CN106220668B - A kind of 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex and its preparation method and application - Google Patents
A kind of 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex and its preparation method and application Download PDFInfo
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- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/22—Tin compounds
- C07F7/2284—Compounds with one or more Sn-N linkages
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/22—Tin compounds
- C07F7/2296—Purification, stabilisation, isolation
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- C07B2200/13—Crystalline forms, e.g. polymorphs
Abstract
The invention discloses a kind of 3 phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complexs of 2 carbonyl, are the complex of following structure formula (I), wherein Ph is phenyl, and R is normal-butyl.The invention also discloses the preparation method of 2 carbonyl, the 3 phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complex and the applications in preparing anticancer drug.
Description
Technical field
The present invention relates to a kind of 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex and preparation method thereof,
And the application of the 2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complexs 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.1980, 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, 2016,804: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
Select salicylyl hydrazine, Sodium.beta.-phenylpyruvate reacts under certain condition with di-nbutyltin oxide, synthesis obtained to human lung carcinoma cell
(H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) have the complex of certain inhibitory activity, anti-to develop
Cancer drug provides new approach.
Invention content
There is provided a kind of 2- carbonyls -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tins to coordinate for the first object of the present invention
Object.
The second object of the present invention is to provide above-mentioned 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex system
Preparation Method.
The third object of the present invention is to provide above-mentioned 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex and exists
Prepare the application in anticancer drug.
As a kind of 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex of the first aspect of the present invention,
For the complex of structure formula (I)
(I)
Wherein Ph is phenyl, and R is normal-butyl.
The present invention 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex through elemental analysis, infrared spectrum,
Nuclear magnetic resoance spectrum and X-ray single crystal diffraction structural analysis, it is as a result as follows：
Elemental analysis (C24H30N2O4Sn)：Calculated value：C 54.47, H 5.71, N 5.29；Measured value：C 54.50, H
5.70, N 5.26.
FT-IR (KBr, ν/cm-1): 3450, 3059, 2960, 2926, 2860, 1616, 1598, 1510,
1490, 1452, 1381, 1323, 1174, 858, 754, 713, 682, 632, 586, 511, 428。
1H NMR (500 MHz, CDCl3, δ/ppm): 11.72 (s, 1H), 7.99~8.01 (d, J =7.9
Hz, 1H), 7.44~7.47 (m, 3H), 7.28~7.31 (m, 2H), 7.21~7.24 (m, 1H), 7.02~7.04
(m, 1H), 6.94~6.97 (t, J =7.6 Hz, 1H), 4.35 (s, 2H), 1.57~1.66 (m, 4H), 1.45~
1.51 (m, 4H), 1.21~1.28 (m, 4H), 0.78~0.81 (t, J =7.3 Hz, 6H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 175.86, 164.22, 160.73, 154.94,
135.05, 133.89, 130.15, 129.37, 128.99, 127.40, 119.27, 117.68, 115.08,
33.48, 26.57, 26.36, 22.74, 13.39。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -100.08。
2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin the complexs of the present invention are crystal structure, and crystal is
Monoclinic system, space group P2 (1)/n, a=1.33587 (7) nm, b=0.93905 (5) nm, c=1.88594 (9) nm, α
=γ=90 °, β=90.0310 (10) °, Z=4, V=2.3658 (2) nm3, the Mgm of Dc=1.486-3, m (MoK α)=
1.111 mm-1, F (000)=1080.
2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin the complexs of the present invention are structurally characterized in that：In molecule
Tin atom is hexa-coordinate distorted octahedron configuration.
2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin the complexs of the present invention have certain thermostabilization model
It encloses, can be stabilized at 164 DEG C or less.
A kind of 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex as the second aspect of the present invention
Di-nbutyltin oxide, salicylyl hydrazine, Sodium.beta.-phenylpyruvate and solvent is added in preparation method in the reaction vessel for having nitrogen protection
Absolute methanol reacts 5 ~ 24 h under conditions of temperature is 45 ~ 65 DEG C, cooling, and filtering controls molten under conditions of 20 ~ 35 DEG C
Agent volatilization crystallization, obtains yellow transparent crystal, as 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex.
The preparation characteristic of 2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complexs of the present invention is：From opposite
Raw material simple and easy to get sets out, and without the separation of intermediate, directly obtains complicated molecule, i.e. one kettle way；It is such anti-
It answers on economically and environmentally close friend advantageously.
In a preferred embodiment of the invention, the di-nbutyltin oxide, salicylyl hydrazine, Sodium.beta.-phenylpyruvate three
Substance amount ratio be 1:(1~1.05):(1.05~1.15).
In a preferred embodiment of the invention, the solvent absolute methanol dosage is that every mM of di-n-butyl aoxidizes
Tin adds 15 ~ 35 milliliters.
