CN105384770B - A kind of 2 carbonyl propionic acid salicyloyl hydrazones two are to methyl-benzyl tin complex and its preparation method and application - Google Patents

A kind of 2 carbonyl propionic acid salicyloyl hydrazones two are to methyl-benzyl tin complex and its preparation method and application Download PDF

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CN105384770B
CN105384770B CN201510769367.4A CN201510769367A CN105384770B CN 105384770 B CN105384770 B CN 105384770B CN 201510769367 A CN201510769367 A CN 201510769367A CN 105384770 B CN105384770 B CN 105384770B
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methyl
benzyl
nm
complex
carbonyl propionic
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CN105384770A (en
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蒋伍玖
庾江喜
谭宇星
邝代治
冯泳兰
张复兴
朱小明
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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 propionic acid salicyloyl hydrazones two to methyl-benzyl tin complex, for the complex of following structure formula (I), wherein R is to methyl-benzyl.The invention also discloses the preparation method of the 2 carbonyl propionic acid salicyloyl hydrazone two to methyl-benzyl tin complex and the application in cancer therapy drug is prepared.

Description

A kind of 2- carbonyl propionic acids salicyloyl hydrazone two is to methyl-benzyl tin complex and its preparation side Method and application

Technical field

The present invention relates to a kind of 2- carbonyl propionic acids salicyloyl hydrazone two to methyl-benzyl tin complex and preparation method thereof, and The application of the 2- carbonyl propionic acids salicyloyl hydrazone two to methyl-benzyl tin complex in cancer therapy drug is prepared.

Background technology

Organotin is a kind of metallo-organic compound containing Sn-C keys.Researcher just notices before very early The Anticancer Activity in vitro of organo-tin compound.1972, Brown had found Ph first3SnOOCCH3Growth tool to mouse cancer cell There is inhibitory action.1980, the research of the chemist such as Crowe showed that many organo-tin compounds have anti tumor activity in vitro. 1989, American National anticancer research institute (National Cancer Institute) entered to more than 2,000 kinds of organo-tin compounds Antitumor activity screening is gone, the results showed that some organo-tin compounds have inhibitory action to P388 lymphocytic leukemias. 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.

Research shows that the organic group connected on organic tin atom and the part for participating in being coordinated decide organo-tin compound Bioactivity, select some in itself have good biological activity organic ligand and organotin in tin atom coordination cause The great interest of people.Acylhydrazone is to be modified a kind of Schiff alkali cpds formed by hydrazide kind compound, it By aldehydes or ketones and hydrazides condensation form, there is good bioactivity, stronger coordination ability and various coordination mode, and And had a wide range of applications in medicine, agricultural chemicals, material and analytical reagent etc..In recent years, domestic and international many researchers couple It compares in terms of bioactivity and in depth studied, and research finds that acylhydrazone has anticancer, sterilization, anti-inflammatory etc. Various active.Therefore, acylhydrazone class Schiff aar ligands are combined with organotin, it is intended to obtain the stronger new chemical combination of bioactivity Thing, turn into people's research direction interested.

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 medicine in application.

Chinese patent CN 101851251A disclose a kind of acylhydrazone class Schiff aar ligands dibutyl tin complex and Its application in the medicine for preparing treatment liver cancer, adenocarcinoma of lung, breast cancer, prostate cancer, colon cancer or early young grain leukaemia.

Document(Journal of Organometallic Chemistry, 2014,75: 83-91)Report, organotin Acylhydrazone class Schiff alkali complexs are to human colon cancer cell(HCT-116), human lung adenocarcinoma cell(A549), human umblilical vein endothelial Cell (HUVEC) has compared with strong biological activity, and 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 ligands are respectively to human lung adenocarcinoma Cell(A549), human colon cancer cell(HCT-8), people in loop(hl-60)Deng the inhibitory action of cancer cell.

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 live Property.

