CN106220669B - A kind of dialkyl tin complex of the ligand containing acylhydrazone and its preparation method and application - Google Patents
A kind of dialkyl tin complex of the ligand containing acylhydrazone and its preparation method and application Download PDFInfo
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- CN106220669B CN106220669B CN201610709360.8A CN201610709360A CN106220669B CN 106220669 B CN106220669 B CN 106220669B CN 201610709360 A CN201610709360 A CN 201610709360A CN 106220669 B CN106220669 B CN 106220669B
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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
It is the complex of following structure formula (I) the invention discloses a kind of 2 carbonyl propionic acids to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex, wherein Ph is phenyl, and R is to methylbenzyl.The invention also discloses 2 carbonyl propionic acids to preparation method of the tert-butyl benzoyl hydrazone two to methylbenzyl tin complex and the application in preparing anticancer drug.
Description
Technical field
The present invention relates to a kind of 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex and its preparation
Method and the 2- carbonyl propionic acids are to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex answering in preparing anticancer drug
With.
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
It selects and tert-butyl benzoyl hydrazine, Sodium Pyruvate is reacted under certain condition with two pairs of methylbenzyl stannous chloride, synthesis obtains
There is certain inhibitory activity to match human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7)
Object is closed, new approach is provided for exploitation anticancer drug.
Invention content
The first object of the present invention is there is provided a kind of 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to methylbenzyl tin
Complex.
The second object of the present invention is to provide above-mentioned 2- carbonyl propionic acids and matches to methylbenzyl tin to tert-butyl benzoyl hydrazone two
Close object preparation method.
The third object of the present invention is to provide above-mentioned 2- carbonyl propionic acids and matches to methylbenzyl tin to tert-butyl benzoyl hydrazone two
Close application of the object in preparing anticancer drug.
A kind of 2- carbonyl propionic acids as the first aspect of the present invention match methylbenzyl tin tert-butyl benzoyl hydrazone two
Object is closed, is the complex of structure formula (I)
(I)
Wherein Ph is phenyl, and R is to methylbenzyl.
The 2- carbonyl propionic acids of the present invention are to tert-butyl benzoyl hydrazone two to methylbenzyl 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 (C62H76N4O8Sn2)：Calculated value：C 59.92, H 6.16, N 4.51；Measured value：C 59.95, H
6.13, N 4.52.
FT-IR (KBr, ν/cm-1): 3666, 3327, 3045, 2960, 2866, 1606, 1510, 1487,
1392, 1325, 1205, 1192, 1163, 1972, 921, 850, 815, 765, 719, 596, 555, 540,
503, 460, 418。
1H NMR (500 MHz, CDCl3, δ/ppm): 7.95 (d, J = 8.2 Hz, 2H), 7.47 (d, J =
8.4 Hz, 2H), 7.29 (d, J = 7.8 Hz, 1H), 7.20 (d, J = 7.8 Hz, 1H), 6.87 (m,
6H), 3.10 (s, 4H), 2.20 (s, 6H), 2.11(s, 3H), 1.38(s, 9H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.71, 155.83, 138.48, 135.03,
132.65, 129.27, 129.23, 129.10, 128.40, 127.96, 125.20, 50.89, 35.09, 31.20,
21.24, 20.91, 13.06。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -509.34。
The 2- carbonyl propionic acids of the present invention are crystal structure to methylbenzyl tin complex to tert-butyl benzoyl hydrazone two, brilliant
Body is monoclinic system, space group P2 (1)/c, a=1.82997 (7) nm, b=0.87001 (3) nm, c=1.92944 (7)
Nm, α=γ=90 °, β=90.5960 (10) °, Z=4, V=3.07168 (19) nm3, the Mgm of Dc=1.344-3, m (MoK
α)= 0.867 mm-1, F (000)=1280.
The 2- carbonyl propionic acids of the present invention are structurally characterized in that methylbenzyl tin complex tert-butyl benzoyl hydrazone two：Point
Tin atom is seven coordination distortion pentagonal bipyramid configurations in son.
