CN106279260A - A kind of 2 carbonyl butanoic acid salicyloyl hydrazone di-n-butyl tin coordination compounds and its preparation method and application - Google Patents

A kind of 2 carbonyl butanoic acid salicyloyl hydrazone di-n-butyl tin coordination compounds and its preparation method and application Download PDF

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CN106279260A
CN106279260A CN201610691922.0A CN201610691922A CN106279260A CN 106279260 A CN106279260 A CN 106279260A CN 201610691922 A CN201610691922 A CN 201610691922A CN 106279260 A CN106279260 A CN 106279260A
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coordination compound
butyl tin
alpha
salicyloyl hydrazone
di
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CN106279260B (en
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谭宇星
蒋伍玖
庾江喜
张复兴
朱小明
邝代治
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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

Abstract

The invention discloses a kind of 2 carbonyl butanoic acid salicyloyl hydrazone di-n-butyl tin coordination compounds, for the coordination compound of following structure formula (I), wherein R is normal-butyl.The invention also discloses the preparation method of this 2 carbonyl butanoic acid salicyloyl hydrazone di-n-butyl tin coordination compound and the application in preparing cancer therapy drug.

Description

A kind of ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound and preparation method thereof and Application

Technical field

The present invention relates to a kind of ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound and preparation method thereof, and this 2- The application in preparing cancer therapy drug of the carbonyl butanoic acid salicyloyl hydrazone di-n-butyl tin 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 Ph3SnOOCCH3Can suppress the tumor growth of mice, and triphenyltin chloride Then can not.Between 1972 ~ 1977 years, Holland's substantial amounts of organo-tin compound of scholar's research, but find no further screening valency 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 an anti-tumor activity, and find out that they all contain or hydrolyze and can produce stannum oxygen Key.1980, Crowe etc. was found that again some organo-tin compounds have preferable active anticancer, from this, resisted about 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 Brighter organo-tin compounds 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 the most external really after research Active anticancer.

Research shows, the organic group that organotin atom connects and the part participating in coordination decide organo-tin compound Biological activity, select some itself have good biological activity organic ligand with in organotin tin atom coordination cause The great interest of people.Acylhydrazone is by a class Schiff compound of hydrazide kind compound modification, they It is condensed by aldehydes or ketones and hydrazides and forms, molecule has 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, it is compared in terms of biological activity by the most many research worker in depth studies, and research finds acylhydrazone class Compound has the various active such as anticancer, sterilization, antiinflammatory.Therefore, acylhydrazone class Schiff part is combined with organotin, it is intended to Obtain the noval chemical compound that biological activity is higher, become the research direction that people are interested.

Chinese patent CN 102718794A discloses a kind of double acylhydrazone class Schiff stannous phenide coordination compound and in system Standby Antilung gland cancer, colon cancer, leukaemia medicine in application.

Chinese patent CN 101851251A disclose a kind of acylhydrazone class Schiff part dibutyl tin coordination compound and Application in preparation treatment hepatocarcinoma, adenocarcinoma of lung, breast carcinoma, carcinoma of prostate, colon cancer or the youngest leukemic medicine of grain.

Document (Journal of Organometallic Chemistry, 2014,75:83-91) is reported, 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 relatively 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 base complex, organo-tin compound and acylhydrazone class Schiff part 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, multiple acylhydrazone class Schiff part is to human liver cancer cell (HuH-7) and the active anticancer of human lung adenocarcinoma cell (A549).

Document (Journal of Organometallic Chemistry, 2016,804:48-58) is reported, two hydrocarbon Base stannum acylhydrazone class Schiff base complex 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.

Being the material that the experiment proved that and have active anticancer based on acylhydrazone class Schiff organotin complex, the present invention selects Select salicylyl hydrazine, 2-butanone acid is reacted under certain condition with di-nbutyltin oxide, and synthesis has obtained human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) there is the coordination compound of certain inhibitory activity, anti-for exploitation Cancer drug provides new approach.

Summary of the invention

The first object of the present invention there is provided a kind of ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound.

The second object of the present invention is to provide above-mentioned ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound preparation method.

