CN106336427B - A kind of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin complex and its preparation method and application - Google Patents

A kind of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin complex and its preparation method and application Download PDF

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CN106336427B
CN106336427B CN201610717177.2A CN201610717177A CN106336427B CN 106336427 B CN106336427 B CN 106336427B CN 201610717177 A CN201610717177 A CN 201610717177A CN 106336427 B CN106336427 B CN 106336427B
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dichloro benzyl
carbonyl
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tin
phenylacetic acid
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CN106336427A (en
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蒋伍玖
谭宇星
朱小明
邝代治
张复兴
冯泳兰
庾江喜
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Hengyang Normal University
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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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Abstract

The invention discloses a kind of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin complexs, are the complex of following structure formula (I), wherein Ph is phenyl, R 2,4- dichloro benzyl.The invention also discloses the preparation method of two (2,4- dichloro benzyl) the tin complex of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone and preparing the application in anticancer drug.

Description

A kind of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) Tin complex and its preparation method and application
Technical field
The present invention relates to a kind of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin complexs And preparation method thereof and two (2,4- dichloro benzyl) the tin complex of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone exist Prepare the application in anticancer drug.
Background technique
Organotin is a kind of metallo-organic compound containing Sn-C key.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 be traced 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 was 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 anti-tumor activity, and find out that they all contain or hydrolyze and can generate tin oxygen Key.1980, Crowe etc. had found that some organo-tin compounds have preferable anticancer activity 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 Bright some organo-tin compounds have inhibiting effect to P388 lymphocytic leukemia.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 Anticancer activity.
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 it is some itself with the active organic ligand of good biological in organotin tin atoms be coordinated causes The great interest of people.Acylhydrazone is one kind Schiff compound made of being modified as 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 multiplicity coordination mode, and medicine, pesticide, material and in terms of have a wide range of applications.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, by acylhydrazone class Schiff ligand in conjunction 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 discloses a kind of double acylhydrazone class Schiff stannous phenide complexs and its is 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 of preparation treatment liver cancer, adenocarcinoma of lung, breast cancer, prostate cancer, colon cancer or early young grain leukaemia.
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) report, series have 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, anticancer activity 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, 2016,804:48-58) 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) inhibiting effect of cancer cells such as.
It is the experiment proved that the substance with anticancer activity, present invention choosing based on acylhydrazone class Schiff organotin complex P-nitrobenzoylhydrazide, benzoyl formic acid and two (2,4- dichloro benzyl) stannous chloride are selected to react, synthesize under certain condition Having arrived has certain inhibitory activity to human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) Complex, for exploitation anticancer drug provide new approach.
Summary of the invention
There is provided a kind of two (2,4- bis- of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone for the first object of the present invention Chlorobenzyl) tin complex.
The second object of the present invention is to provide above-mentioned two (2,4- dichloro of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone Benzyl) tin complex preparation method.
The third object of the present invention is to provide above-mentioned two (2,4- dichloro of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone Benzyl) tin complex preparing the application in anticancer drug.
A kind of two (2,4- dichloro of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone as the first aspect of the present invention Benzyl) tin complex is the complex of structure formula (I)
(I)
Wherein Ph is phenyl, R 2,4- dichloro benzyl.
Two (2,4- dichloro benzyl) tin complex of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone of the invention is through element Analysis, infrared spectroscopy, nuclear magnetic resoance spectrum and X-ray single crystal diffraction structural analysis, as a result as follows:
Elemental analysis (C30H23Cl4N3O6Sn): calculated value: C 46.07, H 2.96, N 5.37；Measured value: C 46.11, H 2.96, N 5.38.
