CN105777799B - A kind of benzoyl hydrazone Dibenzyltin complex and its preparation method and application - Google Patents

A kind of benzoyl hydrazone Dibenzyltin complex and its preparation method and application Download PDF

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CN105777799B
CN105777799B CN201610254542.0A CN201610254542A CN105777799B CN 105777799 B CN105777799 B CN 105777799B CN 201610254542 A CN201610254542 A CN 201610254542A CN 105777799 B CN105777799 B CN 105777799B
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complex
benzoyl hydrazone
nm
hydrazone dibenzyltin
carbonyl
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CN105777799A (en
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谭宇星
蒋伍玖
张复兴
冯泳兰
庾江喜
朱小明
邝代治
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衡阳师范学院
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00Compounds containing elements of Groups 4 or 14 of the Periodic System
    • C07F7/22Tin compounds
    • C07F7/2284Compounds with one or more Sn-N linkages

Abstract

The invention discloses a kind of 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complexs, are the complex of following structure formula (I), wherein Ph is phenyl, and R is benzyl.The invention also discloses the preparation method of the 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex and preparing the application in anticancer drug.

Description

A kind of benzoyl hydrazone Dibenzyltin complex and its preparation method and application

Technical field

The present invention relates to a kind of 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex and preparation method thereof, with And the 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex is preparing 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.1972, Brown had found Ph for the first time3SnOOCCH3To the growth tool of mouse cancer cell There is inhibiting effect.1980, Crowe etc. chemists' studies have shown that many organo-tin compounds have anti tumor activity in vitro. 1989, American National anticancer research institute(National Cancer Institute)To more than 2,000 kinds of organo-tin compounds into Antitumor activity screening is gone, the results showed that some organo-tin compounds have inhibiting effect to P388 lymphocytic leukemia. 2002, Gielen et al. did comprehensive summing up in the activity to organotin carboxylate's ester compounds, thought many organic after research Tin compound has preferable Anticancer Activity in vitro really.

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 alkali cpd made of being modified as hydrazide kind compound, it Be condensed by aldehydes or ketones and hydrazides, with good bioactivity, stronger coordination ability and multiplicity coordination mode, and And medicine, pesticide, material and in terms of have a wide range of applications.In recent years, domestic and international many researchers couple It compares in terms of bioactivity and in depth studies, and research finds that acylhydrazone has anticancer, sterilization, anti-inflammatory etc. Various active.Therefore, by acylhydrazone class Schiff aar ligand in conjunction with organotin, it is intended to obtain the stronger new chemical combination of bioactivity Object becomes the interested research direction of people.

Chinese patent CN 102718794A disclose a kind of double acylhydrazone class Schiff alkali stannous phenide complexs and its Prepare Antilung gland cancer, colon cancer, leukaemia cell drug in application.

Chinese patent CN 101851251A disclose a kind of acylhydrazone class Schiff aar 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 alkali complex is to human colon cancer cell(HCT-116), human lung adenocarcinoma cell(A549), human umblilical vein endothelial Cell(HUVEC)With compared with strong biological activity, and it is better than carboplatin.

Document(Journal of Organometallic Chemistry, 2013,724: 23-31)Report, series have Machine tin acylhydrazone class Schiff alkali complex, organo-tin compound and acylhydrazone class Schiff aar ligand are respectively to human lung adenocarcinoma Cell(A549), human colon cancer cell(HCT-8), people in loop(hl-60)The inhibiting effect of equal cancer cells.

Document(Bioorganic & Medicinal Chemistry Letters, 2015, 25: 4461- 4463) Report, a variety of acylhydrazone class Schiff aar ligands are to human liver cancer cell(HuH-7)And human lung adenocarcinoma cell(A549)Anticancer it is living Property.

