CN106432324A - 2-carbonyl-3-phenylpropionic acid p-methoxybenzoyl hydrazone dibenzyl stannic complex as well as preparation method and application thereof - Google Patents
2-carbonyl-3-phenylpropionic acid p-methoxybenzoyl hydrazone dibenzyl stannic complex as well as preparation method and application thereof Download PDFInfo
- Publication number
- CN106432324A CN106432324A CN201610747512.3A CN201610747512A CN106432324A CN 106432324 A CN106432324 A CN 106432324A CN 201610747512 A CN201610747512 A CN 201610747512A CN 106432324 A CN106432324 A CN 106432324A
- Authority
- CN
- China
- Prior art keywords
- carbonyl
- phenylpropionic acid
- complex
- methoxybenzoyl
- methoxybenzoyl hydrazone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
Abstract
The invention discloses a 2-carbonyl-3-phenylpropionic acid p-methoxybenzoyl hydrazone dibenzylstannic complex, which is a complex with the following structural formula (I) (which is shown in the description), wherein Ph is phenyl and R is benzyl. The invention further discloses a preparation method of the 2-carbonyl-3-phenylpropionic acid p-methoxybenzoyl hydrazone dibenzylstannic complex and application of the 2-carbonyl-3-phenylpropionic acid p-methoxybenzoyl hydrazone dibenzylstannic complex in preparation of anti-cancer drugs.
Description
Technical field
The present invention relates to a kind of 2-carbonyl-3-phenylpropionic acid to methoxybenzoyl hydrazone Dibenzyltin complex and preparation thereof
Method, and this 2-carbonyl-3-phenylpropionic acid to methoxybenzoyl hydrazone Dibenzyltin complex in preparing cancer therapy drug
Application.
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 mouse and rat.But in 1972, Brown found,
By food or drug administration by injection, triphenyltin acetate Ph3SnOOCCH3Can suppress the tumor growth of mouse, 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 screening valency further
The compound of value.They continue deeper into research, finally found that the tin compound of two organic group coordinations, such as tin-oxide
(R2SnO), tin hydroxide ［ SnR2(OH) X ］ etc. have an antitumor activity, and find out that they all contain or hydrolyze and can produce tin oxygen
Key.1980, Crowe etc. was found that again some organo-tin compounds have preferable active anticancer, from this, resisted with regard to organotin
The research of cancer activity becomes the another focus extremely enlivening after cis-platinum.1989, American National anticancer research institute
(National Cancer Institute) has carried out antitumor activity screening, result table to more than 2,000 kinds of organo-tin compounds
Some organo-tin compounds bright have inhibitory action to P388 lymphocytic leukemia.2002, Gielen et al. was to organic
The activity of tin carboxylate compound has done comprehensive summing up, thinks that many organo-tin compounds have really preferably external after research
Active anticancer.
Research shows, the part of the organic group that organotin atom connects and participation coordination decides organo-tin compound
Biologically active, select some itself have good biological activity organic ligand with in organotin tin atom be coordinated 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 biologically active, stronger joining
Capability and various coordination mode, and have a wide range of applications at aspects such as medicine, agricultural chemicals, material and analytical reagents.Closely
Nian Lai, it is compared in terms of biologically active and in depth studies by many researchers both at home and abroad, research discovery acylhydrazone class
Compound has the various active such as anticancer, sterilization, anti-inflammatory.Therefore, acylhydrazone class Schiff part is combined with organotin, it is intended to
Obtain the higher noval chemical compound of biologically active, become people's research direction interested.
Chinese patent CN 102718794A discloses a kind of double acylhydrazone class Schiff stannous phenide complex 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 complex and
Application in preparation treatment liver cancer, adenocarcinoma of lung, breast cancer, prostate cancer, colon cancer or the early young leukemic medicine of grain.
Document (Journal of Organometallic Chemistry, 2014,75:83-91) report, 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, 2013,724:23-31) reporting, series has
Machine tin 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 cancer cell such as human colon cancer cell (HCT-8), people in loop (hl-60).
Document (Bioorganic ＆ Medicinal Chemistry Letters, 2015,25: 4461- 4463)
Report, the active anticancer to human liver cancer cell (HuH-7) and human lung adenocarcinoma cell (A549) for multiple acylhydrazone class Schiff parts.