It is anti-in preparation that the third object of the present invention is to provide above-mentioned ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound Application in cancer drug.

As a kind of ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound of a first aspect of the present invention, for structural formula (I) coordination compound

(I)

Wherein R is normal-butyl.

The ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound of the present invention is common through elementary analysis, infrared spectrum, nuclear-magnetism Shaking and compose and X-ray single crystal diffraction structural analysis, result is as follows:

Elementary analysis (C19H28N2O4Sn): value of calculation: C 48.85, H 6.04, N 6.00;Measured value: C 48.90, H 6.00, N 6.02。

FT-IR (KBr, ν/cm-1): 3053, 3018, 2956, 2924, 2872, 1614, 1598, 1519, 1489, 1456, 1330, 1255, 1205, 1168, 1087, 831, 754, 673, 603, 534, 516, 443。

1H NMR (500 MHz, CDCl3, δ/ppm): 11.94 (s, 1H), 8.07~8.09 (m, 1H), 7.45 ~7.48 (m, 1H), 7.02 (d, J =8.2 Hz, 1H), 6.95~7.03 (t, J =7.5 Hz, 1H), 3.01~ 3.05 (q, J =7.6 Hz, 2H), 1.63~1.66 (m, 4H), 1.46~1.48 (m, 4H), 1.27~1.31 (m, 7H), 0.84 (t, J =7.6 Hz, 6H)。

13C NMR (126 MHz, CDCl3, δ/ppm): 175.75, 165.72, 160.71, 157.59, 134.85, 130.29, 119.21, 117.52, 115.32, 26.81, 26.30, 25.04, 21.19, 13.47, 9.88。

The ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound of the present invention is crystal structure, and its crystal is monoclinic crystal System, space group C2/c, a=2.37834 (9) nm, b=0.87817 (3) nm, c=2.34607 (9) nm, α=γ= 90 °, β=118.4680 (10) °, Z=8, V=4.3075 (3) nm3, Dc=1.441 Mg m-3, m (MoK α)=1.210 mm-1, F (000)=1904.

Being structurally characterized in that of the ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound of the present invention: in molecule, tin atom is Hexa-coordinate distorted octahedron configuration.

The ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound of the present invention has certain thermally-stabilised scope, 205 Can stable existence below DEG C.

Preparation side as a kind of ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound of a second aspect of the present invention Method, adds di-nbutyltin oxide, salicylyl hydrazine, 2-butanone acid and solvent without water beetle in the reaction vessel having nitrogen to protect Alcohol, reacts 5 ~ 24 h, cooling under conditions of temperature is 45 ~ 65 DEG C, filters, and controls solvent volatilization under conditions of 20 ~ 35 DEG C Crystallization, obtains yellow transparent crystal, is ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound.

The preparation characteristic of the ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound of the present invention is: be easy to get from relatively easy Raw material set out, without the separation of intermediate, directly obtain baroque molecule, i.e. one kettle way;Such reaction is in economy In upper and environmental friendliness advantageously.

In a preferred embodiment of the invention, described di-nbutyltin oxide, salicylyl hydrazine, 2-butanone acid three The amount of material 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 di-n-butyl oxidation Stannum adds 15 ~ and 35 milliliters.

A kind of ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound as a third aspect of the present invention is anti-in preparation Application in cancer drug.

Applicant has carried out Anticancer Activity in vitro to above-mentioned ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound and has determined Research, it is thus identified that ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound has certain anticancer bioactive, say, that The purposes of above-mentioned coordination compound is the application in preparing cancer therapy drug, be exactly specifically prepare anti-human pulmonary carcinoma, people's hepatocarcinoma and Application in human breast carcinoma medicine.

The ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound of the present invention is to human lung carcinoma cell, human liver cancer cell and people Breast cancer cell demonstrates good active anticancer, and the ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound of the present invention is anticancer The features such as activity height, low cost, preparation method are simple, provide new way for developing new cancer therapy drug.

Accompanying drawing explanation

Fig. 1 is the IR spectrogram of ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound.