A kind of 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex as the third aspect of the present invention exists
Prepare the application in anticancer drug.
Applicant has carried out external anticancer to above-mentioned 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex and has lived
Property determine research, it is thus identified that 2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complexs have certain Anti-cancer biologic
Activity, that is to say, that the purposes of above-mentioned complex is the application in preparing anticancer drug, be exactly specifically prepare it is anti-human
Application in lung cancer, human liver cancer and human breast carcinoma drug.
2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin the complexs of the present invention are to human lung carcinoma cell, human liver cancer
Cell and human breast cancer cell show good active anticancer, and 2- carbonyl -3- phenylpropionic acids salicyloyl hydrazone two of the invention is just
The features such as butyl tin complex active anticancer is high, at low cost, preparation method is simple, the anticancer drug to develop new provide new way
Diameter.
Description of the drawings
Fig. 1 is the IR spectrograms of 2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complexs.
Fig. 2 is 2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complexs1H NMR spectras.
Fig. 3 is 2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complexs13C NMR spectras.
Fig. 4 is 2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complexs119Sn NMR spectras.
Fig. 5 is the crystal structure figure of 2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complexs.
Fig. 6 is the TG-DTG curves of 2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complexs.
Specific implementation mode
By detailed description below, invention is further described in detail.
Embodiment 1：
The preparation of 2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complexs：
In the 100mL three-necked flasks for having nitrogen protection be added 0.249g (1.0mmol) di-nbutyltin oxide,
0.152g (1.0mmol) salicylyl hydrazine, 0.205g (1.1mmol) Sodium.beta.-phenylpyruvates and 15mL solvent absolute methanols, in temperature
8 h are reacted under conditions of being 45 ~ 65 DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, it is saturating to obtain yellow
Bright crystal, as 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex.Yield：83.3%.Fusing point：164~166
℃(dec)。
Elemental analysis (C24H30N2O4Sn)：Calculated value：C 54.47, H 5.71, N 5.29；Measured value：C 54.50, H
5.70, N 5.26.
FT-IR (KBr, ν/cm-1): 3450, 3059, 2960, 2926, 2860, 1616, 1598, 1510,
1490, 1452, 1381, 1323, 1174, 858, 754, 713, 682, 632, 586, 511, 428。
1H NMR (500 MHz, CDCl3, δ/ppm): 11.72 (s, 1H), 7.99~8.01 (d, J =7.9
Hz, 1H), 7.44~7.47 (m, 3H), 7.28~7.31 (m, 2H), 7.21~7.24 (m, 1H), 7.02~7.04
(m, 1H), 6.94~6.97 (t, J =7.6 Hz, 1H), 4.35 (s, 2H), 1.57~1.66 (m, 4H), 1.45~
1.51 (m, 4H), 1.21~1.28 (m, 4H), 0.78~0.81 (t, J =7.3 Hz, 6H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 175.86, 164.22, 160.73, 154.94,
135.05, 133.89, 130.15, 129.37, 128.99, 127.40, 119.27, 117.68, 115.08,
33.48, 26.57, 26.36, 22.74, 13.39。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -100.08。
Crystallographic data：Monoclinic system, space group P2 (1)/n, a=1.33587 (7) nm, b=0.93905 (5) nm,
C=1.88594 (9) nm, α=γ=90 °, β=90.0310 (10) °, Z=4, V=2.3658 (2) nm3, Dc=
1.486 Mg·m-3, m (MoK α)=1.111 mm-1, F (000)=1080.
Embodiment 2：
The preparation of 2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complexs：
In the 100mL three-necked flasks for having nitrogen protection be added 0.249g (1.0mmol) di-nbutyltin oxide,
0.152g (1.0mmol) salicylyl hydrazine, 0.195g (1.05mmol) Sodium.beta.-phenylpyruvates and 35mL solvent absolute methanols, in temperature
5 h are reacted under conditions of being 45 ~ 65 DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, it is saturating to obtain yellow
Bright crystal, as 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex.Yield：85.5%.Fusing point：164~166
℃(dec)。
Elemental analysis (C24H30N2O4Sn)：Calculated value：C 54.47, H 5.71, N 5.29；Measured value：C 54.50, H
5.70, N 5.26.