It is that the experiment proved that the material with active anticancer based on acylhydrazone class Schiff alkali organotin complexes, the present invention Selection salicylyl hydrazine, Sodium Pyruvate react under certain condition with two pairs of methyl-benzyl stannous chloride, and synthesis has obtained tying people Colon-cancer cell(Colo205), human liver cancer cell(HepG2), breast cancer cell(MCF7), cervical cancer cell(Hela)With people's lung Cancer cell(NCI-H460)Complex with certain inhibitory activity, new approach is provided for exploitation cancer therapy drug.

The content of the invention

The first object of the present invention there is provided a kind of 2- carbonyl propionic acids salicyloyl hydrazone two to methyl-benzyl tin complex.

The second object of the present invention is to provide above-mentioned 2- carbonyl propionic acids salicyloyl hydrazone two and is is prepared by methyl-benzyl tin complex Method.

The third object of the present invention is to provide above-mentioned 2- carbonyl propionic acids salicyloyl hydrazone two and methyl-benzyl tin complex is being made Application in standby cancer therapy drug.

A kind of 2- carbonyl propionic acids salicyloyl hydrazone two as the first aspect of the present invention is to methyl-benzyl tin complex, for knot The complex of structure formula (I)

(I)

Wherein R is to methyl-benzyl.

The 2- carbonyl propionic acids salicyloyl hydrazone two of the present invention is to methyl-benzyl tin complex through elementary analysis, infrared spectrum, purple Outside-visible spectrum, nuclear magnetic resoance spectrum and X-ray single crystal diffraction structural analysis, it is as a result as follows:

Elementary analysis (C54H60N4O10Sn2):Calculated value:C 55.79, H 5.20, N 4.82;Measured value:C 55.84, H 5.26, N 4.89.

FT-IR (KBr, ν/cm-1): 3453, 3019, 2920, 2849, 1616, 1587, 1381, 1321, 1252, 592, 555, 505, 446。

UV-vis (DMSO), λ max (nm): 334。

1H NMR (400 MHz, CDCl3) δ(ppm): 11.22 (s, 1H), 8.10 (d, J = 7.6 Hz, 1H), 7.49-7.45 (t, J = 7.9 Hz, 1H), 7.01-6.95 (m, 2H), 6.84-6.75 (m, 8H), 3.50 (s, 3H), 3.31 (s, 4H), 2.18-2.12 (s, 6H), 1.91(s, 3H)。

13C NMR (100 MHz, CDCl3) δ(ppm): 175.49, 160.78, 150.96, 135.48, 134.48, 132.76, 130.30, 129.27, 129.00, 128.25, 118.89, 117.31, 115.53, 35.76, 20.74, 12.80。

The 2- carbonyl propionic acids salicyloyl hydrazone two of the present invention is crystal structure to methyl-benzyl tin complex, and its crystal is monocline Crystallographic system, space group P2 (1)/n, a=1.14663 (7) nm, b=1.23714 (7) nm, c=1.92461 (12) nm, α= γ=90 °, β=98.6890 (10) °, Z=4, V=2.6988 (3) nm3, the Mgm of Dc=1.430-3, m (MoK α)= 0.984 mm-1, F (000)=1184.

The 2- carbonyl propionic acids salicyloyl hydrazone two of the present invention is structurally characterized in that to methyl-benzyl tin complex:Tin is former in molecule Son is seven coordination distortion pentagonal bipyramid configurations.

A kind of 2- carbonyl propionic acids salicyloyl hydrazone two as the second aspect of the present invention is to the system of methyl-benzyl tin complex Preparation Method, two pairs of methyl-benzyl stannous chloride, salicylyl hydrazine, Sodium Pyruvate and molten are added in the reaction vessel for having nitrogen to protect Agent absolute methanol, 5 ~ 24 h are reacted under conditions of being 45 ~ 65 DEG C in temperature, cools down, filtering, is controlled under conditions of 20 ~ 35 DEG C Solvent volatilization crystallization, obtains colourless transparent crystal, as 2- carbonyl propionic acids salicyloyl hydrazone two is to methyl-benzyl tin complex.