Fig. 2 is ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound1H NMR spectra.

Fig. 3 is ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound13C NMR spectra.

Fig. 4 is the crystal structure figure of ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound.

Fig. 5 is the TG-DTG curve of ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound.

Detailed description of the invention

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

Embodiment 1:

The preparation of ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound:

0.249g (1.0mmol) di-nbutyltin oxide, 0.152g is added in the 100mL there-necked flask having nitrogen to protect (1.0mmol) salicylyl hydrazine, the acid of 0.112g (1.1mmol) 2-butanone and 15mL solvent absolute methanol, be 45 ~ 65 DEG C in temperature Under conditions of react 8 h, cooling, filter, under conditions of 20 ~ 35 DEG C control solvent volatilization crystallization, obtain yellow transparent crystal, i.e. For ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound.Productivity: 85.3%.Fusing point: 205 ~ 207 DEG C (dec).

Elementary analysis (C19H28N2O4Sn): value of calculation: C 48.85, H 6.04, N 6.00;Measured value: C 48.90, H 6.00, N 6.02.

FT-IR (KBr, ν/cm-1): 3053, 3018, 2956, 2924, 2872, 1614, 1598, 1519, 1489, 1456, 1330, 1255, 1205, 1168, 1087, 831, 754, 673, 603, 534, 516, 443。

1H NMR (500 MHz, CDCl3, δ/ppm): 11.94 (s, 1H), 8.07~8.09 (m, 1H), 7.45 ~7.48 (m, 1H), 7.02 (d, J =8.2 Hz, 1H), 6.95~7.03 (t, J =7.5 Hz, 1H), 3.01~ 3.05 (q, J =7.6 Hz, 2H), 1.63~1.66 (m, 4H), 1.46~1.48 (m, 4H), 1.27~1.31 (m, 7H), 0.84 (t, J =7.6 Hz, 6H)。

13C NMR (126 MHz, CDCl3, δ/ppm): 175.75, 165.72, 160.71, 157.59, 134.85, 130.29, 119.21, 117.52, 115.32, 26.81, 26.30, 25.04, 21.19, 13.47, 9.88。

Crystallographic data: monoclinic system, space group C2/c, a=2.37834 (9) nm, b=0.87817 (3) nm, c =2.34607 (9) nm, α=γ=90 °, β=118.4680 (10) °, Z=8, V=4.3075 (3) nm3, Dc= 1.441 Mg·m-3, m (MoK α)=1.210 mm-1, F (000)=1904.

Embodiment 2:

The preparation of ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound:

0.249g (1.0mmol) di-nbutyltin oxide, 0.152g is added in the 100mL there-necked flask having nitrogen to protect (1.0mmol) salicylyl hydrazine, the acid of 0.107g (1.05mmol) 2-butanone and 35mL solvent absolute methanol, be 45 ~ 65 DEG C in temperature Under conditions of react 5 h, cooling, filter, under conditions of 20 ~ 35 DEG C control solvent volatilization crystallization, obtain yellow transparent crystal, i.e. For ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound.Productivity: 87.5%.Fusing point: 205 ~ 207 DEG C (dec).

Elementary analysis (C19H28N2O4Sn): value of calculation: C 48.85, H 6.04, N 6.00;Measured value: C 48.90, H 6.00, N 6.02.

FT-IR (KBr, ν/cm-1): 3053, 3018, 2956, 2924, 2872, 1614, 1598, 1519, 1489, 1456, 1330, 1255, 1205, 1168, 1087, 831, 754, 673, 603, 534, 516, 443。

1H NMR (500 MHz, CDCl3, δ/ppm): 11.94 (s, 1H), 8.07~8.09 (m, 1H), 7.45 ~7.48 (m, 1H), 7.02 (d, J =8.2 Hz, 1H), 6.95~7.03 (t, J =7.5 Hz, 1H), 3.01~ 3.05 (q, J =7.6 Hz, 2H), 1.63~1.66 (m, 4H), 1.46~1.48 (m, 4H), 1.27~1.31 (m, 7H), 0.84 (t, J =7.6 Hz, 6H)。

