CN106279262A - A kind of 2 carbonyl 3 phenylpropionic acids are to toluyl hydrazone two (2,4 dichloro benzyl) stannum coordination compound and its preparation method and application - Google Patents
A kind of 2 carbonyl 3 phenylpropionic acids are to toluyl hydrazone two (2,4 dichloro benzyl) stannum coordination compound and its preparation method and application Download PDFInfo
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- CN106279262A CN106279262A CN201610699707.5A CN201610699707A CN106279262A CN 106279262 A CN106279262 A CN 106279262A CN 201610699707 A CN201610699707 A CN 201610699707A CN 106279262 A CN106279262 A CN 106279262A
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- carbonyl
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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 3 phenylpropionic acids to toluyl hydrazone two (2,4 dichloro benzyl) stannum coordination compound, for the coordination compound of following structure formula (I), wherein Ph is phenyl, and R is 2,4 dichloro benzyls.The invention also discloses this 2 carbonyl 3 phenylpropionic acid to the preparation method of toluyl hydrazone two (2,4 dichloro benzyl) stannum coordination compound and the application in preparing cancer therapy drug.
Description
Technical field
The present invention relates to a kind of 2-carbonyl-3-phenylpropionic acid to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound
And preparation method thereof, and toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound exists by this 2-carbonyl-3-phenylpropionic acid
Prepare the application in cancer therapy drug.
Background technology
Organotin is the metallo-organic compound that a class contains Sn-C key.Researcher just noticed before very early
The Anticancer Activity in vitro of organo-tin compound.The research of organotin (IV) antitumor activity of compound can trace back to nineteen twenty-nine.
1967, Kanisawa etc. thought that stannic chloride is invalid to the primary tumor of mice and rat.But in 1972, Brown found,
By food or drug administration by injection, triphenyltin acetate Ph3SnOOCCH3Can suppress the tumor growth of mice, and triphenyltin chloride
Then can not.Between 1972 ~ 1977 years, Holland's substantial amounts of organo-tin compound of scholar's research, but find no further screening valency
The compound of value.They continue deeper into research, finally found that the tin compound of two organic group coordinations, such as tin-oxide
(R2SnO), stannum hydroxide ［ SnR2(OH) X ］ etc. have an anti-tumor activity, and find out that they all contain or hydrolyze and can produce stannum oxygen
Key.1980, Crowe etc. was found that again some organo-tin compounds have preferable active anticancer, from this, resisted about organotin
The research of cancer activity becomes another extremely active focus after cisplatin.1989, American National anticancer research institute
(National Cancer Institute) has carried out antitumor activity screening, result table to more than 2,000 kinds of organo-tin compounds
Brighter organo-tin compounds have inhibitory action to P388 Lymphocytic leukemia.2002, Gielen et al. was to organic
The activity of stannum carboxylate compound has done comprehensive summing up, thinks that many organo-tin compounds have the most external really after research
Active anticancer.
Research shows, the organic group that organotin atom connects and the part participating in coordination decide organo-tin compound
Biological activity, select some itself have good biological activity organic ligand with in organotin tin atom coordination cause
The great interest of people.Acylhydrazone is by a class Schiff compound of hydrazide kind compound modification, they
It is condensed by aldehydes or ketones and hydrazides and forms, molecule has the of bonding similar with peptide bond, there is good biological activity, stronger joining
Capability and various coordination mode, and have a wide range of applications at aspects such as medicine, pesticide, material and analytical reagents.Closely
Nian Lai, it is compared in terms of biological activity by the most many research worker in depth studies, and research finds acylhydrazone class
Compound has the various active such as anticancer, sterilization, antiinflammatory.Therefore, acylhydrazone class Schiff part is combined with organotin, it is intended to
Obtain the noval chemical compound that biological activity is higher, become the research direction that people are interested.
