CN106220671A - A kind of 2 carbonyl 2 phenylacetic acids are to toluyl hydrazone stannous phenide coordination compound and its preparation method and application - Google Patents
A kind of 2 carbonyl 2 phenylacetic acids are to toluyl hydrazone stannous phenide coordination compound and its preparation method and application Download PDFInfo
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- CN106220671A CN106220671A CN201610716472.6A CN201610716472A CN106220671A CN 106220671 A CN106220671 A CN 106220671A CN 201610716472 A CN201610716472 A CN 201610716472A CN 106220671 A CN106220671 A CN 106220671A
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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
- 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
- C07F7/22—Tin compounds
- C07F7/2296—Purification, stabilisation, isolation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Abstract
The invention discloses a kind of 2 carbonyl 2 phenylacetic acids to toluyl hydrazone stannous phenide coordination compound, for the coordination compound of following structure formula (I), wherein Ph is phenyl.The invention also discloses this 2 carbonyl 2 phenylacetic acid to the preparation method of toluyl hydrazone stannous phenide coordination compound and the application in preparing cancer therapy drug.
Description
Technical field
The present invention relates to a kind of 2-carbonyl-2-phenylacetic acid to toluyl hydrazone stannous phenide coordination compound and preparation side thereof
Method, and this 2-carbonyl-2-phenylacetic acid is to the application in preparing cancer therapy drug of the 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 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
Selecting and react toluyl hydrazine, benzoyl formic acid under certain condition with diphenyl stannum dichloride, synthesis has obtained people's lung
Cancerous cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) have the coordination compound of certain inhibitory activity, for
Exploitation cancer therapy drug provides new approach.
Summary of the invention
The first object of the present invention there is provided a kind of 2-carbonyl-2-phenylacetic acid and joins toluyl hydrazone stannous phenide
Compound.
The second object of the present invention is to provide above-mentioned 2-carbonyl-2-phenylacetic acid and coordinates toluyl hydrazone stannous phenide
Thing preparation method.
The third object of the present invention is to provide above-mentioned 2-carbonyl-2-phenylacetic acid and coordinates toluyl hydrazone stannous phenide
Thing application in preparing cancer therapy drug.
Toluyl hydrazone stannous phenide is coordinated by a kind of 2-carbonyl-2-phenylacetic acid as a first aspect of the present invention
Thing, for the coordination compound of structure formula (I)
(I)
Wherein Ph is phenyl.
2-carbonyl-2-the phenylacetic acid of the present invention to toluyl hydrazone stannous phenide coordination compound through elementary analysis, infrared
Spectrum, nuclear magnetic resoance spectrum and X-ray single crystal diffraction structural analysis, result is as follows:
Elementary analysis (C112H88N8O12Sn4): value of calculation: C 60.79, H 4.01, N 5.06；Measured value: C 60.83, H
4.04, N 5.05.
FT-IR (KBr, ν/cm-1): 3631, 3051, 2989, 2920, 2862, 1689, 1629, 1597,
1581, 1564, 1494, 1475, 1392, 1338, 1323, 1249, 1178, 1159, 1089, 1020, 821,
750, 731, 694, 640, 619, 596, 478, 453。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.17-8.20 (m, 4H), 7.86-7.88 (m, 4H),
7.48-7.54 (m, 9H), 7.30 (d, J = 7.9 Hz, 2H), 2.45 (s, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 175.45, 163.11, 149.62, 143.85,
136.22, 135.83, 132.36, 131.75, 131.43, 129.41, 129.35, 129.28, 128.95,
128.41, 127.69, 21.84。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.03。
2-carbonyl-2-the phenylacetic acid of the present invention is crystal structure to toluyl hydrazone stannous phenide coordination compound, and it is brilliant
Body is: anorthic system, space group P-1, a=1.27277 (12) nm, b=1.38116 (13) nm, c=1.59531 (14)
Nm, α=69.8880 (10) °, β=75.8280 (10) °, γ=72.0020 (10) °, Z=1, V=2.4742 (4) nm3, Dc
= 1.496 Mg·m-3, m (MoK α)=1.065 mm-1, F (000)=1120.
Toluyl hydrazone stannous phenide coordination compound is structurally characterized in that by the 2-carbonyl-2-phenylacetic acid of the present invention: point
In son, tin atom is hexa-coordinate distorted octahedron configuration.