Document (Journal of Organometallic Chemistry, 2016,804:48-58) report, 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) inhibitory action of cancer 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 reacting methoxybenzoyl hydrazine, benzoyl formic acid and TriphenylphosphineoxComplex under certain condition, synthesis has obtained to people
Lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) have the complex of certain inhibitory activity,
Provide new approach for developing cancer therapy drug.
Content of the invention
The first object of the present invention there is provided a kind of 2-carbonyl-3-phenylpropionic acid to methoxybenzoyl hydrazone Dibenzyltin
Complex.
The second object of the present invention is to provide above-mentioned 2-carbonyl-3-phenylpropionic acid and joins methoxybenzoyl hydrazone Dibenzyltin
Compound preparation method.
The third object of the present invention is to provide above-mentioned 2-carbonyl-3-phenylpropionic acid and joins methoxybenzoyl hydrazone Dibenzyltin
Application in preparing cancer therapy drug for the compound.
Methoxybenzoyl hydrazone Dibenzyltin is joined by a kind of 2-carbonyl-3-phenylpropionic acid as a first aspect of the present invention
Compound, is the complex of structure formula (I)
(I)
Wherein Ph is phenyl, and R is benzyl.
2-carbonyl-3-the phenylpropionic acid of the present invention to methoxybenzoyl hydrazone Dibenzyltin complex through elementary analysis, red
External spectrum, nuclear magnetic resoance spectrum and X-ray single crystal diffraction structural analysis, result is as follows：
Elementary analysis (C64H64N4O10Sn2)：Calculated value：C 59.24, H 5.01, N 4.35；Measured value：C 59.23, H
5.03, N 4.37.
FT-IR (KBr, ν/cm-1): 3448, 3059, 3024, 2935, 2837, 1681, 1600, 1479,
1388, 1251, 1168, 1028, 844, 759, 698, 646, 590, 569, 522, 459.
1H NMR (500 MHz, CDCl3, δ/ppm): 8.00 (d,J= 8.8 Hz, 2H), 7.32 (m,
2H), 7.27 (m, 2H), 7.20-7.23 (m, 1H), 6.96 (d,J= 8.8 Hz, 2H), 6.83 (s,
10H), 3.91 (s, 3H), 3.88 (s, 2H), 3.48 (s, 3H), 3.17 (d,J= 11.6 Hz, 2H),
3.13 (d,J= 11.6 Hz, 2H).
13C NMR (126 MHz, CDCl3, δ/ppm): 174.74, 168.12, 162.92, 150.78,
136.28, 135.33, 130.85, 129.97, 128.44, 128.20, 128.11, 126.59, 125.49,
125.23, 113.50, 55.43, 50.82, 34.99, 32.17.
119Sn NMR (187 MHz, CDCl3, δ/ppm): -334.35.
2-carbonyl-3-the phenylpropionic acid of the present invention is crystal structure to methoxybenzoyl hydrazone Dibenzyltin complex, its
Crystal is anorthic system, space group P-1, a=1.04461 (12) nm, b=1.17203 (14) nm, c=1.30628
(15) nm, α=84.1900 (10) °, β=71.6100 (10) °, γ=72.6240 (10) °, Z=1, V=1.4483 (3)
nm3, Dc=1.475 Mg m-3, m (MoK α)=0.925 mm-1, F (000)=656.
Methoxybenzoyl hydrazone Dibenzyltin complex is structurally characterized in that by the 2-carbonyl-3-phenylpropionic acid of the present invention：
In molecule, tin atom is seven coordination distortion pentagonal bipyramid configurations.
It is steady that the 2-carbonyl-3-phenylpropionic acid of the present invention has certain heat to methoxybenzoyl hydrazone Dibenzyltin complex
Determine scope, can stable existence below 64 DEG C.
Methoxybenzoyl hydrazone Dibenzyltin is joined by a kind of 2-carbonyl-3-phenylpropionic acid as a second aspect of the present invention
The preparation method of compound, adds TriphenylphosphineoxComplex, to methoxybenzoyl hydrazine, benzene in the reaction vessel having nitrogen to protect
GA and solvent absolute methanol, react 5 ~ 24 h, cooling under conditions of temperature is 45 ~ 65 DEG C, filter, at 20 ~ 35 DEG C
Under conditions of control solvent volatilization crystallization, obtain yellow transparent crystal, be 2-carbonyl-3-phenylpropionic acid to methoxybenzoyl hydrazone
Dibenzyltin complex.