It is the experiment proved that the substance with anticancer activity, the present invention based on acylhydrazone class Schiff alkali organotin complex Selection benzoyl hydrazine, Sodium.beta.-phenylpyruvate react under certain condition with TriphenylphosphineoxComplex, and synthesis has been obtained to human colon carcinoma Cell(Colo205), human liver cancer cell(HepG2), breast cancer cell(MCF7), cervical cancer cell(Hela)It is thin with human lung cancer Born of the same parents(NCI-H460)Complex with certain inhibitory activity provides new approach for exploitation anticancer drug.

Summary of the invention

There is provided a kind of 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complexs for the first object of the present invention.

The second object of the present invention is to provide above-mentioned 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex preparation Method.

The third object of the present invention is to provide above-mentioned 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex and is making Application in standby anticancer drug.

A kind of 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex as the first aspect of the present invention is The complex of structure formula (I)

(I)

Wherein Ph is phenyl, and R is benzyl.

2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex of the invention is through elemental analysis, infrared spectroscopy, core Magnetic resonance spectrum and X-ray single crystal diffraction structural analysis, it is as a result as follows:

Elemental analysis (C62H60N4O8Sn2):Calculated value:C 60.71, H 4.93, N 4.57;Measured value:C 60.74, H 4.99, N 4.59.

FT-IR (KBr, ν/cm-1): 3080, 3059, 3024, 2930, 1630, 1614, 1597, 1391, 1338, 696, 590, 555, 455, 440。

1H NMR (400 MHz, DMSO-d 6) δ(ppm): 7.87 (d, J = 7.1 Hz, 2H), 7.51-7.41 (m, 3H), 7.21-7.13 (m, 3H), 6.96 (d, J = 6.8 Hz, 2H), 6.78 (s, 6H), 6.69(m, 4H), 4.04 (s, 1H), 3.47 (s, 3H), 3.17 (s, 2H,), 2.88-2.81 (m, 4H)。

13C NMR (100 MHz, DMSO-d 6) δ(ppm): 172.75, 164.04, 151.85, 138.30, 135.97, 134.47, 130.72, 128.86, 127.90, 127.80, 127.76, 127.68, 127.10, 125.59, 123.79, 48.38, 37.04, 31.33。

119Sn NMR (187 MHz, DMSO-d 6) δ(ppm): -453.90。

2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex of the invention is crystal structure, crystal three Oblique system, space group P-1, a=0.95601 (4) nm, b=1.22653 (5) nm, c=1.26730 (5) nm, α= 78.19 °, β=71.78 °, γ=86.0410 (10) °, Z=2, V=1.38155 (10) nm3, the Mgm of Dc=1.474-3, m (MoKα)= 0.963 mm-1, F (000)=624.

2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex of the invention is structurally characterized in that:Tin in molecule Atom is seven coordination distortion pentagonal bipyramid configurations.

2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex of the invention has certain thermostabilization range, It can be stabilized at 103 DEG C or less.

A kind of system of 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex as a second aspect of the invention Preparation Method, be added in the reaction vessel for having nitrogen protection TriphenylphosphineoxComplex, benzoyl hydrazine, Sodium.beta.-phenylpyruvate and solvent without Water methanol reacts 5 ~ 24 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 colourless transparent crystal, as 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex.

In a preferred embodiment of the invention, the TriphenylphosphineoxComplex, benzoyl hydrazine, Sodium.beta.-phenylpyruvate 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 of dibenzyl dichloride Tin adds 15 ~ 35 milliliters.

A kind of 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex as the third aspect of the present invention is being made Application in standby anticancer drug.

It is living that applicant has carried out extracorporeal anti-tumor to above-mentioned 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex Property determine research, it is thus identified that 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex has certain Anti-cancer biologic living Property, that is to say, that the purposes of above-mentioned complex is to prepare the application in anticancer drug, is specifically exactly to prepare anti-human knot Intestinal cancer, human liver cancer, human breast carcinoma, human cervical carcinoma, the application in human lung cancer drug.

2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex of the invention is to human colon cancer cell, human liver cancer Cell, human breast cancer cell, human cervical carcinoma cell, human lung carcinoma cell etc. show good anticancer activity, 2- of the invention The features such as carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin 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 -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex.