Toluyl hydrazone stannous phenide coordination compound is had certain thermally-stabilised by the 2-carbonyl-2-phenylacetic acid of the present invention
Scope, can stable existence below 204 DEG C.
Toluyl hydrazone stannous phenide is coordinated by a kind of 2-carbonyl-2-phenylacetic acid as a second aspect of the present invention
The preparation method of thing, adds diphenyl stannum dichloride, to toluyl hydrazine, benzoyl in the reaction vessel having nitrogen to protect
Formic acid and solvent 95% methanol, react 5 ~ 24 h, cooling under conditions of temperature is 45 ~ 65 DEG C, filter, the condition of 20 ~ 35 DEG C
The volatilization crystallization of lower control solvent, obtains yellow transparent crystal, is 2-carbonyl-2-phenylacetic acid to toluyl hydrazone stannous phenide
Coordination compound.
The preparation characteristic of toluyl hydrazone stannous phenide coordination compound is by the 2-carbonyl-2-phenylacetic acid of the present invention: from
The relatively easy raw material being easy to get sets out, and without the separation of intermediate, directly obtains baroque molecule, i.e. one kettle way；So
Reaction economically and environmentally close friend on advantageously.
In a preferred embodiment of the invention, described diphenyl stannum dichloride, to toluyl hydrazine, benzoyl first
The amount of the material of acid three ratio is for 1:(1 ~ 1.05): (1.05 ~ 1.15).
In a preferred embodiment of the invention, described solvent 95% methanol usage is every mM of diphenyl dichloride
Stannum adds 15 ~ and 35 milliliters.
Toluyl hydrazone stannous phenide is coordinated by a kind of 2-carbonyl-2-phenylacetic acid as a third aspect of the present invention
Thing application in preparing cancer therapy drug.
Applicant has carried out In Vitro Anti to above-mentioned 2-carbonyl-2-phenylacetic acid to toluyl hydrazone stannous phenide coordination compound
Cancer activity determines research, it is thus identified that toluyl hydrazone stannous phenide coordination compound is had certain by 2-carbonyl-2-phenylacetic acid
Anticancer bioactive, say, that the purposes of above-mentioned coordination compound is the application in preparing cancer therapy drug, be exactly specifically
Prepare the application in anti-human pulmonary carcinoma, people's hepatocarcinoma and human breast carcinoma medicine.
2-carbonyl-2-the phenylacetic acid of the present invention to toluyl hydrazone stannous phenide coordination compound to human lung carcinoma cell, people
Hepatoma carcinoma cell and human breast cancer cell demonstrate good active anticancer, and the 2-carbonyl-2-phenylacetic acid of the present invention is to methylbenzene
The features such as formyl hydrazone stannous phenide coordination compound active anticancer height, low cost, preparation method are simple, carry for developing new cancer therapy drug
Supply new way.
Accompanying drawing explanation
Fig. 1 is the 2-carbonyl-2-phenylacetic acid IR spectrogram to toluyl hydrazone stannous phenide coordination compound.
Fig. 2 is that 2-carbonyl-2-phenylacetic acid is to toluyl hydrazone stannous phenide coordination compound1H NMR spectra.
Fig. 3 is that 2-carbonyl-2-phenylacetic acid is to toluyl hydrazone stannous phenide coordination compound13C NMR spectra.
Fig. 4 is that 2-carbonyl-2-phenylacetic acid is to toluyl hydrazone stannous phenide coordination compound119Sn NMR spectra.
Fig. 5 is the 2-carbonyl-2-phenylacetic acid crystal structure figure to toluyl hydrazone stannous phenide coordination compound.
Fig. 6 is the 2-carbonyl-2-phenylacetic acid TG-DTG curve to toluyl hydrazone stannous phenide coordination compound.
Detailed description of the invention
By detailed description below, the present invention is described in further detail.