FT-IR (KBr, ν/cm-1): 3597, 3057, 2943, 2833, 1622, 1579, 1525, 1496, 1469, 1384, 1344, 1317, 1290, 1255, 1172, 1085, 850, 819, 719, 690, 655, 632, 592, 540, 514, 443, 406。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.19-8.22 (m, 2H), 7.85-7.88 (m, 4H), 7.55-7.60 (m, 3H), 7.19 (d, J = 2.1Hz, 2H), 7.10 (d, J = 8.4Hz, 2H), 6.93- 6.95 (dd, J 1 = 8.4Hz, J 2 = 2.1Hz, 2H), 3.50 (s, 3H), 3.43 (d, J = 12.2Hz, 2H), 3.33 (d, J = 12.2Hz, 2H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 173.09, 163.42, 151.63, 150.02, 137.82, 133.40, 133.11, 132.39, 132.11, 131.72, 131.27, 129.35, 128.85, 128.16, 127.91, 127.33, 123.37, 50.90, 30.11。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -279.92。
Two (2,4- dichloro benzyl) tin complex of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone of the invention is crystal Structure, crystal are as follows: monoclinic system, space group P2 (1)/c, a=1.15807 (7) nm, b=1.02876 (6) nm, c= 2.74978 (16) nm, α=γ=90 °, β=98.3990 (10) °, Z=2, V=3.2409 (3) nm3, Dc=1.603 Mg·m-3, m (MoK α)=1.165 mm-1, F (000)=1560.
The structure of two (2,4- dichloro benzyl) tin complex of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone of the invention Feature is: tin atom is seven coordination distortion pentagonal bipyramid configurations in molecule.
Two (2,4- dichloro benzyl) tin complex of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone of the invention has one Fixed thermostabilization range, can be stabilized at 123 DEG C or less.
A kind of two (2,4- dichloro of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone as a second aspect of the invention Benzyl) tin complex preparation method, in the reaction vessel for having nitrogen protection be added two (2,4- dichloro benzyl) stannous chloride, P-nitrobenzoylhydrazide, benzoyl formic acid and solvent anhydrous methanol react 5 ~ 24 h under conditions of temperature is 45 ~ 65 DEG C, cold But, it filters, solvent volatilization crystallization is controlled under conditions of 20 ~ 35 DEG C, obtains yellow transparent crystal, as 2- carbonyl -2- phenyl second Sour p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin complex.
The preparation of two (2,4- dichloro benzyl) tin complex of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone of the invention Feature is: directly obtaining complicated molecule, i.e., one from the relatively easy raw material being easy to get without the separation of intermediate Pot method；It is such to react on economically and environmentally close friend advantageously.
In a preferred embodiment of the invention, described two (2,4- dichloro benzyl) stannous chloride, p-nitrophenyl formyl Hydrazine, benzoyl formic acid three the mass ratio of the material be 1:(1 ~ 1.05): (1.05 ~ 1.15).
In a preferred embodiment of the invention, the solvent anhydrous methanol dosage is every mM two (2,4- dichloros Benzyl) stannous chloride adds 15 ~ 35 milliliters.
A kind of two (2,4- dichloro of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone as the third aspect of the present invention Benzyl) tin complex preparing the application in anticancer drug.
Applicant to above-mentioned two (2,4- dichloro benzyl) tin complex of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone into Anticancer Activity in vitro of having gone determines research, it is thus identified that two (2,4- benzyl dichlorides of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone Base) tin complex have certain anticancer bioactive, that is to say, that the purposes of above-mentioned complex is in preparing anticancer drug Application, be specifically exactly to prepare the application in anti-human lung cancer, human liver cancer and human breast carcinoma drug.
Two (2,4- dichloro benzyl) tin complex of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone of the invention is to people's lung Cancer cell, human liver cancer cell and human breast cancer cell show good anticancer activity, 2- carbonyl -2- phenylacetic acid of the invention The features such as p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin complex anticancer activity is high, at low cost, preparation method is simple be It develops new anticancer drug and provides new way.
Detailed description of the invention
Fig. 1 is the IR spectrogram of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin complex.
Fig. 2 is 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin complex1H NMR Spectrogram.
