR spectras.

Fig. 5 is crystal structure figure of the ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex.

Fig. 6 is TG-DTG curve of the ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex.

Specific implementation mode

By detailed description below, invention is further described in detail.

Embodiment 1:

Preparation of the ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex:

Be added in the 100mL three-necked flasks for having nitrogen protection 0.344g (1.0mmol) diphenyl stannous chloride, 0.150g (1.0mmol) to toluyl hydrazine, 0.112g (1.1mmol) 2- batanone acids and 15mL solvent absolute methanols, Temperature reacts 8 h under conditions of being 45 ~ 65 DEG C, cooling, filtering, and solvent volatilization crystallization is controlled under conditions of 20 ~ 35 DEG C, is obtained yellow Color transparent crystal, as ALPHA-ketobutyric acid are to toluyl hydrazone stannous phenide complex.Yield:80.9%.Fusing point:196~198 ℃(dec)。

Elemental analysis (C24H22N2O3Sn):Calculated value:C 57.06, H 4.39, N 5.55;Measured value:C 57.10, H 4.41, N 5.55.

FT-IR (KBr, ν/cm-1): 3059, 3043, 2980, 2937, 2879, 1633, 1597, 1581, 1490, 1479, 1394, 1340, 1062, 844, 750, 732, 694, 626, 605, 586, 543, 487, 451。

1H NMR (500 MHz, CDCl3, δ/ppm): 8.23 (d, J =8.2 Hz, 2H), 7.81-7.83 (m, 4H), 7.45-7.48 (m, 6H), 7.32 (d, J =7.9 Hz, 2H), 3.49 (s, 3H), 3.08-3.13 (q,J =7.5 Hz, 2H), 2.46 (s, 3H), 1.30 (t, J =7.5 Hz, 3H)。

13C NMR (126 MHz, CDCl3, δ/ppm): 174.84, 163.45, 159.51, 143.66, 136.14, 135.73, 131.38, 129.44, 129.37, 129.24, 128.78, 21.81, 21.15, 10.71。

119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.70。

Crystallographic data:Monoclinic system, space group P2 (1)/n, a=1.3093 (3) nm, b=0.89534 (17) Nm, c=1.9338 (4) nm, α=γ=90 °, β=100.208 (3) °, Z=4, V=2.2310 (7) nm3, Dc= 1.504 Mg·m-3, m (MoK α)=1.172 mm-1, F (000)=1016.

Embodiment 2:

Preparation of the ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex:

Be added in the 100mL three-necked flasks for having nitrogen protection 0.344g (1.0mmol) diphenyl stannous chloride, 0.150g (1.0mmol) to toluyl hydrazine, 0.107g (1.05mmol) 2- batanone acids and 35mL solvent absolute methanols, Temperature reacts 5 h under conditions of being 45 ~ 65 DEG C, cooling, filtering, and solvent volatilization crystallization is controlled under conditions of 20 ~ 35 DEG C, is obtained yellow Color transparent crystal, as ALPHA-ketobutyric acid are to toluyl hydrazone stannous phenide complex.Yield:86.5%.Fusing point:196~198 ℃(dec)。

Elemental analysis (C24H22N2O3Sn):Calculated value:C 57.06, H 4.39, N 5.55;Measured value:C 57.10, H 4.41, N 5.55.

FT-IR (KBr, ν/cm-1): 3059, 3043, 2980, 2937, 2879, 1633, 1597, 1581, 1490, 1479, 1394, 1340, 1062, 844, 750, 732, 694, 626, 605, 586, 543, 487, 451。

1H NMR (500 MHz, CDCl3, δ/ppm): 8.23 (d, J =8.2 Hz, 2H), 7.81-7.83 (m, 4H), 7.45-7.48 (m, 6H), 7.32 (d, J =7.9 Hz, 2H), 3.49 (s, 3H), 3.08-3.13 (q,J =7.5 Hz, 2H), 2.46 (s, 3H), 1.30 (t, J =7.5 Hz, 3H)。

13C NMR (126 MHz, CDCl3, δ/ppm): 174.84, 163.45, 159.51, 143.66, 136.14, 135.73, 131.38, 129.44, 129.37, 129.24, 128.78, 21.81, 21.15, 10.71。

119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.70。

Crystallographic data:Monoclinic system, space group P2 (1)/n, a=1.3093 (3) nm, b=0.89534 (17) Nm, c=1.9338 (4) nm, α=γ=90 °, β=100.208 (3) °, Z=4, V=2.2310 (7) nm3, Dc= 1.504 Mg·m-3, m (MoK α)=1.172 mm-1, F (000)=1016.