Embodiment 1:
The preparation to toluyl hydrazone stannous phenide coordination compound of the 2-carbonyl-2-phenylacetic acid:
0.344g (1.0mmol) diphenyl stannum dichloride, 0.150g is added in the 100mL there-necked flask having nitrogen to protect
(1.0mmol) to toluyl hydrazine, 0.165g (1.1mmol) benzoyl formic acid and 15mL solvent 95% methanol, in temperature it is
8 h are reacted under conditions of 45 ~ 65 DEG C, cooling, filter, under conditions of 20 ~ 35 DEG C, control solvent volatilization crystallization, obtain yellow transparent
Crystal, is 2-carbonyl-2-phenylacetic acid to toluyl hydrazone stannous phenide coordination compound.Productivity: 84.6%.Fusing point: 204 ~
206℃(dec)。
Elementary analysis (C112H88N8O12Sn4): value of calculation: C 60.79, H 4.01, N 5.06；Measured value: C 60.83, H
4.04, N 5.05.
FT-IR (KBr, ν/cm-1): 3631, 3051, 2989, 2920, 2862, 1689, 1629, 1597,
1581, 1564, 1494, 1475, 1392, 1338, 1323, 1249, 1178, 1159, 1089, 1020, 821,
750, 731, 694, 640, 619, 596, 478, 453。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.17-8.20 (m, 4H), 7.86-7.88 (m, 4H),
7.48-7.54 (m, 9H), 7.30 (d, J = 7.9 Hz, 2H), 2.45 (s, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 175.45, 163.11, 149.62, 143.85,
136.22, 135.83, 132.36, 131.75, 131.43, 129.41, 129.35, 129.28, 128.95,
128.41, 127.69, 21.84。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.03。
Crystallographic data: anorthic system, space group P-1, a=1.27277 (12) nm, b=1.38116 (13) nm, c
=1.59531 (14) nm, α=69.8880 (10) °, β=75.8280 (10) °, γ=72.0020 (10) °, Z=1, V=
2.4742(4) nm3, Dc=1.496 Mg m-3, m (MoK α)=1.065 mm-1, F (000)=1120.
Embodiment 2:
The preparation to toluyl hydrazone stannous phenide coordination compound of the 2-carbonyl-2-phenylacetic acid:
0.344g (1.0mmol) diphenyl stannum dichloride, 0.150g is added in the 100mL there-necked flask having nitrogen to protect
(1.0mmol) to toluyl hydrazine, 0.157g (1.05mmol) benzoyl formic acid and 35mL solvent 95% methanol, in temperature it is
5 h are reacted under conditions of 45 ~ 65 DEG C, cooling, filter, under conditions of 20 ~ 35 DEG C, control solvent volatilization crystallization, obtain yellow transparent
Crystal, is 2-carbonyl-2-phenylacetic acid to toluyl hydrazone stannous phenide coordination compound.Productivity: 86.5%.Fusing point: 204 ~
206℃(dec)。
Elementary analysis (C112H88N8O12Sn4): value of calculation: C 60.79, H 4.01, N 5.06；Measured value: C 60.83, H
4.04, N 5.05.
FT-IR (KBr, ν/cm-1): 3631, 3051, 2989, 2920, 2862, 1689, 1629, 1597,
1581, 1564, 1494, 1475, 1392, 1338, 1323, 1249, 1178, 1159, 1089, 1020, 821,
750, 731, 694, 640, 619, 596, 478, 453。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.17-8.20 (m, 4H), 7.86-7.88 (m, 4H),
7.48-7.54 (m, 9H), 7.30 (d, J = 7.9 Hz, 2H), 2.45 (s, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 175.45, 163.11, 149.62, 143.85,
136.22, 135.83, 132.36, 131.75, 131.43, 129.41, 129.35, 129.28, 128.95,
128.41, 127.69, 21.84。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.03。
Crystallographic data: anorthic system, space group P-1, a=1.27277 (12) nm, b=1.38116 (13) nm, c
=1.59531 (14) nm, α=69.8880 (10) °, β=75.8280 (10) °, γ=72.0020 (10) °, Z=1, V=
2.4742(4) nm3, Dc=1.496 Mg m-3, m (MoK α)=1.065 mm-1, F (000)=1120.