Fig. 2 is 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex1H NMR spectra.

Fig. 3 is 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex13C NMR spectra.

Fig. 4 is 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex119Sn NMR spectra.

Fig. 5 is the crystal structure figure of 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex.

Fig. 6 is the TG-DTG curve of 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex.

Specific embodiment

By following embodiment, present invention be described in more detail, but should be noted that the scope of the present invention is not implemented by these Any restrictions of example.

Embodiment 1:

The preparation of 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex:

In the 100mL three-necked flask for having nitrogen protection be added 0.372g (1.0mmol) TriphenylphosphineoxComplex, 0.136g (1.0mmol) benzoyl hydrazine, 0.205g (1.1mmol) Sodium.beta.-phenylpyruvate and 25mL solvent anhydrous methanol, in temperature 8 h are reacted under conditions of being 45 ~ 65 DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains colourless Bright crystal, as 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex.Yield:74.4%.Fusing point:103~105℃ (dec)。

Elemental analysis (C62H60N4O8Sn2):Calculated value:C 60.71, H 4.93, N 4.57;Measured value:C 60.74, H 4.99, N 4.59.

FT-IR (KBr, ν/cm-1): 3080, 3059, 3024, 2930, 1630, 1614, 1597, 1391, 1338, 696, 590, 555, 455, 440。

1H NMR (400 MHz, DMSO-d 6) δ(ppm): 7.87 (d, J = 7.1 Hz, 2H), 7.51-7.41 (m, 3H), 7.21-7.13 (m, 3H), 6.96 (d, J = 6.8 Hz, 2H), 6.78 (s, 6H), 6.69(m, 4H), 4.04 (s, 1H), 3.47 (s, 3H), 3.17 (s, 2H,), 2.88-2.81 (m, 4H)。

13C NMR (100 MHz, DMSO-d 6) δ(ppm): 172.75, 164.04, 151.85, 138.30, 135.97, 134.47, 130.72, 128.86, 127.90, 127.80, 127.76, 127.68, 127.10, 125.59, 123.79, 48.38, 37.04, 31.33。

119Sn NMR (187 MHz, DMSO-d 6) δ(ppm): -453.90。

Crystallographic data:Anorthic system, space group P-1, a=0.95601 (4) nm, b=1.22653 (5) nm, c= 1.26730 (5) nm, α=78.19 °, β=71.78 °, γ=86.0410 (10) °, Z=2, V=1.38155 (10) nm3, Dc= 1.474 Mg·m-3, m (MoK α)=0.963 mm-1, F (000)=624.

Embodiment 2:

The preparation of 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex:

In the 100mL three-necked flask for having nitrogen protection be added 0.372g (1.0mmol) TriphenylphosphineoxComplex, 0.136g (1.0mmol) benzoyl hydrazine, 0.195g (1.05mmol) Sodium.beta.-phenylpyruvate and 35mL solvent anhydrous methanol, in temperature 5 h are reacted under conditions of being 45 ~ 65 DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains colourless Bright crystal, as 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex.Yield:77.0%.Fusing point:103~105℃ (dec)。

Elemental analysis (C62H60N4O8Sn2):Calculated value:C 60.71, H 4.93, N 4.57;Measured value:C 60.74, H 4.99, N 4.59.

FT-IR (KBr, ν/cm-1): 3080, 3059, 3024, 2930, 1630, 1614, 1597, 1391, 1338, 696, 590, 555, 455, 440。

1H NMR (400 MHz, DMSO-d 6) δ(ppm): 7.87 (d, J = 7.1 Hz, 2H), 7.51-7.41 (m, 3H), 7.21-7.13 (m, 3H), 6.96 (d, J = 6.8 Hz, 2H), 6.78 (s, 6H), 6.69(m, 4H), 4.04 (s, 1H), 3.47 (s, 3H), 3.17 (s, 2H,), 2.88-2.81 (m, 4H)。

