CN106336429A - 2-oxo-butyric acid p-methyl benzoyl hydrazone diphenyl tin complex and preparation method and application thereof - Google Patents

2-oxo-butyric acid p-methyl benzoyl hydrazone diphenyl tin complex and preparation method and application thereof Download PDF

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CN106336429A
CN106336429A CN201610735144.0A CN201610735144A CN106336429A CN 106336429 A CN106336429 A CN 106336429A CN 201610735144 A CN201610735144 A CN 201610735144A CN 106336429 A CN106336429 A CN 106336429A
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coordination compound
alpha
toluyl
stannous phenide
hydrazone stannous
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CN106336429B (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 2-oxo-butyric acid p-methyl benzoyl hydrazone diphenyl tin complex. The 2-oxo-butyric acid p-methyl benzoyl hydrazone diphenyl tin complex is a complex which has the following structural formula (I) (please see the formula in the description), wherein R represents a phenyl group. The invention further discloses a preparation method of the 2-oxo-butyric acid p-methyl benzoyl hydrazone diphenyl tin complex and application of the 2-oxo-butyric acid p-methyl benzoyl hydrazone diphenyl tin complex in preparation of anti-cancer drugs.

Description

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

Technical field

The present invention relates to a kind of ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide coordination compound and preparation method thereof, and This ALPHA-ketobutyric acid is preparing the application in cancer therapy drug to toluyl hydrazone stannous phenide coordination compound.

Background technology

Organotin is the metallo-organic compound that a class contains sn-c key.Researcher just noticed 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 mice and rat.But in 1972, brown found, By food or drug administration by injection, triphenyltin acetate ph3snoocch3The tumour growth of mice can be suppressed, and triphenyltin chloride Then can not.Between 1972 ~ 1977 years, the substantial amounts of organo-tin compound of Dutch scholar's research, but find no screening valency further The compound of value.They continue deeper into research, finally found that the tin compound of two organic group coordinations, such as tin-oxide (r2Sno), stannum hydroxide [ snr2(oh) x ] etc. have anti-tumor activity, and find out that they all contain or hydrolyze and can produce stannum oxygen Key.1986, crowe etc. was found that some organo-tin compounds have preferable active anticancer again, from this, resisted with regard to organotin The research of cancer activity becomes another extremely active focus after cisplatin.1989, American National anticancer research institute (national cancer institute) has carried out antitumor activity screening, result table to more than 2,000 kinds of organo-tin compounds Some organo-tin compounds bright have inhibitory action to p388 Lymphocytic leukemia.2002, gielen et al. was to organic The activity of stannum carboxylate compound has done comprehensive summing up, thinks that many organo-tin compounds have really preferably external after research Active anticancer.

Research shows, the organic group that organic tin atom connects and the part participating in being coordinated decide organo-tin compound Biological activity, select some to have the tin atom in organic ligand and the organotin of good biological activity in itself and be coordinated and cause The great interest of people.Acylhydrazone is by a class schiff alkali cpd of hydrazide kind compound modification, they Formed by aldehydes or ketones and hydrazides condensation, there is in molecule the of bonding similar with peptide bond, there is good biological activity, stronger joining Capability and various coordination mode, and have a wide range of applications at aspects such as medicine, pesticide, material and analytical reagents.Closely Nian Lai, both at home and abroad many research worker it is compared in terms of biological activity and in depth studies, research finds acylhydrazone class Compound has the various active such as anticancer, sterilization, antiinflammatory.Therefore, acylhydrazone class schiff aar ligand is combined with organotin it is intended to Obtain the higher noval chemical compound of biological activity, become people's research direction interested.

Chinese patent cn 102718794a discloses a kind of pair of acylhydrazone class schiff alkali stannous phenide coordination compound and its in system Application in standby Antilung gland cancer, colon cancer, the medicine of leukaemia.

Chinese patent cn 101851251a disclose a kind of dibutyl tin coordination compound of acylhydrazone class schiff aar ligand and its Application in preparation treatment hepatocarcinoma, adenocarcinoma of lung, breast carcinoma, carcinoma of prostate, colon cancer or early children's leukemic medicine of grain.

Document (journal of organometallic chemistry, 2014,75:83-91) is reported, organotin Acylhydrazone class schiff alkali coordination compound 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, 2013,724:23-31) is reported, series has Machine stannum acylhydrazone class schiff alkali coordination compound, organo-tin compound and acylhydrazone class schiff aar ligand are respectively to human lung adenocarcinoma cell (a549), the inhibitory action of the cancerous cell such as human colon cancer cell (hct-8), people in loop (hl-60).