Chinese patent CN 102718794A discloses a kind of double acylhydrazone class Schiff stannous phenide coordination compound and in system
Standby Antilung gland cancer, colon cancer, leukaemia medicine in application.
Chinese patent CN 101851251A disclose a kind of acylhydrazone class Schiff part dibutyl tin coordination compound and
Application in preparation treatment hepatocarcinoma, adenocarcinoma of lung, breast carcinoma, carcinoma of prostate, colon cancer or the youngest leukemic medicine of grain.
Document (Journal of Organometallic Chemistry, 2014,75:83-91) is reported, organotin
Acylhydrazone class Schiff base complex is thin to human colon cancer cell (HCT-116), human lung adenocarcinoma cell (A549), human umblilical vein endothelial
Born of the same parents (HUVEC) have relatively strong biological activity, and are better than carboplatin.
Document (Journal of Organometallic Chemistry, 2013,724:23-31) is reported, series has
Machine stannum acylhydrazone class Schiff base complex, organo-tin compound and acylhydrazone class Schiff part are respectively to human lung adenocarcinoma cell
(A549), the inhibitory action of the cancerous cell such as human colon cancer cell (HCT-8), people in loop (hl-60).
Document (Bioorganic & Medicinal Chemistry Letters, 2015,25:4461-4463)
Report, multiple acylhydrazone class Schiff part is to human liver cancer cell (HuH-7) and the active anticancer of human lung adenocarcinoma cell (A549).
Document (Journal of Organometallic Chemistry, 2016,804:48-58) is reported, two hydrocarbon
Base stannum acylhydrazone class Schiff base complex is to human lung adenocarcinoma cell (A549), human cervical carcinoma cell (HeLa), human breast cancer cell
(MCF-7) inhibitory action of cancerous cell such as.
Being the material that the experiment proved that and have active anticancer based on acylhydrazone class Schiff organotin complex, the present invention selects
Select and toluyl hydrazine, Sodium.beta.-phenylpyruvate and two (2,4-dichloro benzyl) stannum dichloride are reacted under certain condition, synthesize
To human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) are had certain inhibitory activity
Coordination compound, for exploitation cancer therapy drug provide new approach.
Summary of the invention
The first object of the present invention there is provided a kind of 2-carbonyl-3-phenylpropionic acid to toluyl hydrazone two (2,4-bis-
Chlorobenzyl) stannum coordination compound.
The second object of the present invention is to provide above-mentioned 2-carbonyl-3-phenylpropionic acid to toluyl hydrazone two (2,4-dichloro
Benzyl) stannum coordination compound preparation method.
The third object of the present invention is to provide above-mentioned 2-carbonyl-3-phenylpropionic acid to toluyl hydrazone two (2,4-dichloro
Benzyl) application in preparing cancer therapy drug of the stannum coordination compound.
As a kind of 2-carbonyl-3-phenylpropionic acid of a first aspect of the present invention to toluyl hydrazone two (2,4-dichloro
Benzyl) stannum coordination compound, for the coordination compound of structure formula (I)
(I)
Wherein Ph is phenyl, and R is 2,4-dichloro benzyl.
2-carbonyl-3-the phenylpropionic acid of the present invention to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound through element
Analysis, infrared spectrum, nuclear magnetic resoance spectrum and X-ray single crystal diffraction structural analysis, result is as follows:
Elementary analysis (C62H48Cl8N4O6Sn2): value of calculation: C 50.79, H 3.30, N 3.82；Measured value: C 50.70, H
3.31, N 3.84.