13C NMR (126 MHz, CDCl3, δ/ppm): 175.75, 165.72, 160.71, 157.59, 134.85, 130.29, 119.21, 117.52, 115.32, 26.81, 26.30, 25.04, 21.19, 13.47, 9.88。

Crystallographic data: monoclinic system, space group C2/c, a=2.37834 (9) nm, b=0.87817 (3) nm, c =2.34607 (9) nm, α=γ=90 °, β=118.4680 (10) °, Z=8, V=4.3075 (3) nm3, Dc= 1.441 Mg·m-3, m (MoK α)=1.210 mm-1, F (000)=1904.

Embodiment 3:

The preparation of ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound:

0.249g (1.0mmol) di-nbutyltin oxide, 0.160g is added in the 100mL there-necked flask having nitrogen to protect (1.05mmol) salicylyl hydrazine, the acid of 0.117g (1.15mmol) 2-butanone and 25mL solvent absolute methanol, be 45 ~ 65 in temperature 24 h are reacted under conditions of DEG C, cooling, filter, under conditions of 20 ~ 35 DEG C, control solvent volatilization crystallization, obtain yellow transparent brilliant Body, is ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound.Productivity: 84.2%.Fusing point: 205 ~ 207 DEG C (dec).

Elementary analysis (C19H28N2O4Sn): value of calculation: C 48.85, H 6.04, N 6.00;Measured value: C 48.90, H 6.00, N 6.02.

FT-IR (KBr, ν/cm-1): 3053, 3018, 2956, 2924, 2872, 1614, 1598, 1519, 1489, 1456, 1330, 1255, 1205, 1168, 1087, 831, 754, 673, 603, 534, 516, 443。

1H NMR (500 MHz, CDCl3, δ/ppm): 11.94 (s, 1H), 8.07~8.09 (m, 1H), 7.45 ~7.48 (m, 1H), 7.02 (d, J =8.2 Hz, 1H), 6.95~7.03 (t, J =7.5 Hz, 1H), 3.01~ 3.05 (q, J =7.6 Hz, 2H), 1.63~1.66 (m, 4H), 1.46~1.48 (m, 4H), 1.27~1.31 (m, 7H), 0.84 (t, J =7.6 Hz, 6H)。

13C NMR (126 MHz, CDCl3, δ/ppm): 175.75, 165.72, 160.71, 157.59, 134.85, 130.29, 119.21, 117.52, 115.32, 26.81, 26.30, 25.04, 21.19, 13.47, 9.88。

Crystallographic data: monoclinic system, space group C2/c, a=2.37834 (9) nm, b=0.87817 (3) nm, c =2.34607 (9) nm, α=γ=90 °, β=118.4680 (10) °, Z=8, V=4.3075 (3) nm3, Dc= 1.441 Mg·m-3, m (MoK α)=1.210 mm-1, F (000)=1904.

Embodiment 4:

The preparation of ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound:

2.490g (10.0mmol) di-nbutyltin oxide, 1.566g is added in the 500mL there-necked flask having nitrogen to protect (10.3mmol) salicylyl hydrazine, the acid of 1.122g (11.0mmol) 2-butanone and 200mL solvent absolute methanol, be 45 ~ 65 in temperature 22 h are reacted under conditions of DEG C, cooling, filter, under conditions of 20 ~ 35 DEG C, control solvent volatilization crystallization, obtain yellow transparent brilliant Body, is ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound.Productivity: 81.7%.Fusing point: 205 ~ 207 DEG C (dec).

Elementary analysis (C19H28N2O4Sn): value of calculation: C 48.85, H 6.04, N 6.00;Measured value: C 48.90, H 6.00, N 6.02.