Document (bioorganic & medicinal chemistry letters, 2015,25:4461- 4463) Report, the active anticancer to human liver cancer cell (huh-7) and human lung adenocarcinoma cell (a549) for multiple acylhydrazone class schiff aar ligands.

Document (journal of organometallic chemistry, 2016,864:48-58) is reported, two hydrocarbon Base stannum acylhydrazone class schiff alkali coordination compound is to human lung adenocarcinoma cell (a549), human cervical carcinoma cell (hela), human breast cancer cell (mcf-7) inhibitory action of cancerous cell such as.

It is to the experiment proved that the material with active anticancer based on acylhydrazone class schiff alkali organotin complex, the present invention selects Select and toluyl hydrazine, 2-butanone acid are reacted under certain condition with diphenyl stannum dichloride, synthesis has obtained to human lung cancer Cell (h460), human liver cancer cell (hepg2) and human breast cancer cell (mcf7) have the coordination compound of certain inhibitory activity, for opening Send out cancer therapy drug and provide new approach.

Content of the invention

The first object of the present invention there is provided a kind of ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide coordination compound.

The second object of the present invention is to provide above-mentioned ALPHA-ketobutyric acid prepared by toluyl hydrazone stannous phenide coordination compound Method.

The third object of the present invention is to provide above-mentioned ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide coordination compound in system Application in standby cancer therapy drug.

As a first aspect of the present invention a kind of ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide coordination compound, for knot The coordination compound of structure formula (i)

(i)

Wherein r is phenyl.

The ALPHA-ketobutyric acid of the present invention is to toluyl hydrazone stannous phenide coordination compound through elementary analysiss, infrared spectrum, core Magnetic resonance spectrum and x- ray single crystal diffraction structural analyses, result is as follows:

Elementary analysiss (c24h22n2o3Sn): value of calculation: 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 coordination compound, and its 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, dc=1.504 mg m-3, m (mok α)= 1.172 mm-1, f (000)=1016.

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

The ALPHA-ketobutyric acid of the present invention has certain thermally-stabilised scope to toluyl hydrazone stannous phenide coordination compound, Less than 196 DEG C can stable existence.

The system to toluyl hydrazone stannous phenide coordination compound for a kind of ALPHA-ketobutyric acid as a second aspect of the present invention Preparation Method, adds diphenyl stannum dichloride, sour and molten to toluyl hydrazine, 2-butanone in the reaction vessel having nitrogen protection Agent absolute methanol, reacts 5 ~ 24 h, cooling under conditions of temperature is 45 ~ 65 DEG C, filters, control under conditions of 20 ~ 35 DEG C Solvent volatilization crystallization, obtains yellow transparent crystal, as ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide coordination compound.

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

In a preferred embodiment of the invention, described diphenyl stannum dichloride, to toluyl hydrazine, 2-butanone acid The amount of the material of three is than for 1:(1 ~ 1.05): (1.05 ~ 1.15).

In a preferred embodiment of the invention, described solvent absolute methanol consumption is every mM of diphenyl dichloride Stannum adds 15 ~ and 35 milliliters.

A kind of ALPHA-ketobutyric acid as a third aspect of the present invention is being made to toluyl hydrazone stannous phenide coordination compound Application in standby cancer therapy drug.

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

The ALPHA-ketobutyric acid of the present invention is to toluyl hydrazone stannous phenide coordination compound to human lung carcinoma cell, human liver cancer cell Show good active anticancer with human breast cancer cell, the ALPHA-ketobutyric acid of the present invention is joined to toluyl hydrazone stannous phenide The features such as compound active anticancer height, low cost, preparation method are simple, the cancer therapy drug for developing new provides new way.

Brief description

Fig. 1 is the ir spectrogram to toluyl hydrazone stannous phenide coordination compound for the ALPHA-ketobutyric acid.

Fig. 2 is ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide coordination compound1H nmr spectrogram.

Fig. 3 is ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide coordination compound13C nmr spectrogram.

Fig. 4 is ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide coordination compound119Sn nmr spectrogram.

Fig. 5 is the crystal structure figure to toluyl hydrazone stannous phenide coordination compound for the ALPHA-ketobutyric acid.

Fig. 6 is the tg-dtg curve to toluyl hydrazone stannous phenide coordination compound for the ALPHA-ketobutyric acid.

Specific embodiment

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

Embodiment 1:

The preparation to toluyl hydrazone stannous phenide coordination compound for the ALPHA-ketobutyric acid:

0.344g (1.0mmol) diphenyl stannum dichloride, 0.150g is added in the 100ml there-necked flask having nitrogen protection (1.0mmol) to toluyl hydrazine, the acid of 0.112g (1.1mmol) 2-butanone and 15ml solvent absolute methanol, it is 45 in temperature 8 h are reacted under conditions of ~ 65 DEG C, cooling, filter, control solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtain yellow transparent brilliant Body, as ALPHA-ketobutyric acid are to toluyl hydrazone stannous phenide coordination compound.Yield: 80.9%.Fusing point: 196 ~ 198 DEG C (dec).