In a preferred embodiment of the invention, two pairs of methyl-benzyl stannous chloride, salicylyl hydrazine, Sodium Pyruvates The amount ratio of the material of three is 1:(1~1.05):(1.05~1.15).

In a preferred embodiment of the invention, the solvent absolute methanol dosage is every mM of two pairs of methyl-benzyls Stannous chloride adds 15 ~ 35 milliliters.

The 2- carbonyl propionic acids salicyloyl hydrazone two of the present invention is one kettle way to methyl-benzyl tin complex preparation method, Ji Jiangquan Portion's raw material is added in reactor together directly to react, and without the separation of intermediate, 2- carbonyl propionic acid salicyloyls are directly prepared Hydrazone two is to methyl-benzyl tin complex.And the customary preparation methods of this area are that part is first prepared, then by part with containing gold Complex is prepared in the starting compound reaction of category, and 2- carbonyl propionic acids salicyloyl hydrazone two of the invention coordinates methyl-benzyl tin Thing preparation method compares this area customary preparation methods, has the last handling process for saving intermediate steps, saves substantial amounts of The advantages that human and material resources, financial resources.

A kind of 2- carbonyl propionic acids salicyloyl hydrazone two as the third aspect of the present invention is being made to methyl-benzyl tin complex Application in standby cancer therapy drug.

Applicant has carried out extracorporeal anti-tumor work to above-mentioned 2- carbonyl propionic acids salicyloyl hydrazone two to methyl-benzyl tin complex Property determine research, it is thus identified that there is 2- carbonyl propionic acids salicyloyl hydrazone two certain Anti-cancer biologic to live to methyl-benzyl tin complex Property, that is to say, that the purposes of above-mentioned complex is the application in cancer therapy drug is prepared, and is exactly specifically to prepare anti-human knot Application in intestinal cancer, human liver cancer, human breast carcinoma, human cervical carcinoma, human lung cancer medicine.

The 2- carbonyl propionic acids salicyloyl hydrazone two of the present invention is thin to human colon cancer cell, human liver cancer to methyl-benzyl tin complex Born of the same parents, human breast cancer cell, human cervical carcinoma cell, human lung carcinoma cell etc. show good active anticancer, 2- carbonyls of the invention Base propionic acid salicyloyl hydrazone two is to the features such as methyl-benzyl tin complex active anticancer is high, cost is low, preparation method is simple, for exploitation New cancer therapy drug provides new way.

Brief description of the drawings

Fig. 1 is IR spectrogram of the 2- carbonyl propionic acids salicyloyl hydrazone two to methyl-benzyl tin complex.

Fig. 2 is UV-Vis spectrogram of the 2- carbonyl propionic acids salicyloyl hydrazone two to methyl-benzyl tin complex.

Fig. 3 is 2- carbonyl propionic acids salicyloyl hydrazone two to methyl-benzyl tin complex1H NMR spectras.

Fig. 4 is 2- carbonyl propionic acids salicyloyl hydrazone two to methyl-benzyl tin complex13C NMR spectras.

Fig. 5 is crystal structure figure of the 2- carbonyl propionic acids salicyloyl hydrazone two to methyl-benzyl tin complex.

Fig. 6 is TG-DTG curve of the 2- carbonyl propionic acids salicyloyl hydrazone two to methyl-benzyl tin complex.

Embodiment

The present invention is further described by following examples, but should be noted that the scope of the present invention is not implemented by these Any restrictions of example.