FT-IR (KBr, ν/cm-1): 3053, 3018, 2956, 2924, 2872, 1614, 1598, 1519, 1489, 1456, 1330, 1255, 1205, 1168, 1087, 831, 754, 673, 603, 534, 516, 443。

1H NMR (500 MHz, CDCl3, δ/ppm): 11.94 (s, 1H), 8.07~8.09 (m, 1H), 7.45 ~7.48 (m, 1H), 7.02 (d, J =8.2 Hz, 1H), 6.95~7.03 (t, J =7.5 Hz, 1H), 3.01~ 3.05 (q, J =7.6 Hz, 2H), 1.63~1.66 (m, 4H), 1.46~1.48 (m, 4H), 1.27~1.31 (m, 7H), 0.84 (t, J =7.6 Hz, 6H)。

13C NMR (126 MHz, CDCl3, δ/ppm): 175.75, 165.72, 160.71, 157.59, 134.85, 130.29, 119.21, 117.52, 115.32, 26.81, 26.30, 25.04, 21.19, 13.47, 9.88。

Crystallographic data: monoclinic system, space group C2/c, a=2.37834 (9) nm, b=0.87817 (3) nm, c =2.34607 (9) nm, α=γ=90 °, β=118.4680 (10) °, Z=8, V=4.3075 (3) nm3, Dc= 1.441 Mg·m-3, m (MoK α)=1.210 mm-1, F (000)=1904.

Test example:

The ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound of the present invention, it is real by MTT that its Anticancer Activity in vitro measures Proved recipe method realizes.

MTT analytic process:

With metabolism reduction 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide it is Basis.Succinate dehydrogenase in living cells mitochondrion 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 is without 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 by microplate reader, can indirectly reflect living cells quantity.

Mtt assay is used to measure the ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound of embodiment 1 preparation to people's lung Cancerous cell (H460), human liver cancer cell (HepG2) and the inhibitory activity of 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, at 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, be not added with testing medicine) and blank group (only adding cultivation medicine, be not added with cell and test medicine).Orifice plate after dosing is put In 37 DEG C, 5%CO2Incubator is cultivated 72h.The activity of control drug measures according to the method for test sample.Cultivating 72h After orifice plate in, 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, and vibrate 5min, makes Formazan crystallization dissolve.Finally, utilize automatic microplate reader at 570nm The optical density in each hole is detected at wavelength.

Data process: data process and use Graph Pad Prism version 7.0 program, coordination compound IC50Pass through journey The nonlinear regression model (NLRM) in sequence with S-shaped 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, result is as shown in table 1, and conclusion is: from data in table, with the 2-carbonyl of the present invention Butanoic acid salicyloyl hydrazone di-n-butyl tin coordination compound is used as cancer therapy drug, to human lung carcinoma cell (H460), human liver cancer cell (HepG2) With human breast cancer cell (MCF7), there is certain drug effect, can be as the candidate compound of cancer therapy drug.

Table 1 ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound cancer therapy drug external activity test data.

People's pulmonary carcinoma People's hepatocarcinoma Human breast carcinoma Cell strain H460 HepG2 MCF7 IC50(μM) 2.52±0.20 1.50±0.68 1.73±0.59

ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound prepared by remaining embodiment with mtt assay to human lung carcinoma cell (H460), human liver cancer cell (HepG2) and the same test example of active anticancer method of testing of human breast cancer cell (MCF7), test knot Fruit 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 change, modification without departing from the spirit and scope of the present invention to the present invention.If to the present invention's These amendments and modification belong within the scope of the claims in the present invention and equivalent technologies thereof, belong to the protection model of the present invention Enclose.

Claims (9)