Embodiment 3:

Preparation of the ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex:

Be added in the 100mL three-necked flasks for having nitrogen protection 0.344g (1.0mmol) diphenyl stannous chloride, 0.157g (1.05mmol) to toluyl hydrazine, 0.117g (1.15mmol) 2- batanone acids and 25mL solvent absolute methanols, 24 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, Yellow transparent crystal is obtained, as ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex.Yield:84.6%.Fusing point:196 ~198℃(dec)。

Elemental analysis (C24H22N2O3Sn):Calculated value:C 57.06, H 4.39, N 5.55;Measured value:C 57.10, H 4.41, N 5.55.

FT-IR (KBr, ν/cm-1): 3059, 3043, 2980, 2937, 2879, 1633, 1597, 1581, 1490, 1479, 1394, 1340, 1062, 844, 750, 732, 694, 626, 605, 586, 543, 487, 451。

1H NMR (500 MHz, CDCl3, δ/ppm): 8.23 (d, J =8.2 Hz, 2H), 7.81-7.83 (m, 4H), 7.45-7.48 (m, 6H), 7.32 (d, J =7.9 Hz, 2H), 3.49 (s, 3H), 3.08-3.13 (q,J =7.5 Hz, 2H), 2.46 (s, 3H), 1.30 (t, J =7.5 Hz, 3H)。

13C NMR (126 MHz, CDCl3, δ/ppm): 174.84, 163.45, 159.51, 143.66, 136.14, 135.73, 131.38, 129.44, 129.37, 129.24, 128.78, 21.81, 21.15, 10.71。

119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.70。

Crystallographic data:Monoclinic system, space group P2 (1)/n, a=1.3093 (3) nm, b=0.89534 (17) Nm, c=1.9338 (4) nm, α=γ=90 °, β=100.208 (3) °, Z=4, V=2.2310 (7) nm3, Dc= 1.504 Mg·m-3, m (MoK α)=1.172 mm-1, F (000)=1016.

Embodiment 4:

Preparation of the ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide complex:

Be added in the 500mL three-necked flasks for having nitrogen protection 3.440g (10.0mmol) diphenyl stannous chloride, 1.545g (10.3mmol) to toluyl hydrazine, 1.122g (11.0mmol) 2- batanone acids and 200mL solvent absolute methanols, 22 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, Yellow transparent crystal is obtained, as ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex.Yield:78.7%.Fusing point:196 ~198℃(dec)。

Elemental analysis (C24H22N2O3Sn):Calculated value:C 57.06, H 4.39, N 5.55;Measured value:C 57.10, H 4.41, N 5.55.

FT-IR (KBr, ν/cm-1): 3059, 3043, 2980, 2937, 2879, 1633, 1597, 1581, 1490, 1479, 1394, 1340, 1062, 844, 750, 732, 694, 626, 605, 586, 543, 487, 451。

1H NMR (500 MHz, CDCl3, δ/ppm): 8.23 (d, J =8.2 Hz, 2H), 7.81-7.83 (m, 4H), 7.45-7.48 (m, 6H), 7.32 (d, J =7.9 Hz, 2H), 3.49 (s, 3H), 3.08-3.13 (q,J =7.5 Hz, 2H), 2.46 (s, 3H), 1.30 (t, J =7.5 Hz, 3H)。

13C NMR (126 MHz, CDCl3, δ/ppm): 174.84, 163.45, 159.51, 143.66, 136.14, 135.73, 131.38, 129.44, 129.37, 129.24, 128.78, 21.81, 21.15, 10.71。

119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.70。

Crystallographic data:Monoclinic system, space group P2 (1)/n, a=1.3093 (3) nm, b=0.89534 (17) Nm, c=1.9338 (4) nm, α=γ=90 °, β=100.208 (3) °, Z=4, V=2.2310 (7) nm3, Dc= 1.504 Mg·m-3, m (MoK α)=1.172 mm-1, F (000)=1016.

Test example:

For the ALPHA-ketobutyric acid of the present invention to toluyl hydrazone stannous phenide complex, Anticancer Activity in vitro measurement is logical Cross the realization of 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) (DMSO) can dissolve cell In first a ceremonial jade-ladle, used in libation, with microplate reader measure characteristic wavelength optical density, can reflect living cells quantity indirectly.