FT-IR (KBr, ν/cm-1): 3091, 3059, 3030, 2951, 1680, 1612, 1579, 1473,
1392, 1311, 1274, 1203, 1176, 1111, 1074, 842, 746, 725, 653, 636, 592, 567,
514, 476, 447。
1H NMR (500 MHz, CDCl3, δ/ppm): 7.85 (d, J =8.1 Hz, 2H), 7.47 (m, 2H),
7.28~7.32 (m, 3H), 7.25 (s, 2H), 7.13 (s, 2H), 6.92 (m, 4H), 4.29 (s, 2H),
3.11 (d, J =12.0 Hz, 2H), 3.04 (d, J =12.0 Hz, 2H), 3.45 (s, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.80, 163.20, 154.75, 143.59,
134.40, 133.28, 132.68, 132.16, 130.67, 130.11, 129.14, 129.10, 128.86,
128.71, 128.58, 127.36, 123.16, 32.80, 29.71, 27.42, 21.81。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -239.13。
2-carbonyl-3-the phenylpropionic acid of the present invention is crystal to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound
Structure, its crystal is anorthic system, space group P-1, a=1.0058 (3) nm, b=1.0356 (3) nm, c=1.5771
(5) nm, α=98.856 (4) °, β=102.169 (4) °, γ=105.332 (4) °, Z=1, V=1.5099 (8) nm3,
Dc= 1.612 Mg·m-3, m (MoK α)=1.236 mm-1, F (000)=732.
2-carbonyl-3-the phenylpropionic acid of the present invention structure to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound
Feature is: in molecule, tin atom is hexa-coordinate distorted octahedron configuration.
2-carbonyl-3-the phenylpropionic acid of the present invention has one to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound
Fixed thermally-stabilised scope, can stable existence below 220 DEG C.
As a kind of 2-carbonyl-3-phenylpropionic acid of a second aspect of the present invention to toluyl hydrazone two (2,4-dichloro
Benzyl) preparation method of stannum coordination compound, add in the reaction vessel having nitrogen to protect two (2,4-dichloro benzyl) stannum dichloride,
To toluyl hydrazine, Sodium.beta.-phenylpyruvate and solvent absolute methanol, under conditions of temperature is 45 ~ 65 DEG C, react 5 ~ 24 h, cold
But, filter, under conditions of 20 ~ 35 DEG C, control solvent volatilization crystallization, obtain yellow transparent crystal, be 2-carbonyl-3-phenyl third
Acid is to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound.
The preparation to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound of the 2-carbonyl-3-phenylpropionic acid of the present invention
Feature is: from the relatively easy raw material being easy to get, without the separation of intermediate, directly obtains baroque molecule, i.e. one
Pot method；On such reaction economically and environmentally close friend advantageously.
In a preferred embodiment of the invention, described two (2,4-dichloro benzyl) stannum dichloride, to toluyl
Hydrazine, Sodium.beta.-phenylpyruvate three the amount of material than for 1:(1 ~ 1.05): (1.05 ~ 1.15).
In a preferred embodiment of the invention, described solvent absolute methanol consumption is every mM two (2,4-dichloros
Benzyl) stannum dichloride adds 15 ~ and 35 milliliters.
As a kind of 2-carbonyl-3-phenylpropionic acid of a third aspect of the present invention to toluyl hydrazone two (2,4-dichloro
Benzyl) application in preparing cancer therapy drug of the stannum coordination compound.
Toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound is entered by applicant by above-mentioned 2-carbonyl-3-phenylpropionic acid
Anticancer Activity in vitro of having gone determines research, it is thus identified that 2-carbonyl-3-phenylpropionic acid is to toluyl hydrazone two (2,4-benzyl dichlorides
Base) stannum coordination compound has certain anticancer bioactive, say, that and the purposes of above-mentioned coordination compound is in preparing cancer therapy drug
Application, be exactly the application in preparing anti-human pulmonary carcinoma, people's hepatocarcinoma and human breast carcinoma medicine specifically.
2-carbonyl-3-the phenylpropionic acid of the present invention to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound to people's lung
Cancerous cell, human liver cancer cell and human breast cancer cell demonstrate good active anticancer, the 2-carbonyl-3-phenylpropionic acid of the present invention
To features such as toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound active anticancer height, low cost, preparation method are simple, for
Develop new cancer therapy drug and provide new way.