Embodiment 1:

Two preparation to methyl-benzyl tin complex of salicyloyl hydrazone of 2- carbonyl propionic acids:

0.400g (1.0mmol) two pairs of methyl-benzyl dichlorides are added in the 100mL three-necked flasks for having nitrogen to protect Tin, 0.152g (1.0mmol) salicylyl hydrazine, 0.121g (1.1mmol) Sodium Pyruvates and 25mL solvent absolute methanols, in temperature To react 8 h under conditions of 45 ~ 65 DEG C, cool down, filtering, solvent volatilization crystallization is controlled under conditions of 20 ~ 35 DEG C, is obtained colourless Bright crystal, as 2- carbonyl propionic acids salicyloyl hydrazone two are to methyl-benzyl tin complex.Yield:75.4%.Fusing point:82~84℃ (dec)。

Elementary analysis (C54H60N4O10Sn2):Calculated value:C 55.79, H 5.20, N 4.82;Measured value:C 55.84, H 5.26, N 4.89.

FT-IR (KBr, ν/cm-1): 3453, 3019, 2920, 2849, 1616, 1587, 1381, 1321, 1252, 592, 555, 505, 446。

UV-vis (DMSO), λ max (nm): 334。

1H NMR (400 MHz, CDCl3) δ(ppm): 11.22 (s, 1H), 8.10 (d, J = 7.6 Hz, 1H), 7.49-7.45 (t, J = 7.9 Hz, 1H), 7.01-6.95 (m, 2H), 6.84-6.75 (m, 8H), 3.50 (s, 3H), 3.31 (s, 4H), 2.18-2.12 (s, 6H), 1.91(s, 3H)。

13C NMR (100 MHz, CDCl3) δ(ppm): 175.49, 160.78, 150.96, 135.48, 134.48, 132.76, 130.30, 129.27, 129.00, 128.25, 118.89, 117.31, 115.53, 35.76, 20.74, 12.80。

Crystallographic data:Monoclinic system, space group P2 (1)/n, a=1.14663 (7) nm, b=1.23714 (7) Nm, c=1.92461 (12) nm, α=γ=90 °, β=98.6890 (10) °, Z=4, V=2.6988 (3) nm3, Dc= 1.430 Mg·m-3, m (MoK α)=0.984 mm-1, F (000)=1184.

Embodiment 2:

Two preparation to methyl-benzyl tin complex of salicyloyl hydrazone of 2- carbonyl propionic acids:

0.400g (1.0mmol) two pairs of methyl-benzyl dichlorides are added in the 100mL three-necked flasks for having nitrogen to protect Tin, 0.152g (1.0mmol) salicylyl hydrazine, 0.116g (1.05mmol) Sodium Pyruvates and 35mL solvent absolute methanols, in temperature Spend to react 5 h under conditions of 45 ~ 65 DEG C, cool down, filtering, solvent volatilization crystallization is controlled under conditions of 20 ~ 35 DEG C, is obtained colourless Transparent crystal, as 2- carbonyl propionic acids salicyloyl hydrazone two are to methyl-benzyl tin complex.Yield:77.0%.Fusing point:82~84℃ (dec)。

Elementary analysis (C54H60N4O10Sn2):Calculated value:C 55.79, H 5.20, N 4.82;Measured value:C 55.84, H 5.26, N 4.89.

FT-IR (KBr, ν/cm-1): 3453, 3019, 2920, 2849, 1616, 1587, 1381, 1321, 1252, 592, 555, 505, 446。

UV-vis (DMSO), λ max (nm): 334。

1H NMR (400 MHz, CDCl3) δ(ppm): 11.22 (s, 1H), 8.10 (d, J = 7.6 Hz, 1H), 7.49-7.45 (t, J = 7.9 Hz, 1H), 7.01-6.95 (m, 2H), 6.84-6.75 (m, 8H), 3.50 (s, 3H), 3.31 (s, 4H), 2.18-2.12 (s, 6H), 1.91(s, 3H)。

13C NMR (100 MHz, CDCl3) δ(ppm): 175.49, 160.78, 150.96, 135.48, 134.48, 132.76, 130.30, 129.27, 129.00, 128.25, 118.89, 117.31, 115.53, 35.76, 20.74, 12.80。

Crystallographic data:Monoclinic system, space group P2 (1)/n, a=1.14663 (7) nm, b=1.23714 (7) Nm, c=1.92461 (12) nm, α=γ=90 °, β=98.6890 (10) °, Z=4, V=2.6988 (3) nm3, Dc= 1.430 Mg·m-3, m (MoK α)=0.984 mm-1, F (000)=1184.