The preparation characteristic to methoxybenzoyl hydrazone Dibenzyltin complex for the 2-carbonyl-3-phenylpropionic acid of the present invention is：
From the relatively easy raw material being easy to get, without the separation of intermediate, directly obtain baroque molecule, i.e. one kettle way；This
On the reaction of sample economically and environmentally close friend advantageously.
In a preferred embodiment of the invention, described TriphenylphosphineoxComplex, to methoxybenzoyl hydrazine, benzoyl
The amount ratio of the material of formic acid three is 1:(1~1.05):(1.05~1.15).
In a preferred embodiment of the invention, described solvent absolute methanol consumption is every mM of dibenzyl dichloride
Tin adds 15 ~ and 35 milliliters.
Methoxybenzoyl hydrazone Dibenzyltin is joined by a kind of 2-carbonyl-3-phenylpropionic acid as a third aspect of the present invention
Application in preparing cancer therapy drug for the compound.
Methoxybenzoyl hydrazone Dibenzyltin complex has been carried out in vitro by applicant by above-mentioned 2-carbonyl-3-phenylpropionic acid
Active anticancer determines research, it is thus identified that 2-carbonyl-3-phenylpropionic acid has one to methoxybenzoyl hydrazone Dibenzyltin complex
Fixed anticancer bioactive, say, that the purposes of above-mentioned complex is the application in preparing cancer therapy drug, specifically
It is the application in preparing anti-human lung cancer, people's liver cancer and human breast carcinoma medicine.
2-carbonyl-3-the phenylpropionic acid of the present invention to methoxybenzoyl hydrazone Dibenzyltin complex to human lung carcinoma cell,
Human liver cancer cell and human breast cancer cell demonstrate good active anticancer, and the 2-carbonyl-3-phenylpropionic acid of the present invention is to methoxy
The features such as base benzoyl hydrazone Dibenzyltin complex active anticancer height, low cost, preparation method are simple, for the new anticarcinogen of exploitation
Thing provides new way.
Brief description
Fig. 1 is the IR spectrogram to methoxybenzoyl hydrazone Dibenzyltin complex for the 2-carbonyl-3-phenylpropionic acid.
Fig. 2 is that 2-carbonyl-3-phenylpropionic acid is to methoxybenzoyl hydrazone Dibenzyltin complex1H NMR spectra.
Fig. 3 is that 2-carbonyl-3-phenylpropionic acid is to methoxybenzoyl hydrazone Dibenzyltin complex13C NMR spectra.
Fig. 4 is that 2-carbonyl-3-phenylpropionic acid is to methoxybenzoyl hydrazone Dibenzyltin complex119Sn NMR spectra.
Fig. 5 is the crystal structure figure to methoxybenzoyl hydrazone Dibenzyltin complex for the 2-carbonyl-3-phenylpropionic acid.
Fig. 6 is the TG-DTG curve to methoxybenzoyl hydrazone Dibenzyltin complex for the 2-carbonyl-3-phenylpropionic acid.
Detailed description of the invention
By detailed description below, the present invention is described in further detail.
Embodiment 1：
The preparation to methoxybenzoyl hydrazone Dibenzyltin complex for the 2-carbonyl-3-phenylpropionic acid：
0.372g (1.0mmol) TriphenylphosphineoxComplex, 0.166g is added in the 100mL there-necked flask having nitrogen to protect
(1.0mmol) to methoxybenzoyl hydrazine, 0.165g (1.1mmol) benzoyl formic acid and 15mL solvent absolute methanol, in temperature
It is under conditions of 45 ~ 65 DEG C, to react 8 h, cooling, filter, under conditions of 20 ~ 35 DEG C, control solvent volatilization crystallization, obtain yellow saturating
Bright crystal, is 2-carbonyl-3-phenylpropionic acid to methoxybenzoyl hydrazone Dibenzyltin complex.Productivity：76.0%.Fusing point：64
~66℃(dec).
Elementary analysis (C64H64N4O10Sn2)：Calculated value：C 59.24, H 5.01, N 4.35；Measured value：C 59.23, H
5.03, N 4.37.
FT-IR (KBr, ν/cm-1): 3448, 3059, 3024, 2935, 2837, 1681, 1600, 1479,
1388, 1251, 1168, 1028, 844, 759, 698, 646, 590, 569, 522, 459.