Accompanying drawing explanation
Fig. 1 is the 2-carbonyl-3-phenylpropionic acid IR spectrogram to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound.
Fig. 2 is that 2-carbonyl-3-phenylpropionic acid is to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound1H NMR
Spectrogram.
Fig. 3 is that 2-carbonyl-3-phenylpropionic acid is to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound13C NMR
Spectrogram.
Fig. 4 is that 2-carbonyl-3-phenylpropionic acid is to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound119Sn
NMR spectra.
Fig. 5 is that the crystal of toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound is tied by 2-carbonyl-3-phenylpropionic acid
Composition.
Fig. 6 is the 2-carbonyl-3-phenylpropionic acid TG-DTG to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound
Curve.
Detailed description of the invention
By detailed description below, the present invention is described in further detail.
Embodiment 1:
The preparation to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound of the 2-carbonyl-3-phenylpropionic acid:
0.510g (1.0mmol) two (2,4-dichloro benzyl) dichloride is added in the 100mL there-necked flask having nitrogen to protect
Stannum, 0.150g (1.0mmol) to toluyl hydrazine, 0.205g (1.1mmol) Sodium.beta.-phenylpyruvate and 15mL solvent without water beetle
Alcohol, reacts 8 h under conditions of temperature is 45 ~ 65 DEG C, cooling, filters, and controls solvent volatilization knot under conditions of 20 ~ 35 DEG C
Crystalline substance, obtains yellow transparent crystal, is 2-carbonyl-3-phenylpropionic acid and coordinates toluyl hydrazone two (2,4-dichloro benzyl) stannum
Thing.Productivity: 65.5%.Fusing point: 220 ~ 222 DEG C (dec).
Elementary analysis (C62H48Cl8N4O6Sn2): value of calculation: C 50.79, H 3.30, N 3.82；Measured value: C 50.70, H
3.31, N 3.84.
FT-IR (KBr, ν/cm-1): 3091, 3059, 3030, 2951, 1680, 1612, 1579, 1473,
1392, 1311, 1274, 1203, 1176, 1111, 1074, 842, 746, 725, 653, 636, 592, 567,
514, 476, 447。
1H NMR (500 MHz, CDCl3, δ/ppm): 7.85 (d, J =8.1 Hz, 2H), 7.47 (m, 2H),
7.28~7.32 (m, 3H), 7.25 (s, 2H), 7.13 (s, 2H), 6.92 (m, 4H), 4.29 (s, 2H),
3.11 (d, J =12.0 Hz, 2H), 3.04 (d, J =12.0 Hz, 2H), 3.45 (s, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.80, 163.20, 154.75, 143.59,
134.40, 133.28, 132.68, 132.16, 130.67, 130.11, 129.14, 129.10, 128.86,
128.71, 128.58, 127.36, 123.16, 32.80, 29.71, 27.42, 21.81。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -239.13。
Crystallographic data: anorthic system, space group P-1, a=1.0058 (3) nm, b=1.0356 (3) nm, c=
1.5771 (5) nm, α=98.856 (4) °, β=102.169 (4) °, γ=105.332 (4) °, Z=1, V=1.5099 (8)
nm3, Dc=1.612 Mg m-3, m (MoK α)=1.236 mm-1, F (000)=732.
Embodiment 2:
The preparation to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound of the 2-carbonyl-3-phenylpropionic acid:
0.510g (1.0mmol) two (2,4-dichloro benzyl) dichloride is added in the 100mL there-necked flask having nitrogen to protect
Stannum, 0.150g (1.0mmol) to toluyl hydrazine, 0.195g (1.05mmol) Sodium.beta.-phenylpyruvate and 35mL solvent without water beetle
Alcohol, reacts 5 h under conditions of temperature is 45 ~ 65 DEG C, cooling, filters, and controls solvent volatilization knot under conditions of 20 ~ 35 DEG C
Crystalline substance, obtains yellow transparent crystal, is 2-carbonyl-3-phenylpropionic acid and coordinates toluyl hydrazone two (2,4-dichloro benzyl) stannum
Thing.Productivity: 68.5%.Fusing point: 220 ~ 222 DEG C (dec).