Embodiment 3:

Two preparation to methyl-benzyl tin complex of salicyloyl hydrazone of 2- carbonyl propionic acids:

0.400g (1.0mmol) two pairs of methyl-benzyl dichlorides are added in the 100mL three-necked flasks for having nitrogen to protect Tin, 0.160g (1.05mmol) salicylyl hydrazine, 0.127g (1.15mmol) Sodium Pyruvates and 30mL solvent absolute methanols, in temperature Spend to react 15 h under conditions of 45 ~ 65 DEG C, cool down, filtering, solvent volatilization crystallization is controlled under conditions of 20 ~ 35 DEG C, obtains nothing Color transparent crystal, as 2- carbonyl propionic acids salicyloyl hydrazone two are to methyl-benzyl tin complex.Yield:78.2%.Fusing point:82~84℃ (dec)。

Elementary analysis (C54H60N4O10Sn2):Calculated value:C 55.79, H 5.20, N 4.82;Measured value:C 55.84, H 5.26, N 4.89.

FT-IR (KBr, ν/cm-1): 3453, 3019, 2920, 2849, 1616, 1587, 1381, 1321, 1252, 592, 555, 505, 446。

UV-vis (DMSO), λ max (nm): 334。

1H NMR (400 MHz, CDCl3) δ(ppm): 11.22 (s, 1H), 8.10 (d, J = 7.6 Hz, 1H), 7.49-7.45 (t, J = 7.9 Hz, 1H), 7.01-6.95 (m, 2H), 6.84-6.75 (m, 8H), 3.50 (s, 3H), 3.31 (s, 4H), 2.18-2.12 (s, 6H), 1.91(s, 3H)。

13C NMR (100 MHz, CDCl3) δ(ppm): 175.49, 160.78, 150.96, 135.48, 134.48, 132.76, 130.30, 129.27, 129.00, 128.25, 118.89, 117.31, 115.53, 35.76, 20.74, 12.80。

Crystallographic data:Monoclinic system, space group P2 (1)/n, a=1.14663 (7) nm, b=1.23714 (7) Nm, c=1.92461 (12) nm, α=γ=90 °, β=98.6890 (10) °, Z=4, V=2.6988 (3) nm3, Dc= 1.430 Mg·m-3, m (MoK α)=0.984 mm-1, F (000)=1184.

Embodiment 4:

Two preparation to methyl-benzyl tin complex of salicyloyl hydrazone of 2- carbonyl propionic acids:

2.000g (5.0mmol) two pairs of methyl-benzyl dichlorides are added in the 250mL three-necked flasks for having nitrogen to protect Tin, 0.775g (5.1mmol) salicylyl hydrazine, 0.594g (5.4mmol) Sodium Pyruvates and 100mL solvent absolute methanols, in temperature Spend to react 20 h under conditions of 45 ~ 65 DEG C, cool down, filtering, solvent volatilization crystallization is controlled under conditions of 20 ~ 35 DEG C, obtains nothing Color transparent crystal, as 2- carbonyl propionic acids salicyloyl hydrazone two are to methyl-benzyl tin complex.Yield:73.9%.Fusing point:82~84℃ (dec)。

Elementary analysis (C54H60N4O10Sn2):Calculated value:C 55.79, H 5.20, N 4.82;Measured value:C 55.84, H 5.26, N 4.89.