The ALPHA-ketobutyric acid of the preparation of embodiment 1 is measured to toluyl hydrazone stannous phenide complex pair using mtt assay 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 companies) 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 liquid (1nM ~ 10 μM) is added separately to according to the concentration gradient of concentration in each hole, 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 Nutrient solution and cell are not added with test medicine) and blank group (only plus cultivating medicine, be not added with cell and test medicine).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, add 40 μ L of MTT (being made into 4mg/mL with D-Hanks buffer solutions) per hole.After placing 4h at 37 DEG C, upper layer is removed Clear liquid.Add 150 μ L DMSO per hole, vibrate 5min, makes Formazan crystallization dissolvings.Finally, using automatic microplate reader in 570nm The optical density in each hole is detected at wavelength.

Data processing:Data processing uses 7.0 programs of Graph Pad Prism version, complex IC50Pass through journey The nonlinear regression model (NLRM) with S-shaped dose response is fitted to obtain in sequence.

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 the 2- carbonyls of the present invention Butyric acid is used as anticancer drug to toluyl 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 toluyl 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) 1.65±0.27 1.81±0.21 1.20±0.12

ALPHA-ketobutyric acid prepared by remaining embodiment is to toluyl hydrazone stannous phenide complex with mtt assay to human lung cancer The same test example of active anticancer test method of cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) is surveyed Test result and table 1 are essentially identical.

It these are only the preferred embodiment of the present invention and test example, be not intended to restrict the invention, it is clear that the skill of this field Art personnel can carry out the present invention various changes, modification without departing from the spirit and scope of the present invention.If to the present invention's These modifications and variations within the scope of the claims of the present invention and its equivalent technology, belong to the protection model of the present invention It encloses.

Claims (6)

  1. It is the complex of following structure formula (I) 1. a kind of ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex:
    (I)
    Wherein R is phenyl;The complex (I) is crystal structure, and crystallographic data is as follows:Monoclinic system, space group P2 (1)/n, a=1.3093 (3) nm, b=0.89534 (17) nm, c=1.9338 (4) nm, α=γ=90 °, β= 100.208 (3) °, Z=4, V=2.2310 (7) nm3, the Mgm of Dc=1.504-3, m (MoK α)=1.172 mm-1, F (000) = 1016;Tin atom is hexa-coordinate distorted octahedron configuration in molecule;The ir data of the complex (I):FT-IR (KBr, ν/cm-1): 3059, 3043, 2980, 2937, 2879, 1633, 1597, 1581, 1490, 1479, 1394, 1340, 1062, 844, 750, 732, 694, 626, 605, 586, 543, 487, 451;Nuclear-magnetism composes number According to:1H NMR (500 MHz, CDCl3, δ/ppm): 8.23 (d, J =8.2 Hz, 2H), 7.81-7.83 (m, 4H), 7.45-7.48 (m, 6H), 7.32 (d, J =7.9 Hz, 2H), 3.49 (s, 3H), 3.08-3.13 (q, J = 7.5 Hz, 2H), 2.46 (s, 3H), 1.30 (t, J =7.5 Hz, 3H);13C NMR (126 MHz, CDCl3, δ/ ppm): 174.84, 163.45, 159.51, 143.66, 136.14, 135.73, 131.38, 129.44, 129.37, 129.24, 128.78, 21.81, 21.15, 10.71;119Sn NMR (187 MHz, CDCl3, δ/ppm): - 294.70;The complex (I) can be stabilized at 196 DEG C or less.
  2. 2. ALPHA-ketobutyric acid described in claim 1 is to the preparation method of toluyl hydrazone stannous phenide complex, feature Be be added in the reaction vessel for having nitrogen protection diphenyl stannous chloride, to toluyl hydrazine, 2- batanone acids and solvent without Water methanol reacts 5 ~ 24 h under conditions of temperature is 45 ~ 65 DEG C, cooling, and filtering controls solvent under conditions of 20 ~ 35 DEG C Volatilization crystallization, obtains yellow transparent crystal, as ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex.
  3. 3. preparation method as claimed in claim 2, which is characterized in that the diphenyl stannous chloride, to toluyl hydrazine, The amount ratio of the substance of 2- batanone acid threes is 1:(1~1.05):(1.05~1.15).
  4. 4. preparation method as claimed in claim 2, which is characterized in that the solvent absolute methanol dosage is every mM of hexichol Base stannous chloride adds 15 ~ 35 milliliters.
  5. 5. ALPHA-ketobutyric acid described in claim 1 is to toluyl hydrazone stannous phenide complex answering in preparing anticancer drug With.
  6. 6. the 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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