Fig. 3 is 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin complex13C NMR Spectrogram.
Fig. 4 is 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin complex119Sn NMR spectra.
Fig. 5 is the crystal knot of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin complex Composition.
Fig. 6 is the TG-DTG of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin complex Curve.
Specific embodiment
By following specific embodiments, invention is further described in detail.
Embodiment 1:
The preparation of two (2,4- dichloro benzyl) tin complex of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone:
0.510g (1.0mmol) two (2,4- dichloro benzyl) dichloro is added in the 100mL three-necked flask for having nitrogen protection It is anhydrous to change tin, 0.181g (1.0mmol) p-nitrobenzoylhydrazide, 0.165g (1.1mmol) benzoyl formic acid and 15mL solvent Methanol reacts 8 h under conditions of temperature is 45 ~ 65 DEG C, cooling, filtering, and solvent volatilization knot is controlled under conditions of 20 ~ 35 DEG C Crystalline substance obtains yellow transparent crystal, and as (2, the 4- dichloro benzyl) tin of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two cooperates Object.Yield: 77.6%.Fusing point: 123 ~ 125 DEG C (dec).
Elemental analysis (C30H23Cl4N3O6Sn): calculated value: C 46.07, H 2.96, N 5.37；Measured value: C 46.11, H 2.96, N 5.38.
FT-IR (KBr, ν/cm-1): 3597, 3057, 2943, 2833, 1622, 1579, 1525, 1496, 1469, 1384, 1344, 1317, 1290, 1255, 1172, 1085, 850, 819, 719, 690, 655, 632, 592, 540, 514, 443, 406。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.19-8.22 (m, 2H), 7.85-7.88 (m, 4H), 7.55-7.60 (m, 3H), 7.19 (d, J = 2.1Hz, 2H), 7.10 (d, J = 8.4Hz, 2H), 6.93- 6.95 (dd, J 1 = 8.4Hz, J 2 = 2.1Hz, 2H), 3.50 (s, 3H), 3.43 (d, J = 12.2Hz, 2H), 3.33 (d, J = 12.2Hz, 2H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 173.09, 163.42, 151.63, 150.02, 137.82, 133.40, 133.11, 132.39, 132.11, 131.72, 131.27, 129.35, 128.85, 128.16, 127.91, 127.33, 123.37, 50.90, 30.11。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -279.92。
Crystallographic data: monoclinic system, space group P2 (1)/c, a=1.15807 (7) nm, b=1.02876 (6) nm, C=2.74978 (16) nm, α=γ=90 °, β=98.3990 (10) °, Z=2, V=3.2409 (3) nm3, Dc= 1.603 Mg·m-3, m (MoK α)=1.165 mm-1, F (000)=1560.
Embodiment 2:
The preparation of two (2,4- dichloro benzyl) tin complex of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone:
0.510g (1.0mmol) two (2,4- dichloro benzyl) dichloro is added in the 100mL three-necked flask for having nitrogen protection It is anhydrous to change tin, 0.181g (1.0mmol) p-nitrobenzoylhydrazide, 0.157g (1.05mmol) benzoyl formic acid and 35mL solvent Methanol reacts 5 h under conditions of temperature is 45 ~ 65 DEG C, cooling, filtering, and solvent volatilization knot is controlled under conditions of 20 ~ 35 DEG C Crystalline substance obtains yellow transparent crystal, and as (2, the 4- dichloro benzyl) tin of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two cooperates Object.Yield: 79.5%.Fusing point: 123 ~ 125 DEG C (dec).
Elemental analysis (C30H23Cl4N3O6Sn): calculated value: C 46.07, H 2.96, N 5.37；Measured value: C 46.11, H 2.96, N 5.38.