FT-IR (KBr, ν/cm-1): 3453, 3019, 2920, 2849, 1616, 1587, 1381, 1321, 1252, 592, 555, 505, 446。

UV-vis (DMSO), λ max (nm): 334。

1H NMR (400 MHz, CDCl3) δ(ppm): 11.22 (s, 1H), 8.10 (d, J = 7.6 Hz, 1H), 7.49-7.45 (t, J = 7.9 Hz, 1H), 7.01-6.95 (m, 2H), 6.84-6.75 (m, 8H), 3.50 (s, 3H), 3.31 (s, 4H), 2.18-2.12 (s, 6H), 1.91(s, 3H)。

13C NMR (100 MHz, CDCl3) δ(ppm): 175.49, 160.78, 150.96, 135.48, 134.48, 132.76, 130.30, 129.27, 129.00, 128.25, 118.89, 117.31, 115.53, 35.76, 20.74, 12.80。

Crystallographic data:Monoclinic system, space group P2 (1)/n, a=1.14663 (7) nm, b=1.23714 (7) Nm, c=1.92461 (12) nm, α=γ=90 °, β=98.6890 (10) °, Z=4, V=2.6988 (3) nm3, Dc= 1.430 Mg·m-3, m (MoK α)=0.984 mm-1, F (000)=1184.

Embodiment 5:

Two preparation to methyl-benzyl tin complex of salicyloyl hydrazone of 2- carbonyl propionic acids:

2.000g (5.0mmol) two pairs of methyl-benzyl dichlorides are added in the 250mL three-necked flasks for having nitrogen to protect Tin, 0.790g (5.2mmol) salicylyl hydrazine, 0.616g (5.6mmol) Sodium Pyruvates and 150mL solvent absolute methanols, in temperature Spend to react 22 h under conditions of 45 ~ 65 DEG C, cool down, filtering, solvent volatilization crystallization is controlled under conditions of 20 ~ 35 DEG C, obtains nothing Color transparent crystal, as 2- carbonyl propionic acids salicyloyl hydrazone two are to methyl-benzyl tin complex.Yield:74.6%.Fusing point:82~84℃ (dec)。

Elementary analysis (C54H60N4O10Sn2):Calculated value:C 55.79, H 5.20, N 4.82;Measured value:C 55.84, H 5.26, N 4.89.

FT-IR (KBr, ν/cm-1): 3453, 3019, 2920, 2849, 1616, 1587, 1381, 1321, 1252, 592, 555, 505, 446。

UV-vis (DMSO), λ max (nm): 334。

1H NMR (400 MHz, CDCl3) δ(ppm): 11.22 (s, 1H), 8.10 (d, J = 7.6 Hz, 1H), 7.49-7.45 (t, J = 7.9 Hz, 1H), 7.01-6.95 (m, 2H), 6.84-6.75 (m, 8H), 3.50 (s, 3H), 3.31 (s, 4H), 2.18-2.12 (s, 6H), 1.91(s, 3H)。

13C NMR (100 MHz, CDCl3) δ(ppm): 175.49, 160.78, 150.96, 135.48, 134.48, 132.76, 130.30, 129.27, 129.00, 128.25, 118.89, 117.31, 115.53, 35.76, 20.74, 12.80。

Crystallographic data:Monoclinic system, space group P2 (1)/n, a=1.14663 (7) nm, b=1.23714 (7) Nm, c=1.92461 (12) nm, α=γ=90 °, β=98.6890 (10) °, Z=4, V=2.6988 (3) nm3, Dc= 1.430 Mg·m-3, m (MoK α)=0.984 mm-1, F (000)=1184.

Embodiment 6:

Two preparation to methyl-benzyl tin complex of salicyloyl hydrazone of 2- carbonyl propionic acids:

4.000g (10.0mmol) two pairs of methyl-benzyl dichlorides are added in the 250mL three-necked flasks for having nitrogen to protect Tin, 1.550g (10.2mmol) salicylyl hydrazine, 1.166g (10.6mmol) Sodium Pyruvates and 150mL solvent absolute methanols, Temperature reacts 24 h under conditions of being 45 ~ 65 DEG C, cools down, filtering, and solvent volatilization crystallization is controlled under conditions of 20 ~ 35 DEG C, is obtained Colourless transparent crystal, as 2- carbonyl propionic acids salicyloyl hydrazone two are to methyl-benzyl tin complex.Yield:72.1%.Fusing point:82~84 ℃(dec)。

Elementary analysis (C54H60N4O10Sn2):Calculated value:C 55.79, H 5.20, N 4.82;Measured value:C 55.84, H 5.26, N 4.89.