Embodiment 3:
The preparation to toluyl hydrazone stannous phenide coordination compound of the 2-carbonyl-2-phenylacetic acid:
0.344g (1.0mmol) diphenyl stannum dichloride, 0.157g is added in the 100mL there-necked flask having nitrogen to protect
(1.05mmol) to toluyl hydrazine, 0.173g (1.15mmol) benzoyl formic acid and 25mL solvent 95% methanol, in temperature
24 h are reacted under conditions of being 45 ~ 65 DEG C, cooling, filter, under conditions of 20 ~ 35 DEG C, control solvent volatilization crystallization, obtain yellow
Transparent crystal, is 2-carbonyl-2-phenylacetic acid to toluyl hydrazone stannous phenide coordination compound.Productivity: 87.0%.Fusing point:
204~206℃(dec)。
Elementary analysis (C112H88N8O12Sn4): value of calculation: C 60.79, H 4.01, N 5.06；Measured value: C 60.83, H
4.04, N 5.05.
FT-IR (KBr, ν/cm-1): 3631, 3051, 2989, 2920, 2862, 1689, 1629, 1597,
1581, 1564, 1494, 1475, 1392, 1338, 1323, 1249, 1178, 1159, 1089, 1020, 821,
750, 731, 694, 640, 619, 596, 478, 453。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.17-8.20 (m, 4H), 7.86-7.88 (m, 4H),
7.48-7.54 (m, 9H), 7.30 (d, J = 7.9 Hz, 2H), 2.45 (s, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 175.45, 163.11, 149.62, 143.85,
136.22, 135.83, 132.36, 131.75, 131.43, 129.41, 129.35, 129.28, 128.95,
128.41, 127.69, 21.84。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.03。
Crystallographic data: anorthic system, space group P-1, a=1.27277 (12) nm, b=1.38116 (13) nm, c
=1.59531 (14) nm, α=69.8880 (10) °, β=75.8280 (10) °, γ=72.0020 (10) °, Z=1, V=
2.4742(4) nm3, Dc=1.496 Mg m-3, m (MoK α)=1.065 mm-1, F (000)=1120.
Embodiment 4:
The preparation to toluyl hydrazone stannous phenide coordination compound of the 2-carbonyl-2-phenylacetic acid:
3.440g (10.0mmol) diphenyl stannum dichloride, 1.545g is added in the 500mL there-necked flask having nitrogen to protect
(10.3mmol) to toluyl hydrazine, 1.650g (11.0mmol) benzoyl formic acid and 210mL solvent 95% methanol, in temperature
22 h are reacted under conditions of being 45 ~ 65 DEG C, cooling, filter, under conditions of 20 ~ 35 DEG C, control solvent volatilization crystallization, obtain yellow
Transparent crystal, is 2-carbonyl-2-phenylacetic acid to toluyl hydrazone stannous phenide coordination compound.Productivity: 82.3%.Fusing point:
204~206℃(dec)。
Elementary analysis (C112H88N8O12Sn4): value of calculation: C 60.79, H 4.01, N 5.06；Measured value: C 60.83, H
4.04, N 5.05.
FT-IR (KBr, ν/cm-1): 3631, 3051, 2989, 2920, 2862, 1689, 1629, 1597,
1581, 1564, 1494, 1475, 1392, 1338, 1323, 1249, 1178, 1159, 1089, 1020, 821,
750, 731, 694, 640, 619, 596, 478, 453。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.17-8.20 (m, 4H), 7.86-7.88 (m, 4H),
7.48-7.54 (m, 9H), 7.30 (d, J = 7.9 Hz, 2H), 2.45 (s, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 175.45, 163.11, 149.62, 143.85,
136.22, 135.83, 132.36, 131.75, 131.43, 129.41, 129.35, 129.28, 128.95,
128.41, 127.69, 21.84。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -294.03。
Crystallographic data: anorthic system, space group P-1, a=1.27277 (12) nm, b=1.38116 (13) nm, c
=1.59531 (14) nm, α=69.8880 (10) °, β=75.8280 (10) °, γ=72.0020 (10) °, Z=1, V=
2.4742(4) nm3, Dc=1.496 Mg m-3, m (MoK α)=1.065 mm-1, F (000)=1120.
Test example:
Toluyl hydrazone stannous phenide coordination compound, its Anticancer Activity in vitro are measured by the 2-carbonyl-2-phenylacetic acid of the present invention
Realized by MTT experiment method.
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.
Toluyl hydrazone stannous phenide is joined by the 2-carbonyl-2-phenylacetic acid using mtt assay to measure embodiment 1 preparation
Compound is to human lung carcinoma 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
Base-2-phenylacetic acid is used as cancer therapy drug to toluyl hydrazone stannous phenide coordination compound, to human lung carcinoma cell (H460), people liver
Cancerous cell (HepG2) and human breast cancer cell (MCF7) have certain drug effect, can be as the candidate compound of cancer therapy drug.