Elementary analysis (C62H48Cl8N4O6Sn2): value of calculation: C 50.79, H 3.30, N 3.82；Measured value: C 50.70, H
3.31, N 3.84.
FT-IR (KBr, ν/cm-1): 3091, 3059, 3030, 2951, 1680, 1612, 1579, 1473,
1392, 1311, 1274, 1203, 1176, 1111, 1074, 842, 746, 725, 653, 636, 592, 567,
514, 476, 447。
1H NMR (500 MHz, CDCl3, δ/ppm): 7.85 (d, J =8.1 Hz, 2H), 7.47 (m, 2H),
7.28~7.32 (m, 3H), 7.25 (s, 2H), 7.13 (s, 2H), 6.92 (m, 4H), 4.29 (s, 2H),
3.11 (d, J =12.0 Hz, 2H), 3.04 (d, J =12.0 Hz, 2H), 3.45 (s, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.80, 163.20, 154.75, 143.59,
134.40, 133.28, 132.68, 132.16, 130.67, 130.11, 129.14, 129.10, 128.86,
128.71, 128.58, 127.36, 123.16, 32.80, 29.71, 27.42, 21.81。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -239.13。
Crystallographic data: anorthic system, space group P-1, a=1.0058 (3) nm, b=1.0356 (3) nm, c=
1.5771 (5) nm, α=98.856 (4) °, β=102.169 (4) °, γ=105.332 (4) °, Z=1, V=1.5099 (8)
nm3, Dc=1.612 Mg m-3, m (MoK α)=1.236 mm-1, F (000)=732.
Embodiment 3:
The preparation to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound of the 2-carbonyl-3-phenylpropionic acid:
0.510g (1.0mmol) two (2,4-dichloro benzyl) dichloride is added in the 100mL there-necked flask having nitrogen to protect
Stannum, 0.158g (1.05mmol) are anhydrous to toluyl hydrazine, 0.214g (1.15mmol) Sodium.beta.-phenylpyruvate and 25mL solvent
Methanol, reacts 24 h under conditions of temperature is 45 ~ 65 DEG C, cooling, filters, and controls solvent volatilization under conditions of 20 ~ 35 DEG C
Crystallization, obtains yellow transparent crystal, is 2-carbonyl-3-phenylpropionic acid and coordinates toluyl hydrazone two (2,4-dichloro benzyl) stannum
Thing.Productivity: 68.1%.Fusing point: 220 ~ 222 DEG C (dec).
Elementary analysis (C62H48Cl8N4O6Sn2): value of calculation: C 50.79, H 3.30, N 3.82；Measured value: C 50.70, H
3.31, N 3.84.
FT-IR (KBr, ν/cm-1): 3091, 3059, 3030, 2951, 1680, 1612, 1579, 1473,
1392, 1311, 1274, 1203, 1176, 1111, 1074, 842, 746, 725, 653, 636, 592, 567,
514, 476, 447。
1H NMR (500 MHz, CDCl3, δ/ppm): 7.85 (d, J =8.1 Hz, 2H), 7.47 (m, 2H),
7.28~7.32 (m, 3H), 7.25 (s, 2H), 7.13 (s, 2H), 6.92 (m, 4H), 4.29 (s, 2H),
3.11 (d, J =12.0 Hz, 2H), 3.04 (d, J =12.0 Hz, 2H), 3.45 (s, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.80, 163.20, 154.75, 143.59,
134.40, 133.28, 132.68, 132.16, 130.67, 130.11, 129.14, 129.10, 128.86,
128.71, 128.58, 127.36, 123.16, 32.80, 29.71, 27.42, 21.81。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -239.13。
Crystallographic data: anorthic system, space group P-1, a=1.0058 (3) nm, b=1.0356 (3) nm, c=
1.5771 (5) nm, α=98.856 (4) °, β=102.169 (4) °, γ=105.332 (4) °, Z=1, V=1.5099 (8)
nm3, Dc=1.612 Mg m-3, m (MoK α)=1.236 mm-1, F (000)=732.