FT-IR (KBr, ν/cm-1): 3453, 3019, 2920, 2849, 1616, 1587, 1381, 1321, 1252, 592, 555, 505, 446。

UV-vis (DMSO), λ max (nm): 334。

1H NMR (400 MHz, CDCl3) δ(ppm): 11.22 (s, 1H), 8.10 (d, J = 7.6 Hz, 1H), 7.49-7.45 (t, J = 7.9 Hz, 1H), 7.01-6.95 (m, 2H), 6.84-6.75 (m, 8H), 3.50 (s, 3H), 3.31 (s, 4H), 2.18-2.12 (s, 6H), 1.91(s, 3H)。

13C NMR (100 MHz, CDCl3) δ(ppm): 175.49, 160.78, 150.96, 135.48, 134.48, 132.76, 130.30, 129.27, 129.00, 128.25, 118.89, 117.31, 115.53, 35.76, 20.74, 12.80。

Crystallographic data:Monoclinic system, space group P2 (1)/n, a=1.14663 (7) nm, b=1.23714 (7) Nm, c=1.92461 (12) nm, α=γ=90 °, β=98.6890 (10) °, Z=4, V=2.6988 (3) nm3, Dc= 1.430 Mg·m-3, m (MoK α)=0.984 mm-1, F (000)=1184.

Test example:

For the 2- carbonyl propionic acids salicyloyl hydrazone two of the present invention to methyl-benzyl tin complex, its Anticancer Activity in vitro measure is logical Cross the realization of MTT experiment method.

MTT analytic approach:

3- (4,5-Dimethylthiazol-2-yl) -2,5-diphenyltetrazolium is reduced 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)(DMSO)Cell can be dissolved In first a ceremonial jade-ladle, used in libation, with ELIASA determine characteristic wavelength optical density, living cells quantity can be reflected indirectly.

The 2- carbonyl propionic acids salicyloyl hydrazone two of the preparation of embodiment 1 is determined to methyl-benzyl tin complex pair 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 line and cultivating system:Colo205, HepG2, MCF7, Hela and NCI-H460 cell line are derived from American. tissue Incubator(ATCC).With the RPMI 1640 containing 10% hyclone(GIBICO companies)Culture medium, 5%(Volume fraction)CO2、 In vitro culture is carried out in 37 DEG C of saturated humidity incubators.

Test process:Decoction will be tested(0.1ng/mL~10ug/mL)Concentration gradient according to concentration is added separately to 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 concentrations), control group (Only add nutrient solution and cell, be not added with testing medicine)And blank group(Only plus medicine is cultivated, be not added with cell and test medicine).After dosing Orifice plate is placed in 37 DEG C, 5%CO272h is cultivated in incubator.The activity of control drug determines according to the method for test sample.Cultivating In orifice plate after 72h, add MTT 40uL per hole(4mg/mL is made into D-Hanks buffer solutions).After 37 DEG C are placed 4h, remove Supernatant liquor.Add 150uL DMSO per hole, vibrate 5min, make Formazan crystallization dissolvings.Finally, existed using automatic ELIASA The optical density in each hole is detected at 570nm wavelength.

Data processing:Data processing uses the programs of Graph Pad Prism version 5.0, complex IC50Pass through journey The nonlinear regression model (NLRM) with S-shaped dose response is fitted to obtain in sequence.

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 line is analyzed, and determines its IC50Value, As a result as shown in table 1, conclusion is:From data in table, with the 2- carbonyl propionic acids salicyloyl hydrazone two of the present invention to methyl-benzyl Tin complex is used as cancer therapy 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 thing.