Toluyl hydrazone stannous phenide coordination compound cancer therapy drug external activity is tested by table 1 2-carbonyl-2-phenylacetic acid
Data.
| People's pulmonary carcinoma | People's hepatocarcinoma | Human breast carcinoma | |
| Cell strain | H460 | HepG2 | MCF7 |
| IC50(μM) | 1.40±0.25 | 0.62±0.20 | 0.74±0.17 |
2-carbonyl-2-phenylacetic acid prepared by remaining embodiment to toluyl hydrazone stannous phenide coordination compound with mtt assay
Same to the active anticancer method of testing of human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7)
Test example, 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 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. 2-carbonyl-2-phenylacetic acid is to a toluyl hydrazone stannous phenide coordination compound, for the cooperation of following structure formula (I)
Thing:
(I)
Wherein Ph is phenyl.
2. toluyl hydrazone stannous phenide is coordinated by the one 2-carbonyl-2-phenylacetic acid that contains as claimed in claim 1
Thing, its ir data: FT-IR (KBr, ν/cm-1): 3631, 3051, 2989, 2920, 2862, 1689,
1629, 1597, 1581, 1564, 1494, 1475, 1392, 1338, 1323, 1249, 1178, 1159, 1089,
1020, 821, 750, 731, 694, 640, 619, 596, 478, 453；Its nuclear-magnetism modal data:1H NMR (500
MHz, CDCl3, δ/ppm): 8.17-8.20 (m, 4H), 7.86-7.88 (m, 4H), 7.48-7.54 (m, 9H),
7.30 (d, J= 7.9 Hz, 2H), 2.45 (s, 3H)；13C NMR (126 MHz, CDCl3, δ/ppm):
175.45, 163.11, 149.62, 143.85, 136.22, 135.83, 132.36, 131.75, 131.43,
129.41, 129.35, 129.28, 128.95, 128.41, 127.69, 21.84；119Sn NMR (187 MHz,
CDCl3, δ/ppm): -294.03。
3. 2-carbonyl-2-phenylacetic acid as claimed in claim 1 is to toluyl hydrazone stannous phenide coordination compound, wherein, institute
2-carbonyl-2-the phenylacetic acid stated is crystal structure to toluyl hydrazone stannous phenide coordination compound, and its crystallographic data is as follows:
Anorthic system, space group P-1, a=1.27277 (12) nm, b=1.38116 (13) nm, c=1.59531 (14) nm, α=
69.8880 (10) °, β=75.8280 (10) °, γ=72.0020 (10) °, Z=1, V=2.4742 (4) nm3, Dc=1.496
Mg·m-3, m (MoK α)=1.065 mm-1, F (000)=1120；In molecule, tin atom is hexa-coordinate distorted octahedron configuration.
4. 2-carbonyl-2-phenylacetic acid described in claim 1 has certain heat to toluyl hydrazone stannous phenide coordination compound
Stability range, can stable existence below 204 DEG C.
5. the preparation side to toluyl hydrazone stannous phenide coordination compound of the 2-carbonyl-2-phenylacetic acid described in claim 1
Method, is characterized in that adding diphenyl stannum dichloride in the reaction vessel having nitrogen to protect, to toluyl hydrazine, benzoyl first
Acid and solvent 95% methanol, react 5 ~ 24 h, cooling under conditions of temperature is 45 ~ 65 DEG C, filter, under conditions of 20 ~ 35 DEG C
Control solvent volatilization crystallization, obtain yellow transparent crystal, be 2-carbonyl-2-phenylacetic acid and toluyl hydrazone stannous phenide is joined
Compound.
6. the method for preparation as claimed in claim 5, it is characterised in that described diphenyl stannum dichloride, to toluyl
Hydrazine, benzoyl formic acid three the amount of material 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 95% methanol usage is every mM two
Phenyl dichloro stannum adds 15 ~ and 35 milliliters.
8. toluyl hydrazone stannous phenide coordination compound is being prepared anticarcinogen by 2-carbonyl-2-phenylacetic acid described in claim 1
Application in thing.
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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