The 2- carbonyl propionic acids of the present invention have certain heat steady methylbenzyl tin complex tert-butyl benzoyl hydrazone two
Determine range, can be stabilized at 98 DEG C or less.
A kind of 2- carbonyl propionic acids as the second aspect of the present invention match methylbenzyl tin tert-butyl benzoyl hydrazone two
Two pairs of methylbenzyl stannous chloride are added, to tert-butyl benzene first in the preparation method for closing object in the reaction vessel for having nitrogen protection
Hydrazides, Sodium Pyruvate and solvent absolute methanol react 5 ~ 24 h under conditions of temperature is 45 ~ 75 DEG C, cooling, filtering, 20 ~
Solvent volatilization crystallization is controlled under conditions of 35 DEG C, obtains yellow transparent crystal, as 2- carbonyl propionic acids are to tert-butyl benzoyl hydrazone two
To methylbenzyl tin complex.
The present invention 2- carbonyl propionic acids be to the preparation characteristic of methylbenzyl tin complex to tert-butyl benzoyl hydrazone two：From
The relatively easy raw material being easy to get sets out, and without the separation of intermediate, directly obtains complicated molecule, i.e. one kettle way；In this way
Reaction economically and environmentally close friend on advantageously.
In a preferred embodiment of the invention, two pairs of methylbenzyl stannous chloride, to tert-butyl benzoyl hydrazine,
The amount ratio of the substance of Sodium Pyruvate three is 1:(1~1.05):(1.05~1.15).
In a preferred embodiment of the invention, the solvent absolute methanol dosage is every mM of two pairs of methylbenzyls
Stannous chloride adds 15 ~ 35 milliliters.
A kind of 2- carbonyl propionic acids as the third aspect of the present invention match methylbenzyl tin tert-butyl benzoyl hydrazone two
Close application of the object in preparing anticancer drug.
Applicant has carried out in vitro methylbenzyl tin complex tert-butyl benzoyl hydrazone two above-mentioned 2- carbonyl propionic acids
Active anticancer determines research, it is thus identified that 2- carbonyl propionic acids have methylbenzyl tin complex tert-butyl benzoyl hydrazone two certain
Anticancer bioactive, that is to say, that the purposes of above-mentioned complex is the application in preparing anticancer drug, is exactly specifically
Application in preparing anti-human lung cancer, human liver cancer and human breast carcinoma drug.
The 2- carbonyl propionic acids of the present invention are to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex to human lung carcinoma cell, people
Liver cancer cells and human breast cancer cell show good active anticancer, and 2- carbonyl propionic acids of the invention are to tert-butyl benzoyl hydrazone
The features such as two pairs of methylbenzyl tin complex active anticancers are high, at low cost, preparation method is simple, the anticancer drug to develop new carry
New way is supplied.
Description of the drawings
Fig. 1 is for 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to the IR spectrograms of methylbenzyl tin complex.
Fig. 2 is for 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex1H NMR spectras.
Fig. 3 is for 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex13C NMR spectras.
Fig. 4 is for 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex119Sn NMR spectras.
Fig. 5 is for 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to the crystal structure figure of methylbenzyl tin complex.
Fig. 6 is for 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to the TG-DTG curves of methylbenzyl tin complex.
Specific implementation mode
By detailed description below, invention is further described in detail.
Embodiment 1：
Preparation of the 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex：
0.400g (1.0mmol) two pairs of methylbenzyl dichlorides are added in the 100mL three-necked flasks for having nitrogen protection
Tin, 0.192g (1.0mmol) are to tert-butyl benzoyl hydrazine, 0.121g (1.1mmol) Sodium Pyruvates and 15mL solvents without water beetle
Alcohol reacts 8 h under conditions of temperature is 45 ~ 75 DEG C, cooling, filtering, and solvent volatilization knot is controlled under conditions of 20 ~ 35 DEG C
Crystalline substance, obtains yellow transparent crystal, as 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex.Yield：
77.4%.Fusing point：98~100℃(dec).