1H NMR (500 MHz, CDCl3, δ/ppm): 8.00 (d,J= 8.8 Hz, 2H), 7.32 (m,
2H), 7.27 (m, 2H), 7.20-7.23 (m, 1H), 6.96 (d,J= 8.8 Hz, 2H), 6.83 (s,
10H), 3.91 (s, 3H), 3.88 (s, 2H), 3.48 (s, 3H), 3.17 (d,J= 11.6 Hz, 2H),
3.13 (d,J= 11.6 Hz, 2H).
13C NMR (126 MHz, CDCl3, δ/ppm): 174.74, 168.12, 162.92, 150.78,
136.28, 135.33, 130.85, 129.97, 128.44, 128.20, 128.11, 126.59, 125.49,
125.23, 113.50, 55.43, 50.82, 34.99, 32.17.
119Sn NMR (187 MHz, CDCl3, δ/ppm): -334.35.
Crystallographic data：Anorthic system, space group P-1, a=1.04461 (12) nm, b=1.17203 (14) nm,
C=1.30628 (15) nm, α=84.1900 (10) °, β=71.6100 (10) °, γ=72.6240 (10) °, Z=1, V=
1.4483(3) nm3, Dc=1.475 Mg m-3, m (MoK α)=0.925 mm-1, F (000)=656.
Embodiment 2：
The preparation to methoxybenzoyl hydrazone Dibenzyltin complex for the 2-carbonyl-3-phenylpropionic acid：
0.372g (1.0mmol) TriphenylphosphineoxComplex, 0.166g is added in the 100mL there-necked flask having nitrogen to protect
(1.0mmol) to methoxybenzoyl hydrazine, 0.157g (1.05mmol) benzoyl formic acid and 35mL solvent absolute methanol, in temperature
Degree is to react 5 h under conditions of 45 ~ 65 DEG C, cooling, filters, and controls solvent volatilization crystallization, obtain yellow under conditions of 20 ~ 35 DEG C
Transparent crystal, is 2-carbonyl-3-phenylpropionic acid to methoxybenzoyl hydrazone Dibenzyltin complex.Productivity：77.8%.Fusing point：
64~66℃(dec).
Elementary analysis (C64H64N4O10Sn2)：Calculated value：C 59.24, H 5.01, N 4.35；Measured value：C 59.23, H
5.03, N 4.37.
FT-IR (KBr, ν/cm-1): 3448, 3059, 3024, 2935, 2837, 1681, 1600, 1479,
1388, 1251, 1168, 1028, 844, 759, 698, 646, 590, 569, 522, 459.
1H NMR (500 MHz, CDCl3, δ/ppm): 8.00 (d,J= 8.8 Hz, 2H), 7.32 (m,
2H), 7.27 (m, 2H), 7.20-7.23 (m, 1H), 6.96 (d,J= 8.8 Hz, 2H), 6.83 (s,
10H), 3.91 (s, 3H), 3.88 (s, 2H), 3.48 (s, 3H), 3.17 (d,J= 11.6 Hz, 2H),
3.13 (d,J= 11.6 Hz, 2H).
13C NMR (126 MHz, CDCl3, δ/ppm): 174.74, 168.12, 162.92, 150.78,
136.28, 135.33, 130.85, 129.97, 128.44, 128.20, 128.11, 126.59, 125.49,
125.23, 113.50, 55.43, 50.82, 34.99, 32.17.
119Sn NMR (187 MHz, CDCl3, δ/ppm): -334.35.
Crystallographic data：Anorthic system, space group P-1, a=1.04461 (12) nm, b=1.17203 (14) nm,
C=1.30628 (15) nm, α=84.1900 (10) °, β=71.6100 (10) °, γ=72.6240 (10) °, Z=1, V=
1.4483(3) nm3, Dc=1.475 Mg m-3, m (MoK α)=0.925 mm-1, F (000)=656.
Embodiment 3：
The preparation to methoxybenzoyl hydrazone Dibenzyltin complex for the 2-carbonyl-3-phenylpropionic acid：
0.372g (1.0mmol) TriphenylphosphineoxComplex, 0.174g is added in the 100mL there-necked flask having nitrogen to protect
(1.05mmol) to methoxybenzoyl hydrazine, 0.173g (1.15mmol) benzoyl formic acid and 25mL solvent absolute methanol, in temperature
Degree is to react 24 h under conditions of 45 ~ 65 DEG C, cooling, filters, and controls solvent volatilization crystallization, obtain yellow under conditions of 20 ~ 35 DEG C
Look transparent crystal, is 2-carbonyl-3-phenylpropionic acid to methoxybenzoyl hydrazone Dibenzyltin complex.Productivity：75.2%.Molten
Point：64~66℃(dec).