13C NMR (100 MHz, DMSO-d 6) δ(ppm): 172.75, 164.04, 151.85, 138.30, 135.97, 134.47, 130.72, 128.86, 127.90, 127.80, 127.76, 127.68, 127.10, 125.59, 123.79, 48.38, 37.04, 31.33。

119Sn NMR (187 MHz, DMSO-d 6) δ(ppm): -453.90。

Crystallographic data:Anorthic system, space group P-1, a=0.95601 (4) nm, b=1.22653 (5) nm, c= 1.26730 (5) nm, α=78.19 °, β=71.78 °, γ=86.0410 (10) °, Z=2, V=1.38155 (10) nm3, Dc= 1.474 Mg·m-3, m (MoK α)=0.963 mm-1, F (000)=624.

Embodiment 3:

The preparation of 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex:

In the 100mL three-necked flask for having nitrogen protection be added 0.372g (1.0mmol) TriphenylphosphineoxComplex, 0.142g (1.05mmol) benzoyl hydrazine, 0.214g (1.15mmol) Sodium.beta.-phenylpyruvate and 30mL solvent anhydrous methanol, in temperature Degree reacts 15 h under conditions of being 45 ~ 65 DEG C, cooling, filtering, and solvent volatilization crystallization is controlled under conditions of 20 ~ 35 DEG C, obtains nothing Color transparent crystal, as 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex.Yield:78.2%.Fusing point:103~ 105℃(dec)。

Elemental analysis (C62H60N4O8Sn2):Calculated value:C 60.71, H 4.93, N 4.57;Measured value:C 60.74, H 4.99, N 4.59.

FT-IR (KBr, ν/cm-1): 3080, 3059, 3024, 2930, 1630, 1614, 1597, 1391, 1338, 696, 590, 555, 455, 440。

1H NMR (400 MHz, DMSO-d 6) δ(ppm): 7.87 (d, J = 7.1 Hz, 2H), 7.51-7.41 (m, 3H), 7.21-7.13 (m, 3H), 6.96 (d, J = 6.8 Hz, 2H), 6.78 (s, 6H), 6.69(m, 4H), 4.04 (s, 1H), 3.47 (s, 3H), 3.17 (s, 2H,), 2.88-2.81 (m, 4H)。

13C NMR (100 MHz, DMSO-d 6) δ(ppm): 172.75, 164.04, 151.85, 138.30, 135.97, 134.47, 130.72, 128.86, 127.90, 127.80, 127.76, 127.68, 127.10, 125.59, 123.79, 48.38, 37.04, 31.33。

119Sn NMR (187 MHz, DMSO-d 6) δ(ppm): -453.90。

Crystallographic data:Anorthic system, space group P-1, a=0.95601 (4) nm, b=1.22653 (5) nm, c= 1.26730 (5) nm, α=78.19 °, β=71.78 °, γ=86.0410 (10) °, Z=2, V=1.38155 (10) nm3, Dc= 1.474 Mg·m-3, m (MoK α)=0.963 mm-1, F (000)=624.

Embodiment 4:

The preparation of 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex:

In the 250mL three-necked flask for having nitrogen protection be added 1.860g (5.0mmol) TriphenylphosphineoxComplex, 0.694g (5.1mmol) benzoyl hydrazine, 1.004g (5.4mmol) Sodium.beta.-phenylpyruvate and 100mL solvent anhydrous methanol, in temperature 20 h are reacted under conditions of being 45 ~ 65 DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains colourless Transparent crystal, as 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex.Yield:73.9%.Fusing point:103~105 ℃(dec)。

Elemental analysis (C62H60N4O8Sn2):Calculated value:C 60.71, H 4.93, N 4.57;Measured value:C 60.74, H 4.99, N 4.59.