Embodiment 4:
The preparation to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound of the 2-carbonyl-3-phenylpropionic acid:
5.100g (10.0mmol) two (2,4-dichloro benzyl) dichloride is added in the 500mL there-necked flask having nitrogen to protect
Stannum, 1.545g (10.3mmol) are anhydrous to toluyl hydrazine, 2.046g (11.0mmol) Sodium.beta.-phenylpyruvate and 200mL solvent
Methanol, reacts 22 h under conditions of temperature is 45 ~ 65 DEG C, cooling, filters, and controls solvent volatilization under conditions of 20 ~ 35 DEG C
Crystallization, obtains yellow transparent crystal, is 2-carbonyl-3-phenylpropionic acid and coordinates toluyl hydrazone two (2,4-dichloro benzyl) stannum
Thing.Productivity: 63.7%.Fusing point: 220 ~ 222 DEG C (dec).
Elementary analysis (C62H48Cl8N4O6Sn2): value of calculation: C 50.79, H 3.30, N 3.82；Measured value: C 50.70, H
3.31, N 3.84.
FT-IR (KBr, ν/cm-1): 3091, 3059, 3030, 2951, 1680, 1612, 1579, 1473,
1392, 1311, 1274, 1203, 1176, 1111, 1074, 842, 746, 725, 653, 636, 592, 567,
514, 476, 447。
1H NMR (500 MHz, CDCl3, δ/ppm): 7.85 (d, J =8.1 Hz, 2H), 7.47 (m, 2H),
7.28~7.32 (m, 3H), 7.25 (s, 2H), 7.13 (s, 2H), 6.92 (m, 4H), 4.29 (s, 2H),
3.11 (d, J =12.0 Hz, 2H), 3.04 (d, J =12.0 Hz, 2H), 3.45 (s, 3H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 174.80, 163.20, 154.75, 143.59,
134.40, 133.28, 132.68, 132.16, 130.67, 130.11, 129.14, 129.10, 128.86,
128.71, 128.58, 127.36, 123.16, 32.80, 29.71, 27.42, 21.81。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -239.13。
Crystallographic data: anorthic system, space group P-1, a=1.0058 (3) nm, b=1.0356 (3) nm, c=
1.5771 (5) nm, α=98.856 (4) °, β=102.169 (4) °, γ=105.332 (4) °, Z=1, V=1.5099 (8)
nm3, Dc=1.612 Mg m-3, m (MoK α)=1.236 mm-1, F (000)=732.
Test example:
2-carbonyl-3-the phenylpropionic acid of the present invention is to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound, its In Vitro Anti
Cancer determination of activity is 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.
Mtt assay is used to measure the 2-carbonyl-3-phenylpropionic acid of embodiment 1 preparation to toluyl hydrazone two (2,4-bis-
Chlorobenzyl) stannum coordination compound is to human lung carcinoma cell (H460), human liver cancer cell (HepG2) and the suppression of human breast cancer cell (MCF7)
Activity.
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-3-phenylpropionic acid is used as cancer therapy drug to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound, to human lung carcinoma cell
(H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) there is certain drug effect, can be as the time of cancer therapy drug
Select compound.