1. an ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound, for the coordination compound of following structure formula (I):
(I)
Wherein R is normal-butyl.
2. as claimed in claim 1 containing a kind of ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound, its infrared spectrum Data: FT-IR (KBr, ν/cm-1): 3053, 3018, 2956, 2924, 2872, 1614, 1598, 1519, 1489, 1456, 1330, 1255, 1205, 1168, 1087, 831, 754, 673, 603, 534, 516, 443; Its nuclear-magnetism modal data:1H NMR (500 MHz, CDCl3, δ/ppm): 11.94 (s, 1H), 8.07~8.09 (m, 1H), 7.45~7.48 (m, 1H), 7.02 (d, J =8.2 Hz, 1H), 6.95~7.03 (t, J =7.5 Hz, 1H), 3.01~3.05 (q, J =7.6 Hz, 2H), 1.63~1.66 (m, 4H), 1.46~1.48 (m, 4H), 1.27~1.31 (m, 7H), 0.84 (t, J=7.6 Hz, 6H);13C NMR (126 MHz, CDCl3, δ/ppm): 175.75, 165.72, 160.71, 157.59, 134.85, 130.29, 119.21, 117.52, 115.32, 26.81, 26.30, 25.04, 21.19, 13.47, 9.88。
3. ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound as claimed in claim 1, wherein, described 2-carbonyl Butanoic acid salicyloyl hydrazone di-n-butyl tin coordination compound is crystal structure, and its crystallographic data is as follows: monoclinic system, space group C2/c, a =2.37834 (9) nm, b=0.87817 (3) nm, c=2.34607 (9) nm, α=γ=90 °, β=118.4680 (10) °, Z=8, V=4.3075 (3) nm3, Dc=1.441 Mg m-3, m (MoK α)=1.210 mm-1, F (000)= 1904;In molecule, tin atom is hexa-coordinate distorted octahedron configuration.
4. described in claim 1, ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound has certain thermally-stabilised scope, Less than 205 DEG C can stable existence.
5. the preparation method of the ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound described in claim 1, is characterized in that Have in the reaction vessel that nitrogen protects and add di-nbutyltin oxide, salicylyl hydrazine, 2-butanone acid and solvent absolute methanol, in temperature Degree reacts 5 ~ 24 h, cooling under conditions of being 45 ~ 65 DEG C, filter, and controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, Yellow transparent crystal, is ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound.
6. the method for preparation as claimed in claim 5, it is characterised in that described di-nbutyltin oxide, salicylyl hydrazine, 2-fourth The amount of the material of keto acid three is than for 1:(1 ~ 1.05): (1.05 ~ 1.15).
7. the method for preparation as claimed in claim 5, it is characterised in that described solvent absolute methanol consumption is every mM two Normal-butyl stannum oxide adds 15 ~ and 35 milliliters.
8. ALPHA-ketobutyric acid salicyloyl hydrazone di-n-butyl tin coordination compound application in preparing cancer therapy drug described in claim 1.
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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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102060869A (en) * 2010-12-14 2011-05-18 聊城大学 Tindiphenyl (IV) coordination compound of benzoylformic acid-3-hydroxyl-2-naphthyl formyl hydrazone as well as preparation method and application thereof
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
CN105601663A (en) * 2015-11-11 2016-05-25 衡阳师范学院 2-carbonyl-2-phenyl acetic acid salicylyl hydrazone tindiphenyl complex, and preparation method and applications thereof
CN105646568A (en) * 2016-04-11 2016-06-08 衡阳师范学院 2-oxo-propionic acid salicyloyl hydrazone diphenyltin complex as well as preparation method and application thereof

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102060869A (en) * 2010-12-14 2011-05-18 聊城大学 Tindiphenyl (IV) coordination compound of benzoylformic acid-3-hydroxyl-2-naphthyl formyl hydrazone as well as preparation method and application thereof
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
CN105601663A (en) * 2015-11-11 2016-05-25 衡阳师范学院 2-carbonyl-2-phenyl acetic acid salicylyl hydrazone tindiphenyl complex, and preparation method and applications thereof
CN105646568A (en) * 2016-04-11 2016-06-08 衡阳师范学院 2-oxo-propionic acid salicyloyl hydrazone diphenyltin complex as well as preparation method and application thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
FOO I. P. P.等,: "Synthesis and structural characterization of organotin(IV) complexes of pyruvic acid-4-hydroxybenzhydrazone (H4PDB): X-ray crystal structure of nBu2Sn(H2PDB)", 《ACGC CHEMICAL RESEARCH COMMUNICATIONS》 *
S. W. FOO等: "Synthesis and characterization of novel diorganotin(IV) complexes derived from N-benzoylhydrazinoacetic acid methyl ester: X-ray crystal structure of [Ph2Sn(MPB)]", 《ACGC CHEMICAL RESEARCH COMMUNICATIONS》 *

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