Elementary analysiss (c24h22n2o3Sn): value of calculation: 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:

The preparation to toluyl hydrazone stannous phenide coordination compound for the ALPHA-ketobutyric acid:

0.344g (1.0mmol) diphenyl stannum dichloride, 0.150g is added in the 100ml there-necked flask having nitrogen protection (1.0mmol) to toluyl hydrazine, the acid of 0.107g (1.05mmol) 2-butanone and 35ml solvent absolute methanol, in temperature it is 5 h are reacted under conditions of 45 ~ 65 DEG C, cooling, filter, control solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtain yellow transparent Crystal, as ALPHA-ketobutyric acid are to toluyl hydrazone stannous phenide coordination compound.Yield: 86.5%.Fusing point: 196 ~ 198 DEG C (dec).

Elementary analysiss (c24h22n2o3Sn): value of calculation: 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:

The preparation to toluyl hydrazone stannous phenide coordination compound for the ALPHA-ketobutyric acid:

0.344g (1.0mmol) diphenyl stannum dichloride, 0.157g is added in the 100ml there-necked flask having nitrogen protection (1.05mmol) to toluyl hydrazine, the acid of 0.117g (1.15mmol) 2-butanone and 25ml solvent absolute methanol, in temperature it is 24 h are reacted under conditions of 45 ~ 65 DEG C, cooling, filter, control solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtain yellow saturating Bright crystal, as ALPHA-ketobutyric acid are to toluyl hydrazone stannous phenide coordination compound.Yield: 84.6%.Fusing point: 196 ~ 198 DEG C (dec).

Elementary analysiss (c24h22n2o3Sn): value of calculation: 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:

The preparation to toluyl hydrazone stannous phenide coordination compound for the ALPHA-ketobutyric acid:

3.440g (10.0mmol) diphenyl stannum dichloride, 1.545g is added in the 500ml there-necked flask having nitrogen protection (10.3mmol) to toluyl hydrazine, the acid of 1.122g (11.0mmol) 2-butanone and 200ml solvent absolute methanol, in temperature For reacting 22 h under conditions of 45 ~ 65 DEG C, cooling, filter, control solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtain yellow Transparent crystal, as ALPHA-ketobutyric acid are to toluyl hydrazone stannous phenide coordination compound.Yield: 78.7%.Fusing point: 196 ~ 198 DEG C (dec).

Elementary analysiss (c24h22n2o3Sn): value of calculation: 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:

To toluyl hydrazone stannous phenide coordination compound, it is to pass through that its Anticancer Activity in vitro measures to the ALPHA-ketobutyric acid of the present invention Mtt experimental technique is realized.

Mtt analytic process:

With metabolism reduction 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide it is Basis.Succinate dehydrogenase in living cells mitochondria can make exogenous mtt be reduced to water-insoluble bluish violet crystallization first a ceremonial jade-ladle, used in libation (formazan) and be deposited in cell, and dead cell no this function.Dimethyl sulfoxide (dmso) can dissolve the first a ceremonial jade-ladle, used in libation in cell, Measure the optical density of characteristic wavelength with microplate reader, can indirectly reflect living cells quantity.

The ALPHA-ketobutyric acid of embodiment 1 preparation is measured to toluyl hydrazone stannous phenide coordination compound pair using mtt method 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 takes from American. tissue incubator (atcc).With containing Rpmi 1640 (gibico company) culture medium of 10% hyclone, in 5% (volume fraction) co2, 37 DEG C of saturated humidity incubators Inside carry out In vitro culture.

Test process: test medicinal liquid (1nm ~ 10 μm) is added separately in each hole according to the Concentraton gradient of concentration, often Individual concentration sets 6 parallel holes.Experiment is divided into drug study group (being separately added into the test medicine of variable concentrations), matched group (only to add training Nutrient solution and cell, are not added with testing medicine) and blank group (only adding culture medicine, be not added with cell and test medicine).Orifice plate after dosing is put In 37 DEG C, 5%co272h is cultivated in incubator.The activity of control drug measures according to the method for test sample.Cultivating 72h In orifice plate afterwards, every hole adds mtt 40 μ l (being made into 4mg/ml with d-hanks buffer).After placing 4h at 37 DEG C, remove upper strata Clear liquid.Every hole adds 150 μ l dmso, vibrates 5min, makes formazan crystallize dissolving.Finally, using automatic microplate reader in 570nm The optical density in each hole is detected at wavelength.