Elementary analysis (C64H64N4O10Sn2)：Calculated value：C 59.24, H 5.01, N 4.35；Measured value：C 59.23, H
5.03, N 4.37.
FT-IR (KBr, ν/cm-1): 3448, 3059, 3024, 2935, 2837, 1681, 1600, 1479,
1388, 1251, 1168, 1028, 844, 759, 698, 646, 590, 569, 522, 459.
1H NMR (500 MHz, CDCl3, δ/ppm): 8.00 (d,J= 8.8 Hz, 2H), 7.32 (m,
2H), 7.27 (m, 2H), 7.20-7.23 (m, 1H), 6.96 (d,J= 8.8 Hz, 2H), 6.83 (s,
10H), 3.91 (s, 3H), 3.88 (s, 2H), 3.48 (s, 3H), 3.17 (d,J= 11.6 Hz, 2H),
3.13 (d,J= 11.6 Hz, 2H).
13C NMR (126 MHz, CDCl3, δ/ppm): 174.74, 168.12, 162.92, 150.78,
136.28, 135.33, 130.85, 129.97, 128.44, 128.20, 128.11, 126.59, 125.49,
125.23, 113.50, 55.43, 50.82, 34.99, 32.17.
119Sn NMR (187 MHz, CDCl3, δ/ppm): -334.35.
Crystallographic data：Anorthic system, space group P-1, a=1.04461 (12) nm, b=1.17203 (14) nm,
C=1.30628 (15) nm, α=84.1900 (10) °, β=71.6100 (10) °, γ=72.6240 (10) °, Z=1, V=
1.4483(3) nm3, Dc=1.475 Mg m-3, m (MoK α)=0.925 mm-1, F (000)=656.
Embodiment 4：
The preparation to methoxybenzoyl hydrazone Dibenzyltin complex for the 2-carbonyl-3-phenylpropionic acid：
3.720g (10.0mmol) TriphenylphosphineoxComplex, 1.710g is added in the 500mL there-necked flask having nitrogen to protect
(10.3mmol) to methoxybenzoyl hydrazine, 1.650g (11.0mmol) benzoyl formic acid and 210mL solvent absolute methanol,
Temperature is to react 22 h under conditions of 45 ~ 65 DEG C, cooling, filters, and controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C,
Yellow transparent crystal, is 2-carbonyl-3-phenylpropionic acid to methoxybenzoyl hydrazone Dibenzyltin complex.Productivity：73.9%.
Fusing point：64~66℃(dec).
Elementary analysis (C64H64N4O10Sn2)：Calculated value：C 59.24, H 5.01, N 4.35；Measured value：C 59.23, H
5.03, N 4.37.
FT-IR (KBr, ν/cm-1): 3448, 3059, 3024, 2935, 2837, 1681, 1600, 1479,
1388, 1251, 1168, 1028, 844, 759, 698, 646, 590, 569, 522, 459.
1H NMR (500 MHz, CDCl3, δ/ppm): 8.00 (d,J= 8.8 Hz, 2H), 7.32 (m,
2H), 7.27 (m, 2H), 7.20-7.23 (m, 1H), 6.96 (d,J= 8.8 Hz, 2H), 6.83 (s,
10H), 3.91 (s, 3H), 3.88 (s, 2H), 3.48 (s, 3H), 3.17 (d,J= 11.6 Hz, 2H),
3.13 (d,J= 11.6 Hz, 2H).
13C NMR (126 MHz, CDCl3, δ/ppm): 174.74, 168.12, 162.92, 150.78,
136.28, 135.33, 130.85, 129.97, 128.44, 128.20, 128.11, 126.59, 125.49,
125.23, 113.50, 55.43, 50.82, 34.99, 32.17.
119Sn NMR (187 MHz, CDCl3, δ/ppm): -334.35.
Crystallographic data：Anorthic system, space group P-1, a=1.04461 (12) nm, b=1.17203 (14) nm,
C=1.30628 (15) nm, α=84.1900 (10) °, β=71.6100 (10) °, γ=72.6240 (10) °, Z=1, V=
1.4483(3) nm3, Dc=1.475 Mg m-3, m (MoK α)=0.925 mm-1, F (000)=656.