FT-IR (KBr, ν/cm-1): 3450, 3059, 2960, 2926, 2860, 1616, 1598, 1510,
1490, 1452, 1381, 1323, 1174, 858, 754, 713, 682, 632, 586, 511, 428。
1H NMR (500 MHz, CDCl3, δ/ppm): 11.72 (s, 1H), 7.99~8.01 (d, J =7.9
Hz, 1H), 7.44~7.47 (m, 3H), 7.28~7.31 (m, 2H), 7.21~7.24 (m, 1H), 7.02~7.04
(m, 1H), 6.94~6.97 (t, J =7.6 Hz, 1H), 4.35 (s, 2H), 1.57~1.66 (m, 4H), 1.45~
1.51 (m, 4H), 1.21~1.28 (m, 4H), 0.78~0.81 (t, J =7.3 Hz, 6H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 175.86, 164.22, 160.73, 154.94,
135.05, 133.89, 130.15, 129.37, 128.99, 127.40, 119.27, 117.68, 115.08,
33.48, 26.57, 26.36, 22.74, 13.39。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -100.08。
Crystallographic data：Monoclinic system, space group P2 (1)/n, a=1.33587 (7) nm, b=0.93905 (5) nm,
C=1.88594 (9) nm, α=γ=90 °, β=90.0310 (10) °, Z=4, V=2.3658 (2) nm3, Dc=
1.486 Mg·m-3, m (MoK α)=1.111 mm-1, F (000)=1080.
Embodiment 3：
The preparation of 2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complexs：
In the 100mL three-necked flasks for having nitrogen protection be added 0.249g (1.0mmol) di-nbutyltin oxide,
0.160g (1.05mmol) salicylyl hydrazine, 0.214g (1.15mmol) Sodium.beta.-phenylpyruvates and 25mL solvent absolute methanols, in temperature
Degree reacts 24 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 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex.Yield：84.1%.Fusing point：164~
166℃(dec)。
Elemental analysis (C24H30N2O4Sn)：Calculated value：C 54.47, H 5.71, N 5.29；Measured value：C 54.50, H
5.70, N 5.26.
FT-IR (KBr, ν/cm-1): 3450, 3059, 2960, 2926, 2860, 1616, 1598, 1510,
1490, 1452, 1381, 1323, 1174, 858, 754, 713, 682, 632, 586, 511, 428。
1H NMR (500 MHz, CDCl3, δ/ppm): 11.72 (s, 1H), 7.99~8.01 (d, J =7.9
Hz, 1H), 7.44~7.47 (m, 3H), 7.28~7.31 (m, 2H), 7.21~7.24 (m, 1H), 7.02~7.04
(m, 1H), 6.94~6.97 (t, J =7.6 Hz, 1H), 4.35 (s, 2H), 1.57~1.66 (m, 4H), 1.45~
1.51 (m, 4H), 1.21~1.28 (m, 4H), 0.78~0.81 (t, J =7.3 Hz, 6H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 175.86, 164.22, 160.73, 154.94,
135.05, 133.89, 130.15, 129.37, 128.99, 127.40, 119.27, 117.68, 115.08,
33.48, 26.57, 26.36, 22.74, 13.39。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -100.08。
Crystallographic data：Monoclinic system, space group P2 (1)/n, a=1.33587 (7) nm, b=0.93905 (5) nm,
C=1.88594 (9) nm, α=γ=90 °, β=90.0310 (10) °, Z=4, V=2.3658 (2) nm3, Dc=
1.486 Mg·m-3, m (MoK α)=1.111 mm-1, F (000)=1080.
Embodiment 4：
The preparation of 2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complexs：
In the 500mL three-necked flasks for having nitrogen protection be added 2.490g (10.0mmol) di-nbutyltin oxide,
1.566g (10.3mmol) salicylyl hydrazine, 2.046g (11.0mmol) Sodium.beta.-phenylpyruvates and 200mL solvent absolute methanols, in temperature
Degree reacts 22 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 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex.Yield：81.1%.Fusing point：164~
166℃(dec)。
Elemental analysis (C24H30N2O4Sn)：Calculated value：C 54.47, H 5.71, N 5.29；Measured value：C 54.50, H
5.70, N 5.26.
FT-IR (KBr, ν/cm-1): 3450, 3059, 2960, 2926, 2860, 1616, 1598, 1510,
1490, 1452, 1381, 1323, 1174, 858, 754, 713, 682, 632, 586, 511, 428。
1H NMR (500 MHz, CDCl3, δ/ppm): 11.72 (s, 1H), 7.99~8.01 (d, J =7.9
Hz, 1H), 7.44~7.47 (m, 3H), 7.28~7.31 (m, 2H), 7.21~7.24 (m, 1H), 7.02~7.04
(m, 1H), 6.94~6.97 (t, J =7.6 Hz, 1H), 4.35 (s, 2H), 1.57~1.66 (m, 4H), 1.45~
1.51 (m, 4H), 1.21~1.28 (m, 4H), 0.78~0.81 (t, J =7.3 Hz, 6H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 175.86, 164.22, 160.73, 154.94,
135.05, 133.89, 130.15, 129.37, 128.99, 127.40, 119.27, 117.68, 115.08,
33.48, 26.57, 26.36, 22.74, 13.39。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -100.08。
Crystallographic data：Monoclinic system, space group P2 (1)/n, a=1.33587 (7) nm, b=0.93905 (5) nm,
C=1.88594 (9) nm, α=γ=90 °, β=90.0310 (10) °, Z=4, V=2.3658 (2) nm3, Dc=
1.486 Mg·m-3, m (MoK α)=1.111 mm-1, F (000)=1080.
Test example：
2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin the complexs of the present invention, Anticancer Activity in vitro measure
It is realized by MTT experiment method.