Elemental analysis (C62H76N4O8Sn2)：Calculated value：C 59.92, H 6.16, N 4.51；Measured value：C 59.95, H
6.13, N 4.52.
FT-IR (KBr, ν/cm-1): 3666, 3327, 3045, 2960, 2866, 1606, 1510, 1487,
1392, 1325, 1205, 1192, 1163, 1972, 921, 850, 815, 765, 719, 596, 555, 540,
503, 460, 418。
1H NMR (500 MHz, CDCl3, δ/ppm): 7.95 (d, J = 8.2 Hz, 2H), 7.47 (d, J =
8.4 Hz, 2H), 7.29 (d, J = 7.8 Hz, 1H), 7.20 (d, J = 7.8 Hz, 1H), 6.87 (m,
6H), 3.10 (s, 4H), 2.20 (s, 6H), 2.11(s, 3H), 1.38(s, 9H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.71, 155.83, 138.48, 135.03,
132.65, 129.27, 129.23, 129.10, 128.40, 127.96, 125.20, 50.89, 35.09, 31.20,
21.24, 20.91, 13.06。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -509.34。
Crystallographic data：Monoclinic system, space group P2 (1)/c, a=1.82997 (7) nm, b=0.87001 (3)
Nm, c=1.92944 (7) nm, α=γ=90 °, β=90.5960 (10) °, Z=4, V=3.07168 (19) nm3, Dc=
1.344 Mg·m-3, m (MoK α)=0.867 mm-1, F (000)=1280.
Embodiment 2：
Preparation of the 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex：
0.400g (1.0mmol) two pairs of methylbenzyl dichlorides are added in the 100mL three-necked flasks for having nitrogen protection
Tin, 0.192g (1.0mmol) are to tert-butyl benzoyl hydrazine, 0.115g (1.05mmol) Sodium Pyruvates and 35mL solvents without water beetle
Alcohol reacts 5 h under conditions of temperature is 45 ~ 75 DEG C, cooling, filtering, and solvent volatilization knot is controlled under conditions of 20 ~ 35 DEG C
Crystalline substance, obtains yellow transparent crystal, as 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex.Yield：
78.3%.Fusing point：98~100℃(dec).
Elemental analysis (C62H76N4O8Sn2)：Calculated value：C 59.92, H 6.16, N 4.51；Measured value：C 59.95, H
6.13, N 4.52.
FT-IR (KBr, ν/cm-1): 3666, 3327, 3045, 2960, 2866, 1606, 1510, 1487,
1392, 1325, 1205, 1192, 1163, 1972, 921, 850, 815, 765, 719, 596, 555, 540,
503, 460, 418。
1H NMR (500 MHz, CDCl3, δ/ppm): 7.95 (d, J = 8.2 Hz, 2H), 7.47 (d, J =
8.4 Hz, 2H), 7.29 (d, J = 7.8 Hz, 1H), 7.20 (d, J = 7.8 Hz, 1H), 6.87 (m,
6H), 3.10 (s, 4H), 2.20 (s, 6H), 2.11(s, 3H), 1.38(s, 9H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.71, 155.83, 138.48, 135.03,
132.65, 129.27, 129.23, 129.10, 128.40, 127.96, 125.20, 50.89, 35.09, 31.20,
21.24, 20.91, 13.06。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -509.34。
Crystallographic data：Monoclinic system, space group P2 (1)/c, a=1.82997 (7) nm, b=0.87001 (3)
Nm, c=1.92944 (7) nm, α=γ=90 °, β=90.5960 (10) °, Z=4, V=3.07168 (19) nm3, Dc=
1.344 Mg·m-3, m (MoK α)=0.867 mm-1, F (000)=1280.
Embodiment 3：
Preparation of the 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex：
0.400g (1.0mmol) two pairs of methylbenzyl dichlorides are added in the 100mL three-necked flasks for having nitrogen protection
Tin, 0.202g (1.05mmol) are anhydrous to tert-butyl benzoyl hydrazine, 0.126g (1.15mmol) Sodium Pyruvates and 25mL solvents
Methanol reacts 24 h under conditions of temperature is 45 ~ 75 DEG C, cooling, filtering, and solvent volatilization is controlled under conditions of 20 ~ 35 DEG C
Crystallization, obtains yellow transparent crystal, as 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex.Yield：
76.0%.Fusing point：98~100℃(dec).