Test example：
Methoxybenzoyl hydrazone Dibenzyltin complex, its Anticancer Activity in vitro are surveyed by the 2-carbonyl-3-phenylpropionic acid of the present invention
Surely realized by MTT experiment method.
MTT analytic approach：
It with metabolism reduction 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide is
Basis.Succinate dehydrogenase in living cells mitochondria can make exogenous MTT be reduced to water-insoluble bluish violet crystallization first a ceremonial jade-ladle, used in libation
(Formazan) and be deposited in cell, and dead cell is without this function.Dimethyl sulfoxide (DMSO) (DMSO) can dissolve the first a ceremonial jade-ladle, used in libation in cell,
Measure the optical density of characteristic wavelength with ELIASA, can indirectly reflect living cells quantity.
Mtt assay is used to measure the 2-carbonyl-3-phenylpropionic acid of embodiment 1 preparation to methoxybenzoyl hydrazone Dibenzyltin
The inhibitory activity to human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) for the complex.
Cell line and cultivating system：H460, HepG2 and MCF7 cell line 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 liquid (1nM ~ 10 μM) is added separately in each hole according to the concentration 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), control 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 solution).After placing 4h at 37 DEG C, remove upper strata
Clear liquid.Every hole adds 150 μ L DMSO, vibrates 5min, makes Formazan crystallization dissolve.Finally, utilize automatic ELIASA 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, complex 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 approach
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-3-phenylpropionic acid is used as cancer therapy drug to methoxybenzoyl hydrazone Dibenzyltin complex, to human lung carcinoma cell (H460), people
HCC (HepG2) and human breast cancer cell (MCF7) have certain drug effect, can be as the candidate compound of cancer therapy drug.
Methoxybenzoyl hydrazone Dibenzyltin complex cancer therapy drug external activity is surveyed by table 1 2-carbonyl-3-phenylpropionic acid
Examination data.
| People's lung cancer | People's liver cancer | Human breast carcinoma | |
| Cell line | H460 | HepG2 | MCF7 |
| IC50(μM) | 6.66±0.65 | 5.64±0.49 | 6.12±0.58 |
2-carbonyl-3-phenylpropionic acid prepared by remaining embodiment to methoxybenzoyl hydrazone Dibenzyltin complex with MTT
The active anticancer method of testing to human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) for the method
Same 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
Within the scope of these modifications and modification belong to 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-3-phenylpropionic acid is to a methoxybenzoyl hydrazone Dibenzyltin complex, is joining of following structure formula (I)
Compound：
(I)
Wherein Ph is phenyl, and R is benzyl.
2. methoxybenzoyl hydrazone Dibenzyltin is coordinated by the one 2-carbonyl-3-phenylpropionic acid that contains as claimed in claim 1
Thing, its ir data：FT-IR (KBr, ν/cm-1): 3448, 3059, 3024, 2935, 2837, 1681,
1600, 1479, 1388, 1251, 1168, 1028, 844, 759, 698, 646, 590, 569, 522, 459；Its
Nuclear-magnetism modal data：1H NMR (500 MHz, CDCl3, δ/ppm): 8.00 (d,J= 8.8 Hz, 2H), 7.32 (m,
2H), 7.27 (m, 2H), 7.20-7.23 (m, 1H), 6.96 (d,J= 8.8 Hz, 2H), 6.83 (s,
10H), 3.91 (s, 3H), 3.88 (s, 2H), 3.48 (s, 3H), 3.17 (d,J= 11.6 Hz, 2H),
3.13 (d,J= 11.6 Hz, 2H)；13C NMR (126 MHz, CDCl3, δ/ppm): 174.74, 168.12,
162.92, 150.78, 136.28, 135.33, 130.85, 129.97, 128.44, 128.20, 128.11,
126.59, 125.49, 125.23, 113.50, 55.43, 50.82, 34.99, 32.17；119Sn NMR (187 MHz,
CDCl3, δ/ppm): -334.35.
3. 2-carbonyl-3-phenylpropionic acid as claimed in claim 1 is to methoxybenzoyl hydrazone Dibenzyltin complex, wherein,
Described 2-carbonyl-3-phenylpropionic acid is crystal structure to methoxybenzoyl hydrazone Dibenzyltin complex, its crystallographic data
As follows：Anorthic system, space group P-1, a=1.04461 (12) nm, b=1.17203 (14) nm, c=1.30628
(15) nm, α=84.1900 (10) °, β=71.6100 (10) °, γ=72.6240 (10) °, Z=1, V=1.4483 (3)
nm3, Dc=1.475 Mg m-3, m (MoK α)=0.925 mm-1, F (000)=656；In molecule, tin atom is seven coordination distortion
Pentagonal bipyramid configuration.