FT-IR (KBr, ν/cm-1): 3080, 3059, 3024, 2930, 1630, 1614, 1597, 1391, 1338, 696, 590, 555, 455, 440。

1H NMR (400 MHz, DMSO-d 6) δ(ppm): 7.87 (d, J = 7.1 Hz, 2H), 7.51-7.41 (m, 3H), 7.21-7.13 (m, 3H), 6.96 (d, J = 6.8 Hz, 2H), 6.78 (s, 6H), 6.69(m, 4H), 4.04 (s, 1H), 3.47 (s, 3H), 3.17 (s, 2H,), 2.88-2.81 (m, 4H)。

13C NMR (100 MHz, DMSO-d 6) δ(ppm): 172.75, 164.04, 151.85, 138.30, 135.97, 134.47, 130.72, 128.86, 127.90, 127.80, 127.76, 127.68, 127.10, 125.59, 123.79, 48.38, 37.04, 31.33。

119Sn NMR (187 MHz, DMSO-d 6) δ(ppm): -453.90。

Crystallographic data:Anorthic system, space group P-1, a=0.95601 (4) nm, b=1.22653 (5) nm, c= 1.26730 (5) nm, α=78.19 °, β=71.78 °, γ=86.0410 (10) °, Z=2, V=1.38155 (10) nm3, Dc= 1.474 Mg·m-3, m (MoK α)=0.963 mm-1, F (000)=624.

Embodiment 5:

The preparation of 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex:

In the 250mL three-necked flask for having nitrogen protection be added 1.860g (5.0mmol) TriphenylphosphineoxComplex, 0.707g (5.2mmol) benzoyl hydrazine, 1.042g (5.6mmol) Sodium.beta.-phenylpyruvate and 150mL solvent anhydrous methanol, in temperature 22 h are reacted under conditions of being 45 ~ 65 DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains colourless Transparent crystal, as 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex.Yield:73.2%.Fusing point:103~105 ℃(dec)。

Elemental analysis (C62H60N4O8Sn2):Calculated value:C 60.71, H 4.93, N 4.57;Measured value:C 60.74, H 4.99, N 4.59.

FT-IR (KBr, ν/cm-1): 3080, 3059, 3024, 2930, 1630, 1614, 1597, 1391, 1338, 696, 590, 555, 455, 440。

1H NMR (400 MHz, DMSO-d 6) δ(ppm): 7.87 (d, J = 7.1 Hz, 2H), 7.51-7.41 (m, 3H), 7.21-7.13 (m, 3H), 6.96 (d, J = 6.8 Hz, 2H), 6.78 (s, 6H), 6.69(m, 4H), 4.04 (s, 1H), 3.47 (s, 3H), 3.17 (s, 2H,), 2.88-2.81 (m, 4H)。

13C NMR (100 MHz, DMSO-d 6) δ(ppm): 172.75, 164.04, 151.85, 138.30, 135.97, 134.47, 130.72, 128.86, 127.90, 127.80, 127.76, 127.68, 127.10, 125.59, 123.79, 48.38, 37.04, 31.33。

119Sn NMR (187 MHz, DMSO-d 6) δ(ppm): -453.90。

Crystallographic data:Anorthic system, space group P-1, a=0.95601 (4) nm, b=1.22653 (5) nm, c= 1.26730 (5) nm, α=78.19 °, β=71.78 °, γ=86.0410 (10) °, Z=2, V=1.38155 (10) nm3, Dc= 1.474 Mg·m-3, m (MoK α)=0.963 mm-1, F (000)=624.

Embodiment 6:

The preparation of 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex:

In the 250mL three-necked flask for having nitrogen protection be added 3.720g (10.0mmol) TriphenylphosphineoxComplex, 1.387g (10.2mmol) benzoyl hydrazine, 1.972g (10.6mmol) Sodium.beta.-phenylpyruvate and 150mL solvent anhydrous methanol, in temperature Degree reacts 24 h under conditions of being 45 ~ 65 DEG C, cooling, filtering, and solvent volatilization crystallization is controlled under conditions of 20 ~ 35 DEG C, obtains nothing Color transparent crystal, as 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex.Yield:71.7%.Fusing point:103~ 105℃(dec)。

Elemental analysis (C62H60N4O8Sn2):Calculated value:C 60.71, H 4.93, N 4.57;Measured value:C 60.74, H 4.99, N 4.59.