FT-IR (KBr, ν/cm-1): 3597, 3057, 2943, 2833, 1622, 1579, 1525, 1496, 1469, 1384, 1344, 1317, 1290, 1255, 1172, 1085, 850, 819, 719, 690, 655, 632, 592, 540, 514, 443, 406。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.19-8.22 (m, 2H), 7.85-7.88 (m, 4H), 7.55-7.60 (m, 3H), 7.19 (d, J = 2.1Hz, 2H), 7.10 (d, J = 8.4Hz, 2H), 6.93- 6.95 (dd, J 1 = 8.4Hz, J 2 = 2.1Hz, 2H), 3.50 (s, 3H), 3.43 (d, J = 12.2Hz, 2H), 3.33 (d, J = 12.2Hz, 2H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 173.09, 163.42, 151.63, 150.02, 137.82, 133.40, 133.11, 132.39, 132.11, 131.72, 131.27, 129.35, 128.85, 128.16, 127.91, 127.33, 123.37, 50.90, 30.11。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -279.92。
Crystallographic data: monoclinic system, space group P2 (1)/c, a=1.15807 (7) nm, b=1.02876 (6) nm, C=2.74978 (16) nm, α=γ=90 °, β=98.3990 (10) °, Z=2, V=3.2409 (3) nm3, Dc= 1.603 Mg·m-3, m (MoK α)=1.165 mm-1, F (000)=1560.
Embodiment 3:
The preparation of two (2,4- dichloro benzyl) tin complex of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone:
0.510g (1.0mmol) two (2,4- dichloro benzyl) dichloro is added in the 100mL three-necked flask for having nitrogen protection Change tin, 0.190g (1.05mmol) p-nitrobenzoylhydrazide, 0.173g (1.15mmol) benzoyl formic acid and 25mL solvent without Water methanol reacts 24 h under conditions of temperature is 45 ~ 65 DEG C, cooling, filtering, and solvent is controlled under conditions of 20 ~ 35 DEG C and is waved Hair crystallization, obtains yellow transparent crystal, as 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin is matched Close object.Yield: 78.7%.Fusing point: 123 ~ 125 DEG C (dec).
Elemental analysis (C30H23Cl4N3O6Sn): calculated value: C 46.07, H 2.96, N 5.37；Measured value: C 46.11, H 2.96, N 5.38.
FT-IR (KBr, ν/cm-1): 3597, 3057, 2943, 2833, 1622, 1579, 1525, 1496, 1469, 1384, 1344, 1317, 1290, 1255, 1172, 1085, 850, 819, 719, 690, 655, 632, 592, 540, 514, 443, 406。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.19-8.22 (m, 2H), 7.85-7.88 (m, 4H), 7.55-7.60 (m, 3H), 7.19 (d, J = 2.1Hz, 2H), 7.10 (d, J = 8.4Hz, 2H), 6.93- 6.95 (dd, J 1 = 8.4Hz, J 2 = 2.1Hz, 2H), 3.50 (s, 3H), 3.43 (d, J = 12.2Hz, 2H), 3.33 (d, J = 12.2Hz, 2H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 173.09, 163.42, 151.63, 150.02, 137.82, 133.40, 133.11, 132.39, 132.11, 131.72, 131.27, 129.35, 128.85, 128.16, 127.91, 127.33, 123.37, 50.90, 30.11。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -279.92。
Crystallographic data: monoclinic system, space group P2 (1)/c, a=1.15807 (7) nm, b=1.02876 (6) nm, C=2.74978 (16) nm, α=γ=90 °, β=98.3990 (10) °, Z=2, V=3.2409 (3) nm3, Dc= 1.603 Mg·m-3, m (MoK α)=1.165 mm-1, F (000)=1560.
Embodiment 4:
The preparation of two (2,4- dichloro benzyl) tin complex of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone:
5.100g (10.0mmol) two (2,4- dichloro benzyl) two is added in the 500mL three-necked flask for having nitrogen protection Stannic chloride, 1.864g (10.3mmol) p-nitrobenzoylhydrazide, 1.650g (11.0mmol) benzoyl formic acid and 210mL solvent Anhydrous methanol reacts 22 h under conditions of temperature is 45 ~ 65 DEG C, cooling, and filtering controls solvent under conditions of 20 ~ 35 DEG C Volatilization crystallization, obtains yellow transparent crystal, as 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin Complex.Yield: 75.5%.Fusing point: 123 ~ 125 DEG C (dec).