4. methoxybenzoyl hydrazone Dibenzyltin complex is had certain by 2-carbonyl-3-phenylpropionic acid described in claim 1
Thermally-stabilised scope, can stable existence below 64 DEG C.
5. the preparation side to methoxybenzoyl hydrazone Dibenzyltin complex for the 2-carbonyl-3-phenylpropionic acid described in claim 1
Method, is characterized in that adding TriphenylphosphineoxComplex in the reaction vessel having nitrogen to protect, to methoxybenzoyl hydrazine, benzoyl
Formic acid and solvent absolute methanol, react 5 ~ 24 h, cooling under conditions of temperature is 45 ~ 65 DEG C, filter, at the bar of 20 ~ 35 DEG C
Control solvent volatilization crystallization under part, obtain yellow transparent crystal, be 2-carbonyl-3-phenylpropionic acid to methoxybenzoyl hydrazone dibenzyl
Base tin complex.
6. the method for preparation as claimed in claim 5, it is characterised in that described TriphenylphosphineoxComplex, to methoxybenzene first
Hydrazides, the amount ratio of material of benzoyl formic acid three are 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
Benzyl stannous chloride adds 15 ~ and 35 milliliters.
8. 2-carbonyl-3-phenylpropionic acid described in claim 1 to methoxybenzoyl hydrazone Dibenzyltin complex prepare anticancer
Application in medicine.
9. the application described in claim 8, wherein said cancer cell is human lung carcinoma cell, human liver cancer cell, human breast cancer cell.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610747512.3A CN106432324A (en) | 2016-08-29 | 2016-08-29 | 2-carbonyl-3-phenylpropionic acid p-methoxybenzoyl hydrazone dibenzyl stannic complex as well as preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610747512.3A CN106432324A (en) | 2016-08-29 | 2016-08-29 | 2-carbonyl-3-phenylpropionic acid p-methoxybenzoyl hydrazone dibenzyl stannic complex as well as preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106432324A true CN106432324A (en) | 2017-02-22 |
Family
ID=58182776
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610747512.3A Pending CN106432324A (en) | 2016-08-29 | 2016-08-29 | 2-carbonyl-3-phenylpropionic acid p-methoxybenzoyl hydrazone dibenzyl stannic complex as well as preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106432324A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101503423A (en) * | 2008-11-17 | 2009-08-12 | 聊城大学 | Parachlorobenzoyl hydrazone organotin complex, preparation and use |
| CN105753896A (en) * | 2016-04-11 | 2016-07-13 | 衡阳师范学院 | 2-carbonyl-3-phenylpropionic acid p-hydroxyphenylcarbonylhydrazone dibenzyl tin complex as well as preparation method and application thereof |
| CN105777799A (en) * | 2016-04-22 | 2016-07-20 | 衡阳师范学院 | 2-carbonyl-3-phenylpropionic acid benzoyl hydrazone dibenzyl tin complex as well as preparation method and application thereof |
| CN105859768A (en) * | 2016-04-23 | 2016-08-17 | 衡阳师范学院 | 2-carbonyl-3-phenylpropionic acid salicylhydrazone dibenzyltin complex and preparation method and application thereof |
-
2016
- 2016-08-29 CN CN201610747512.3A patent/CN106432324A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101503423A (en) * | 2008-11-17 | 2009-08-12 | 聊城大学 | Parachlorobenzoyl hydrazone organotin complex, preparation and use |
| CN105753896A (en) * | 2016-04-11 | 2016-07-13 | 衡阳师范学院 | 2-carbonyl-3-phenylpropionic acid p-hydroxyphenylcarbonylhydrazone dibenzyl tin complex as well as preparation method and application thereof |
| CN105777799A (en) * | 2016-04-22 | 2016-07-20 | 衡阳师范学院 | 2-carbonyl-3-phenylpropionic acid benzoyl hydrazone dibenzyl tin complex as well as preparation method and application thereof |
| CN105859768A (en) * | 2016-04-23 | 2016-08-17 | 衡阳师范学院 | 2-carbonyl-3-phenylpropionic acid salicylhydrazone dibenzyltin complex and preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| MIN HONG等: "Weakly-bridged dimeric diorganotin(IV) compounds derived from pyruvic acid hydrazone Schiff base ligands: Synthesis, characterization and crystal structures", 《SOLID STATE SCIENCES》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106432323A (en) | 2-carbonyl butyric acid p-methoxy benzoyl hydrazone di-n-butyltin complex and preparation method and application thereof | |