FT-IR (KBr, ν/cm-1): 3080, 3059, 3024, 2930, 1630, 1614, 1597, 1391, 1338, 696, 590, 555, 455, 440。

1H NMR (400 MHz, DMSO-d 6) δ(ppm): 7.87 (d, J = 7.1 Hz, 2H), 7.51-7.41 (m, 3H), 7.21-7.13 (m, 3H), 6.96 (d, J = 6.8 Hz, 2H), 6.78 (s, 6H), 6.69(m, 4H), 4.04 (s, 1H), 3.47 (s, 3H), 3.17 (s, 2H,), 2.88-2.81 (m, 4H)。

13C NMR (100 MHz, DMSO-d 6) δ(ppm): 172.75, 164.04, 151.85, 138.30, 135.97, 134.47, 130.72, 128.86, 127.90, 127.80, 127.76, 127.68, 127.10, 125.59, 123.79, 48.38, 37.04, 31.33。

119Sn NMR (187 MHz, DMSO-d 6) δ(ppm): -453.90。

Crystallographic data:Anorthic system, space group P-1, a=0.95601 (4) nm, b=1.22653 (5) nm, c= 1.26730 (5) nm, α=78.19 °, β=71.78 °, γ=86.0410 (10) °, Z=2, V=1.38155 (10) nm3, Dc= 1.474 Mg·m-3, m (MoK α)=0.963 mm-1, F (000)=624.

Test example:

2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex of the invention, Anticancer Activity in vitro measurement are It is realized by MTT experiment method.

MTT analytic approach:

3- (4,5-Dimethylthiazol-2-yl) -2,5-diphenyltetrazolium is restored with metabolism Based on bromide.Succinate dehydrogenase in living cells mitochondria can make exogenous MTT be reduced to the bluish violet of water-insoluble Crystallize first a ceremonial jade-ladle, used in libation(Formazan)And be deposited in cell, and dead cell is without this function.Dimethyl sulfoxide(DMSO)Cell can be dissolved In first a ceremonial jade-ladle, used in libation, with microplate reader measurement characteristic wavelength optical density, can reflect living cells quantity indirectly.

2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin the complex pair of the preparation of embodiment 1 is measured using mtt assay Human colon cancer cell(Colo205), human liver cancer cell(HepG2), human breast cancer cell(MCF7), human cervical carcinoma cell (Hela)And human lung carcinoma cell(NCI-H460)Inhibitory activity.

Cell strain and cultivating system:Colo205, HepG2, MCF7, Hela and NCI-H460 cell strain are derived from American tissue Incubator(ATCC).With the RPMI 1640 for containing 10% fetal calf serum(GIBICO company)Culture medium, 5%(Volume fraction)CO2、 In vitro culture is carried out in 37 DEG C of saturated humidity incubators.

Test process:Medical fluid will be tested(0.1ng/mL~10ug/mL)It is added separately to according to the concentration gradient of concentration each Kong Zhong, each concentration set 6 parallel holes.Experiment is divided into drug study group(It is separately added into the test medicine of various concentration), control group (Only add culture solution and cell, test medicine is not added)And blank group(Only plus medicine is cultivated, cell and test medicine is not added).After dosing Orifice plate is placed in 37 DEG C, 5%CO272h is cultivated in incubator.The activity of control drug is measured according to the method for test sample.It is cultivating In orifice plate after 72h, every hole adds MTT 40uL(4mg/mL is made into D-Hanks buffer).After 37 DEG C of placement 4h, remove Supernatant liquor.Every hole adds 150uL DMSO, vibrates 5min, makes Formazan crystallization dissolution.Finally, being existed using automatic microplate reader The optical density in each hole is detected at 570nm wavelength.

Data processing:Data processing uses 5.0 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.