MTT analytic approach：
3- (4,5-Dimethylthiazol-2-yl) -2,5-diphenyltetrazolium is restored with metabolism
Based on bromide.Succinate dehydrogenase in living cells mitochondria can make exogenous MTT be reduced to the bluish violet of water-insoluble
Crystallization first a ceremonial jade-ladle, used in libation (Formazan) is simultaneously deposited in cell, and dead cell is without this function.Dimethyl sulfoxide (DMSO) (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.
2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin the complexs of the preparation of embodiment 1 are measured using mtt assay
To the inhibitory activity of human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7).
Cell strain and cultivating system：H460, HepG2 and MCF7 cell strain are derived from American tissue incubator (ATCC).With containing
RPMI 1640 (GIBICO 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
Base -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complexs are used as anticancer drug, thin to human lung carcinoma cell (H460), human liver cancer
Born of the same parents (HepG2) and human breast cancer cell (MCF7) have certain drug effect, can be used as the candidate compound of anticancer drug.
1 2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complex anticancer drug external activity test numbers of table
According to.
| Human lung cancer | Human liver cancer | Human breast carcinoma | |
| Cell strain | H460 | HepG2 | MCF7 |
| IC50(μM) | 3.59±0.17 | 1.69±0.61 | 1.99±0.42 |
2- carbonyl -3- phenylpropionic acid salicyloyl hydrazone di-n-butyl tin complexs prepared by remaining embodiment are with mtt assay to people
The active anticancer test method of lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) is the same as experiment
Example, 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. a kind of 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex is the complex of following structure formula (I)：
(I)
Wherein Ph is phenyl, and R is normal-butyl；The complex (I) is crystal structure, and crystallographic data is as follows：Monoclinic crystal
System, space group P2 (1)/n, a=1.33587 (7) nm, b=0.93905 (5) nm, c=1.88594 (9) nm, α=γ
=90 °, β=90.0310 (10) °, Z=4, V=2.3658 (2) nm3, the Mgm of Dc=1.486-3, m (MoK α)=1.111
mm-1, F (000)=1080；Tin atom is hexa-coordinate distorted octahedron configuration in molecule；The infrared light of the complex (I)
Modal data：FT-IR (KBr, ν/cm-1): 3450, 3059, 2960, 2926, 2860, 1616, 1598, 1510,
1490, 1452, 1381, 1323, 1174, 858, 754, 713, 682, 632, 586, 511, 428；Nuclear-magnetism composes number
According to：1H NMR (500 MHz, CDCl3, δ/ppm): 11.72 (s, 1H), 7.99~8.01 (d, J =7.9 Hz,
1H), 7.44~7.47 (m, 3H), 7.28~7.31 (m, 2H), 7.21~7.24 (m, 1H), 7.02~7.04 (m,
1H), 6.94~6.97 (t, J =7.6 Hz, 1H), 4.35 (s, 2H), 1.57~1.66 (m, 4H), 1.45~1.51
(m, 4H), 1.21~1.28 (m, 4H), 0.78~0.81 (t, J=7.3 Hz, 6H)；13C NMR (126 MHz,
CDCl3, δ/ppm): 175.86, 164.22, 160.73, 154.94, 135.05, 133.89, 130.15,
129.37, 128.99, 127.40, 119.27, 117.68, 115.08, 33.48, 26.57, 26.36, 22.74,
13.39；119Sn NMR (187 MHz, CDCl3, δ/ppm): -100.08；The complex (I) is in 164 DEG C or less energy
It is stabilized.
2. the preparation method of 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex described in claim 1, special
Sign is that addition di-nbutyltin oxide, salicylyl hydrazine, Sodium.beta.-phenylpyruvate and solvent are anhydrous in the reaction vessel for having nitrogen protection
Methanol reacts 5 ~ 24 h under conditions of temperature is 45 ~ 65 DEG C, cooling, filtering, and controlling solvent under conditions of 20 ~ 35 DEG C waves
Hair crystallization, obtains yellow transparent crystal, as 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex.
3. preparation method as claimed in claim 2, which is characterized in that the di-nbutyltin oxide, salicylyl hydrazine, propiophenone
The amount ratio of the substance of sour sodium three is 1:(1~1.05):(1.05~1.15).
4. preparation method as claimed in claim 2, which is characterized in that the solvent absolute methanol dosage be every mM two just
Butyl tin oxide adds 15 ~ 35 milliliters.
5. 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex is in preparing anticancer drug described in claim 1
Application.
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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