Elemental analysis (C62H76N4O8Sn2)：Calculated value：C 59.92, H 6.16, N 4.51；Measured value：C 59.95, H
6.13, N 4.52.
FT-IR (KBr, ν/cm-1): 3666, 3327, 3045, 2960, 2866, 1606, 1510, 1487,
1392, 1325, 1205, 1192, 1163, 1972, 921, 850, 815, 765, 719, 596, 555, 540,
503, 460, 418。
1H NMR (500 MHz, CDCl3, δ/ppm): 7.95 (d, J = 8.2 Hz, 2H), 7.47 (d, J =
8.4 Hz, 2H), 7.29 (d, J = 7.8 Hz, 1H), 7.20 (d, J = 7.8 Hz, 1H), 6.87 (m,
6H), 3.10 (s, 4H), 2.20 (s, 6H), 2.11(s, 3H), 1.38(s, 9H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.71, 155.83, 138.48, 135.03,
132.65, 129.27, 129.23, 129.10, 128.40, 127.96, 125.20, 50.89, 35.09, 31.20,
21.24, 20.91, 13.06。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -509.34。
Crystallographic data：Monoclinic system, space group P2 (1)/c, a=1.82997 (7) nm, b=0.87001 (3)
Nm, c=1.92944 (7) nm, α=γ=90 °, β=90.5960 (10) °, Z=4, V=3.07168 (19) nm3, Dc=
1.344 Mg·m-3, m (MoK α)=0.867 mm-1, F (000)=1280.
Embodiment 4：
Preparation of the 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex：
4.000g (10.0mmol) two pairs of methylbenzyl dichlorides are added in the 500mL three-necked flasks for having nitrogen protection
Tin, 1.978g (10.3mmol) are anhydrous to tert-butyl benzoyl hydrazine, 1.210g (11.0mmol) Sodium Pyruvates and 210mL solvents
Methanol reacts 22 h under conditions of temperature is 45 ~ 75 DEG C, cooling, filtering, and solvent volatilization is controlled under conditions of 20 ~ 35 DEG C
Crystallization, obtains yellow transparent crystal, as 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex.Yield：
71.3%.Fusing point：98~100℃(dec).
Elemental analysis (C62H76N4O8Sn2)：Calculated value：C 59.92, H 6.16, N 4.51；Measured value：C 59.95, H
6.13, N 4.52.
FT-IR (KBr, ν/cm-1): 3666, 3327, 3045, 2960, 2866, 1606, 1510, 1487,
1392, 1325, 1205, 1192, 1163, 1972, 921, 850, 815, 765, 719, 596, 555, 540,
503, 460, 418。
1H NMR (500 MHz, CDCl3, δ/ppm): 7.95 (d, J = 8.2 Hz, 2H), 7.47 (d, J =
8.4 Hz, 2H), 7.29 (d, J = 7.8 Hz, 1H), 7.20 (d, J = 7.8 Hz, 1H), 6.87 (m,
6H), 3.10 (s, 4H), 2.20 (s, 6H), 2.11(s, 3H), 1.38(s, 9H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.71, 155.83, 138.48, 135.03,
132.65, 129.27, 129.23, 129.10, 128.40, 127.96, 125.20, 50.89, 35.09, 31.20,
21.24, 20.91, 13.06。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -509.34。
Crystallographic data：Monoclinic system, space group P2 (1)/c, a=1.82997 (7) nm, b=0.87001 (3)
Nm, c=1.92944 (7) nm, α=γ=90 °, β=90.5960 (10) °, Z=4, V=3.07168 (19) nm3, Dc=
1.344 Mg·m-3, m (MoK α)=0.867 mm-1, F (000)=1280.
Test example：
The 2- carbonyl propionic acids of the present invention are to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex, Anticancer Activity in vitro
Measurement 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.