With MTT analytic approach to human colon cancer cell(Colo205), human liver cancer cell(HepG2), human breast cancer cell (MCF7), human cervical carcinoma cell(Hela)And human lung carcinoma cell(NCI-H460)Cell strain is analyzed, its IC is measured50Value, The results are shown in Table 1, and conclusion is:From the data in the table, with 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone dibenzyl of the invention Tin complex is used as anticancer drug, to human colon cancer cell(Colo205), human liver cancer cell(HepG2), human breast cancer cell (MCF7), human cervical carcinoma cell(Hela)And human lung carcinoma cell(NCI-H460)With certain drug effect, anticarcinogen can be used as The candidate compound of object.

1 2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin complex anticancer drug external activity test data of table.

2- carbonyl -3- phenylpropionic acid benzoyl hydrazone Dibenzyltin the complex of remaining embodiment preparation ties people with mtt assay Colon-cancer cell(Colo205), human liver cancer cell(HepG2), human breast cancer cell(MCF7), human cervical carcinoma cell(Hela)With Human lung carcinoma cell(NCI-H460)The same test example of anticancer activity test method, test result and table 1 are essentially identical.

Claims (6)

1. a kind of benzoyl hydrazone Dibenzyltin complex is the complex of following structure formula (I):
(I)
Wherein Ph is phenyl, and R is benzyl, and the complex (I) is crystal structure, and crystallographic data is as follows:Anorthic system, Space group P-1, a=0.95601 (4) nm, b=1.22653 (5) nm, c=1.26730 (5) nm, α=78.19 °, β =71.78 °, γ=86.0410 (10) °, Z=2, V=1.38155 (10) nm3, the Mgm of Dc=1.474-3, m (MoK α)= 0.963 mm-1, F (000)=624;Tin atom is seven coordination distortion pentagonal bipyramid configurations in molecule;The complex (I) Ir data:FT-IR (KBr, ν/cm-1): 3080, 3059, 3024, 2930, 1630, 1614, 1597, 1391, 1338, 696, 590, 555, 455, 440;Its nuclear-magnetism modal data:1H NMR (400 MHz, DMSO-d 6) δ (ppm): 7.87 (d, J = 7.1 Hz, 2H), 7.51-7.41 (m, 3H), 7.21-7.13 (m, 3H), 6.96 (d, J = 6.8 Hz, 2H), 6.78 (s, 6H), 6.69(m, 4H), 4.04 (s, 1H), 3.47 (s, 3H), 3.17 (s, 2H,), 2.88-2.81 (m, 4H);13C NMR (100 MHz, DMSO-d 6) δ(ppm): 172.75, 164.04, 151.85, 138.30, 135.97, 134.47, 130.72, 128.86, 127.90, 127.80, 127.76, 127.68, 127.10, 125.59, 123.79, 48.38, 37.04, 31.33;119Sn NMR (187 MHz, DMSO-d 6) δ(ppm): -453.90;The complex (I) can be stabilized at 103 DEG C or less.
2. the preparation method of benzoyl hydrazone Dibenzyltin complex described in claim 1, it is characterized in that there is nitrogen protection TriphenylphosphineoxComplex, benzoyl hydrazine, Sodium.beta.-phenylpyruvate and solvent anhydrous methanol are added in reaction vessel, is 45 ~ 65 in temperature 5 ~ 24 h are reacted under conditions of DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains colorless and transparent crystalline substance Body, as benzoyl hydrazone Dibenzyltin complex.
3. preparation method as claimed in claim 2, which is characterized in that the TriphenylphosphineoxComplex, benzoyl hydrazine, propiophenone The mass ratio of the material of sour sodium three is 1:(1~1.05):(1.05~1.15).
4. preparation method as claimed in claim 2, which is characterized in that the solvent anhydrous methanol dosage is every mM of dibenzyl Base stannous chloride adds 15 ~ 35 milliliters.
5. benzoyl hydrazone Dibenzyltin complex described in claim 1 is preparing the application in anticancer drug.
6. application described in claim 5, wherein the cancer cell is human liver cancer cell, human cervical carcinoma cell.
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