| CN106366113A (en) | 2-oxo-propionic acid p-toluyl hydrazone di-2, 4-dichlorobenzyltin complex and its preparation method and use | |
| CN106336427A (en) | 2-carbonyl-2-phenyl acetic acid p-nitrobenzoylhydrazone bis(2,4-dichlorobenzyl)tin complex and preparation method and application thereof | |
| CN106220669B (en) | A kind of dialkyl tin complex of the ligand containing acylhydrazone and its preparation method and application | |
| CN106366118B (en) | A kind of 2- carbonyl -2- phenylacetic acid is to tert-butyl benzoyl hydrazone stannous phenide complex and its preparation method and application | |
| CN106336430A (en) | 2-oxo-butyric acid p-methyl benzoyl hydrazone di-n-butyl tin complex and preparation method and application thereof | |
| CN106432322A (en) | 2-Carbonyl-2-phenylacetic acid p-nitrobenzoyl hydrazone diphenyltin complex, and preparation method and application thereof | |
| CN106380480B (en) | A kind of ALPHA-ketobutyric acid p-nitrophenyl formyl hydrazone stannous phenide complex and its preparation method and application | |
| CN106432324A (en) | 2-carbonyl-3-phenylpropionic acid p-methoxybenzoyl hydrazone dibenzyl stannic complex as well as preparation method and application thereof | |
| CN106220674B (en) | A kind of Dibenzyltin complex and its preparation method and application | |
| CN106366120B (en) | A kind of ALPHA-ketobutyric acid is to methoxybenzoyl hydrazone stannous phenide complex and its preparation method and application | |
| CN106366119B (en) | A kind of 2- carbonyls -2- phenylacetic acids are to methoxybenzoyl hydrazone di-n-butyl tin complex and its preparation method and application | |
| CN106336429B (en) | A kind of ALPHA-ketobutyric acid is to toluyl hydrazone stannous phenide complex and its preparation method and application | |
| CN106336428A (en) | 2-carbonyl-2-phenyl acetic acid p-nitro benzoyl hydrazone dibenzyl tin complex and preparation method and application thereof | |
| CN106220673A (en) | A kind of 2 carbonyl 2 phenylacetic acids are to toluyl hydrazone di-n-butyl tin coordination compound and its preparation method and application | |
| CN106349280A (en) | 2-carbonyl-2-phenyl acetic acid p-methoxy-benzoyl hydrazone diphenyltin complex and preparing method and application thereof | |
| CN106317105A (en) | 2- carbonyl- 2- phenyl acetic acid p-nitro benzoyl hydrazone 2-n-butyl tin complex and preparing method and application thereof | |
| CN106336432A (en) | 2-oxo-propionic acid p-methoxyl benzoyl hydrazone diphenyl tin complex and preparation method and application thereof | |
| CN106220676A (en) | A kind of 2 carbonyl propionic acids are to methoxybenzoyl hydrazone Dibenzyltin coordination compound and its preparation method and application | |
| CN106220671A (en) | A kind of 2 carbonyl 2 phenylacetic acids are to toluyl hydrazone stannous phenide coordination compound and its preparation method and application | |
| CN106243148A (en) | A kind of 2 carbonyl 2 phenylacetic acid benzoyl hydrazone stannous phenide coordination compounds and its preparation method and application | |
| CN106279250A (en) | A kind of 2 carbonyl 3 phenylpropionic acid para hydroxybenzene formyl hydrazone stannous phenide coordination compounds and its preparation method and application | |
| CN106317104A (en) | 2- carbonyl propionic acid p-tert-butyl benzoyl hydrazone stannous phenide complex and preparing method and application thereof | |
| CN106366117A (en) | 2-carbonyl-3-phenylpropionic-p-tert-butyl benzoyl hydrazone dibenzyl tin complex, and preparation method and application thereof | |
| CN106220672A (en) | A kind of 2 carbonyl 2 phenylacetic acids are to tert-butyl benzoyl hydrazone di-n-butyl tin coordination compound and its preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170222 |