Data processing: data processing uses graph pad prism version 7.0 program, coordination compound ic50By journey The nonlinear regression model (NLRM) in sequence with s shape dose response is fitted obtaining.

Thin to human lung carcinoma cell (h460), human liver cancer cell (hepg2) and human breast cancer cell (mcf7) with mtt analytic process Born of the same parents' strain is analyzed, and measures its ic50Value, as shown in table 1, conclusion is result: from data in table, with the 2- carbonyl of the present invention Butanoic acid is used as cancer therapy drug to toluyl hydrazone stannous phenide coordination compound, 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 cancer therapy drug.

Table 1 ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide coordination compound cancer therapy 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

Remaining embodiment preparation ALPHA-ketobutyric acid to toluyl hydrazone stannous phenide coordination compound with mtt method to human lung cancer The same test example of active anticancer method of testing of cell (h460), human liver cancer cell (hepg2) and human breast cancer cell (mcf7), surveys Test result is essentially identical with table 1.

These are only the preferred embodiments of the present invention and test example, be not limited to the present invention it is clear that the skill of this area Art personnel can carry out various changes, modification without departing from the spirit and scope of the present invention to the present invention.If to the present invention's These modifications and modification belong within the scope of the claims in the present invention and its equivalent technologies, belong to the protection model of the present invention Enclose.

Claims (9)

1. a kind of ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide coordination compound, for the coordination compound of following structural formula (i):
(i)
Wherein r is phenyl.
2. contain a kind of ALPHA-ketobutyric acid as claimed in claim 1 to toluyl hydrazone stannous phenide coordination compound, it is infrared Spectroscopic data: 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;Its nuclear-magnetism modal data: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.
3. ALPHA-ketobutyric acid as claimed in claim 1 is to toluyl hydrazone stannous phenide coordination compound, wherein, described 2- Carbonyl butanoic acid is crystal structure to toluyl hydrazone stannous phenide coordination compound, and its 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, dc=1.504 mg m-3, m (mok α)=1.172 mm-1, f (000) = 1016;In molecule, tin atom is hexa-coordinate distorted octahedron configuration.
4. ALPHA-ketobutyric acid described in claim 1 has certain thermally-stabilised model to toluyl hydrazone stannous phenide coordination compound Enclose, can stable existence below 196 DEG C.
5. the preparation method to toluyl hydrazone stannous phenide coordination compound for the ALPHA-ketobutyric acid described in claim 1, its feature Be have nitrogen protection reaction vessel in add diphenyl stannum dichloride, to toluyl hydrazine, 2-butanone acid and solvent no Water methanol, reacts 5 ~ 24 h, cooling under conditions of temperature is 45 ~ 65 DEG C, filters, and 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 coordination compound.
6. preparation as claimed in claim 5 method it is characterised in that described diphenyl stannum dichloride, to toluyl Hydrazine, the amount ratio of the material of 2-butanone acid three are for 1:(1 ~ 1.05): (1.05 ~ 1.15).
7. the method for preparation as claimed in claim 5 is it is characterised in that described solvent absolute methanol consumption is every mM two Phenyl dichloro stannum adds 15 ~ and 35 milliliters.
8. ALPHA-ketobutyric acid described in claim 1 is preparing answering in cancer therapy drug to toluyl hydrazone stannous phenide coordination compound With.
9. the application described in claim 8, wherein said cancerous cell is human lung carcinoma cell, human liver cancer cell, human breast cancer cell.
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CN105237562A (en) * 2015-11-11 2016-01-13 衡阳师范学院 2-oxo propionic acid salicyloyl hydrazone tin diphenyl complex and preparation method and application thereof
CN105237563A (en) * 2015-11-11 2016-01-13 衡阳师范学院 2-oxo propionic acid p-hydroxy benzoyl hydrazone bis(2,4-dichlorobenzyl) tin complex and preparation method and application thereof
CN105348318A (en) * 2015-11-11 2016-02-24 衡阳师范学院 2-carbonyl butyric acid benzoyl hydrazone dibenzyl tin complex, preparation method therefor and applications

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Publication number Priority date Publication date Assignee Title
CN105237562A (en) * 2015-11-11 2016-01-13 衡阳师范学院 2-oxo propionic acid salicyloyl hydrazone tin diphenyl complex and preparation method and application thereof
CN105237563A (en) * 2015-11-11 2016-01-13 衡阳师范学院 2-oxo propionic acid p-hydroxy benzoyl hydrazone bis(2,4-dichlorobenzyl) tin complex and preparation method and application thereof
CN105348318A (en) * 2015-11-11 2016-02-24 衡阳师范学院 2-carbonyl butyric acid benzoyl hydrazone dibenzyl tin complex, preparation method therefor and applications

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