The 2- carbonyl propionic acids salicyloyl hydrazone two of table 1 is to methyl-benzyl tin complex cancer therapy drug external activity test data.

2- carbonyl propionic acids salicyloyl hydrazone two prepared by remaining embodiment is to methyl-benzyl tin complex with mtt assay to people's colon Cancer cell(Colo205), human liver cancer cell(HepG2), human breast cancer cell(MCF7), human cervical carcinoma cell(Hela)And people Lung carcinoma cell(NCI-H460)The same test example of active anticancer method of testing, test result and table 1 are essentially identical.

Claims (7)

1. a kind of 2- carbonyl propionic acids salicyloyl hydrazone two is to methyl-benzyl tin complex, for the complex of following structure formula (I):
(I)
Wherein R is to methyl-benzyl;Described complex (I) is crystal structure, and its crystallographic data is as follows:Monoclinic system, it is empty Between group P2 (1)/n, a=1.14663 (7) nm, b=1.23714 (7) nm, c=1.92461 (12) nm, α=γ= 90 °, β=98.6890 (10) °, Z=4, V=2.6988 (3) nm3, the Mgm of Dc=1.430-3, m (MoK α)=0.984 mm-1, F (000)=1184;Tin atom is seven coordination distortion pentagonal bipyramid configurations in molecule;Its ir data:FT-IR (KBr, ν/cm-1): 3453, 3019, 2920, 2849, 1616, 1587, 1381, 1321, 1252, 592, 555, 505, 446;Its ultraviolet-visible light modal data:UV-vis (DMSO),λ max(nm): 334;Its nuclear-magnetism modal data:1H NMR (400 MHz, CDCl3) δ(ppm): 11.22 (s, 1H), 8.10 (d, J = 7.6 Hz, 1H), 7.49-7.45 (t, J = 7.9 Hz, 1H), 7.01-6.95 (m, 2H), 6.84-6.75 (m, 8H), 3.50 (s, 3H), 3.31 (s, 4H), 2.18-2.12 (s, 6H), 1.91(s, 3H);13C NMR (100 MHz, CDCl3) δ(ppm): 175.49, 160.78, 150.96, 135.48, 134.48, 132.76, 130.30, 129.27, 129.00, 128.25, 118.89, 117.31, 115.53, 35.76, 20.74, 12.80;Described complex (I) is below 82 DEG C It can be stabilized.
2. the 2- carbonyl propionic acids salicyloyl hydrazone two described in claim 1 is to the preparation method of methyl-benzyl tin complex, its feature Be added in the reaction vessel for thering is nitrogen to protect two pairs of methyl-benzyl stannous chloride, salicylyl hydrazine, Sodium Pyruvate and solvent without Water methanol, 5 ~ 24 h are reacted under conditions of being 45 ~ 65 DEG C in temperature, cools down, filtering, solvent is controlled under conditions of 20 ~ 35 DEG C Volatilization crystallization, obtains colourless transparent crystal, as 2- carbonyl propionic acids salicyloyl hydrazone two is to methyl-benzyl tin complex.
3. the method prepared as claimed in claim 2, it is characterised in that two pairs of methyl-benzyl stannous chloride, salicyloyls Hydrazine, Sodium Pyruvate three material amount ratio be 1:(1~1.05):(1.05~1.15).
4. the method prepared as claimed in claim 2, it is characterised in that the solvent absolute methanol dosage is every mM two 15 ~ 35 milliliters are added to methyl-benzyl stannous chloride.
5. the method prepared as claimed in claim 2, it is characterised in that prepared using one kettle way.
6. the answering in cancer therapy drug is prepared to methyl-benzyl tin complex of 2- carbonyl propionic acids salicyloyl hydrazone two described in claim 1 With.
7. the application described in claim 6, wherein the cancer cell is that human colon cancer cell, human liver cancer cell, human breast carcinoma are thin Born of the same parents, human cervical carcinoma cell, human lung carcinoma cell.
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