Using mtt assay come measure embodiment 1 preparation 2- carbonyl propionic acids to tert-butyl benzoyl hydrazone two to methylbenzyl tin
Inhibitory activity of the complex to 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
Propionic acid is used as anticancer drug to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex, to human lung carcinoma cell (H460), people liver
Cancer cell (HepG2) and human breast cancer cell (MCF7) have certain drug effect, can be used as the candidate compound of anticancer drug.
1 2- carbonyl propionic acids of table survey methylbenzyl tin complex anticancer drug external activity tert-butyl benzoyl hydrazone two
Try data.
| Human lung cancer | Human liver cancer | Human breast carcinoma | |
| Cell strain | H460 | HepG2 | MCF7 |
| IC50(μM) | 4.18±0.13 | 1.89±1.55 | 2.41±1.51 |
2- carbonyl propionic acids prepared by remaining embodiment are to tert-butyl benzoyl hydrazone two to methylbenzyl tin complex with mtt assay
It is same to the active anticancer test method of human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7)
Test 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 dialkyl tin complex of ligand containing acylhydrazone is the complex of following structure formula (I)：
(I)
Wherein Ph is phenyl, and R is to methylbenzyl；The complex (I) is crystal structure, and crystallographic data is as follows：It is single
Oblique system, space group P2 (1)/c, a=1.82997 (7) nm, b=0.87001 (3) nm, c=1.92944 (7) nm, α
=γ=90 °, β=90.5960 (10) °, Z=4, V=3.07168 (19) nm3, the Mgm of Dc=1.344-3, m (MoK α)=
0.867 mm-1, F (000)=1280；Tin atom is seven coordination distortion pentagonal bipyramid configurations in molecule；The complex (I)
Ir data：FT-IR (KBr, ν/cm-1): 3666, 3327, 3045, 2960, 2866, 1606, 1510,
1487, 1392, 1325, 1205, 1192, 1163, 1972, 921, 850, 815, 765, 719, 596, 555,
540, 503, 460, 418；Nuclear-magnetism modal data：1H NMR (500 MHz, CDCl3, δ/ppm): 7.95 (d, J = 8.2
Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 7.8 Hz, 1H), 7.20 (d, J = 7.8
Hz, 1H), 6.87 (m, 6H), 3.10 (s, 4H), 2.20 (s, 6H), 2.11(s, 3H), 1.38(s, 9H)；13C NMR (127 MHz, CDCl3, δ/ppm): 174.71, 155.83, 138.48, 135.03, 132.65,
129.27, 129.23, 129.10, 128.40, 127.96, 125.20, 50.89, 35.09, 31.20, 21.24,
20.91, 13.06；119Sn NMR (187 MHz, CDCl3, δ/ppm): -509.34；The complex (I) is at 98 DEG C
It can be stabilized below.
2. the preparation method of the dialkyl tin complex of the ligand described in claim 1 containing acylhydrazone, it is characterized in that there is nitrogen guarantor
In the reaction vessel of shield be added two pairs of methylbenzyl stannous chloride, to tert-butyl benzoyl hydrazine, Sodium Pyruvate and solvent without water beetle
Alcohol reacts 5 ~ 24 h under conditions of temperature is 45 ~ 75 DEG C, and cooling, filtering controls solvent volatilization under conditions of 20 ~ 35 DEG C
Crystallization, obtains yellow transparent crystal, as the dialkyl tin complex of the ligand containing acylhydrazone.
3. preparation method as claimed in claim 2, which is characterized in that two pairs of methylbenzyl stannous chloride, to tertiary butyl
Benzoyl hydrazine, Sodium Pyruvate three substance amount ratio be 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 is two pairs every mM
Methylbenzyl stannous chloride adds 15 ~ 35 milliliters.
5. application of the dialkyl tin complex of the ligand containing acylhydrazone described in claim 1 in preparing anticancer drug.
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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