Table 1 2-carbonyl-3-phenylpropionic acid is to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound anticarcinogen object
Outer active testing data.
| People's pulmonary carcinoma | People's hepatocarcinoma | Human breast carcinoma | |
| Cell strain | H460 | HepG2 | MCF7 |
| IC50(μM) | 8.34±0.38 | 4.09±0.58 | 4.54±0.20 |
Toluyl hydrazone two (2,4-dichloro benzyl) stannum is coordinated by 2-carbonyl-3-phenylpropionic acid prepared by remaining embodiment
The active anticancer of human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) is surveyed by thing with mtt assay
The same test example of method for testing, 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. a 2-carbonyl-3-phenylpropionic acid is to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound, for following structure
The coordination compound of formula (I):
(I)
Wherein Ph is phenyl, and R is 2,4-dichloro benzyl.
2. the one 2-carbonyl-3-phenylpropionic acid that contains as claimed in claim 1 is to toluyl hydrazone two (2,4-benzyl dichloride
Base) stannum coordination compound, its ir data: FT-IR (KBr, ν/cm-1): 3091, 3059, 3030, 2951, 1680,
1612, 1579, 1473, 1392, 1311, 1274, 1203, 1176, 1111, 1074, 842, 746, 725,
653, 636, 592, 567, 514, 476, 447；Its nuclear-magnetism modal data:1H NMR (500 MHz, CDCl3, δ/ppm):
7.85 (d, J =8.1 Hz, 2H), 7.47 (m, 2H), 7.28~7.32 (m, 3H), 7.25 (s, 2H), 7.13
(s, 2H), 6.92 (m, 4H), 4.29 (s, 2H), 3.11 (d, J =12.0 Hz, 2H), 3.04 (d, J =
12.0 Hz, 2H), 3.45 (s, 3H)；13C NMR (126 MHz, CDCl3, δ/ppm): 174.80, 163.20,
154.75, 143.59, 134.40, 133.28, 132.68, 132.16, 130.67, 130.11, 129.14,
129.10, 128.86, 128.71, 128.58, 127.36, 123.16, 32.80, 29.71, 27.42, 21.81；119Sn NMR (187 MHz, CDCl3, δ/ppm): -239.13。
3. toluyl hydrazone two (2,4-dichloro benzyl) stannum is coordinated by 2-carbonyl-3-phenylpropionic acid as claimed in claim 1
Thing, wherein, described 2-carbonyl-3-phenylpropionic acid is crystal knot to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound
Structure, its crystallographic data is as follows: anorthic system, space group P-1, a=1.0058 (3) nm, b=1.0356 (3) nm, c=
1.5771 (5) nm, α=98.856 (4) °, β=102.169 (4) °, γ=105.332 (4) °, Z=1, V=1.5099 (8)
nm3, Dc=1.612 Mg m-3, m (MoK α)=1.236 mm-1, F (000)=732；In molecule, tin atom is hexa-coordinate distortion
Octoploids structure.
4. toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound is had by 2-carbonyl-3-phenylpropionic acid described in claim 1
There is certain thermally-stabilised scope, can stable existence below 220 DEG C.
5. the 2-carbonyl-3-phenylpropionic acid described in claim 1 is to toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound
Preparation method, it is characterized in that in the reaction vessel having nitrogen to protect add two (2,4-dichloro benzyl) stannum dichloride, to first
Base benzoyl hydrazine, Sodium.beta.-phenylpyruvate and solvent absolute methanol, react 5 ~ 24 h, cooling, mistake under conditions of temperature is 45 ~ 65 DEG C
Filter, controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains yellow transparent crystal, be 2-carbonyl-3-phenylpropionic acid to first
Base benzoyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound.
6. the method for preparation as claimed in claim 5, it is characterised in that described two (2,4-dichloro benzyl) stannum dichloride, right
Toluyl hydrazine, Sodium.beta.-phenylpyruvate 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 absolute methanol consumption is every mM two
(2,4-dichloro benzyl) stannum dichloride adds 15 ~ and 35 milliliters.
8. toluyl hydrazone two (2,4-dichloro benzyl) stannum coordination compound is existed by 2-carbonyl-3-phenylpropionic acid described in claim 1
Prepare the application in cancer therapy drug.
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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