Elemental analysis (C30H23Cl4N3O6Sn): calculated value: C 46.07, H 2.96, N 5.37；Measured value: C 46.11, H 2.96, N 5.38.
FT-IR (KBr, ν/cm-1): 3597, 3057, 2943, 2833, 1622, 1579, 1525, 1496, 1469, 1384, 1344, 1317, 1290, 1255, 1172, 1085, 850, 819, 719, 690, 655, 632, 592, 540, 514, 443, 406。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.19-8.22 (m, 2H), 7.85-7.88 (m, 4H), 7.55-7.60 (m, 3H), 7.19 (d, J = 2.1Hz, 2H), 7.10 (d, J = 8.4Hz, 2H), 6.93- 6.95 (dd, J 1 = 8.4Hz, J 2 = 2.1Hz, 2H), 3.50 (s, 3H), 3.43 (d, J = 12.2Hz, 2H), 3.33 (d, J = 12.2Hz, 2H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 173.09, 163.42, 151.63, 150.02, 137.82, 133.40, 133.11, 132.39, 132.11, 131.72, 131.27, 129.35, 128.85, 128.16, 127.91, 127.33, 123.37, 50.90, 30.11。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -279.92。
Crystallographic data: monoclinic system, space group P2 (1)/c, a=1.15807 (7) nm, b=1.02876 (6) nm, C=2.74978 (16) nm, α=γ=90 °, β=98.3990 (10) °, Z=2, V=3.2409 (3) nm3, Dc= 1.603 Mg·m-3, m (MoK α)=1.165 mm-1, F (000)=1560.
Test example:
Two (2,4- dichloro benzyl) tin complex of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone of the invention, body Outer anticancer activity 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) can dissolve cell In first a ceremonial jade-ladle, used in libation, with microplate reader measurement characteristic wavelength optical density, can reflect living cells quantity indirectly.
Two (the 2,4- bis- of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone of the preparation of embodiment 1 is measured using mtt assay Chlorobenzyl) inhibition of the tin complex to human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) Activity.
Cell strain and cultivating system: H460, HepG2 and MCF7 cell strain are derived from American tissue incubator (ATCC).With containing RPMI 1640 (GIBICO company) 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 medical fluid (1nM ~ 10 μM) is added separately in each hole according to the concentration gradient of concentration, 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 Test medicine is not added in nutrient solution and cell) and blank group (only plus cultivating medicine, cell and test medicine is not added).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, every hole adds 40 μ L of MTT (being made into 4mg/mL with D-Hanks buffer).After 37 DEG C of placement 4h, upper layer is removed Clear liquid.Every hole adds 150 μ L DMSO, vibrates 5min, makes Formazan crystallization dissolution.Finally, using automatic microplate reader in 570nm The optical density in each hole is detected at wavelength.
Data processing: data processing uses 7.0 program of Graph Pad Prism version, complex IC50Pass through journey Nonlinear regression model (NLRM) in sequence with S-shaped dose response is fitted to obtain.
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, conclusion are as follows: from the data in the table, with 2- carbonyl of the invention Two (2,4- dichloro benzyl) tin complex of base -2- phenylacetic acid p-nitrophenyl formyl hydrazone is used as anticancer drug, to human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) have certain drug effect, can be used as the time of anticancer drug Select compound.
1 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone of table, two (2,4- dichloro benzyl) tin complex anticarcinogen object Outer active testing data.
Human lung cancer Human liver cancer Human breast carcinoma
Cell strain H460 HepG2 MCF7
IC50(μM) 8.21±0.49 4.06±0.49 4.41±0.72
Two (2,4- dichloro benzyl) tin of the 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone cooperation of remaining embodiment preparation Object is surveyed with anticancer activity of the mtt assay to human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) The same test example of method for testing, test result and table 1 are essentially identical.
The above is only a preferred embodiment of the present invention and test example, is not intended to restrict the invention, it is clear that the skill of this field Art personnel can carry out various changes, modification to the present invention without departing from the spirit and scope of the present invention.If to of the invention These modifications and variations within the scope of the claims of the present invention and its equivalent technology, belong to protection model of the invention It encloses.

Claims (6)

1. a kind of 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin complex, for such as flowering structure The complex of formula (I):
(I)
Wherein Ph is phenyl, R 2,4- dichloro benzyl；The complex (I) is crystal structure, and crystallographic data is as follows: Monoclinic system, space group P2 (1)/c, a=1.15807 (7) nm, b=1.02876 (6) nm, c=2.74978 (16) nm, α=γ=90 °, β=98.3990 (10) °, Z=2, V=3.2409 (3) nm3, the Mgm of Dc=1.603-3, m (MoK α)= 1.165 mm-1, F (000)=1560；Tin atom is seven coordination distortion pentagonal bipyramid configurations in molecule；The complex (I) Ir data: FT-IR (KBr, ν/cm-1): 3597, 3057, 2943, 2833, 1622, 1579, 1525, 1496, 1469, 1384, 1344, 1317, 1290, 1255, 1172, 1085, 850, 819, 719, 690, 655, 632, 592, 540, 514, 443, 406；Nuclear-magnetism modal data:1H NMR (500 MHz, CDCl3, δ/ppm): 8.19-8.22 (m, 2H), 7.85-7.88 (m, 4H), 7.55-7.60 (m, 3H), 7.19 (d, J = 2.1Hz, 2H), 7.10 (d, J = 8.4Hz, 2H), 6.93-6.95 (dd, J 1 = 8.4Hz, J 2 = 2.1Hz, 2H), 3.50 (s, 3H), 3.43 (d, J = 12.2Hz, 2H), 3.33 (d, J = 12.2Hz, 2H)；13C NMR (126 MHz, CDCl3, δ/ppm): 173.09, 163.42, 151.63, 150.02, 137.82, 133.40, 133.11, 132.39, 132.11, 131.72, 131.27, 129.35, 128.85, 128.16, 127.91, 127.33, 123.37, 50.90, 30.11；119Sn NMR (187 MHz, CDCl3, δ/ppm): -279.92；The complex (I) it can be stabilized at 123 DEG C or less.
2. 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin complex described in claim 1 Preparation method, it is characterized in that in the reaction vessel for having nitrogen protection be added two (2,4- dichloro benzyl) stannous chloride, to nitre Base benzoyl hydrazine, benzoyl formic acid and solvent anhydrous methanol react 5 ~ 24 h under conditions of temperature is 45 ~ 65 DEG C, cooling, mistake Filter controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains yellow transparent crystal, as 2- carbonyl -2- phenylacetic acid is to nitre Base benzoyl hydrazone two (2,4- dichloro benzyl) tin complex.
3. preparation method as claimed in claim 2, which is characterized in that described two (2,4- dichloro benzyl) stannous chloride, to nitre Base benzoyl hydrazine, benzoyl formic acid three the mass ratio of the material be 1:(1 ~ 1.05): (1.05 ~ 1.15).
4. preparation method as claimed in claim 2, which is characterized in that the solvent anhydrous methanol dosage is every mM two (2,4- dichloro benzyl) stannous chloride adds 15 ~ 35 milliliters.
5. 2- carbonyl -2- phenylacetic acid p-nitrophenyl formyl hydrazone two (2,4- dichloro benzyl) tin complex described in claim 1 exists Prepare the application in anticancer drug.
6. application described in claim 5, wherein cancer cell is human liver cancer cell, human breast cancer cell.
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