CN105237563A - 2-oxo propionic acid p-hydroxy benzoyl hydrazone bis(2,4-dichlorobenzyl) tin complex and preparation method and application thereof - Google Patents

2-oxo propionic acid p-hydroxy benzoyl hydrazone bis(2,4-dichlorobenzyl) tin complex and preparation method and application thereof Download PDF

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CN105237563A
CN105237563A CN201510764228.2A CN201510764228A CN105237563A CN 105237563 A CN105237563 A CN 105237563A CN 201510764228 A CN201510764228 A CN 201510764228A CN 105237563 A CN105237563 A CN 105237563A
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propionic acid
dichloro benzyl
para hydroxybenzene
title complex
tin
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CN105237563B (en
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蒋伍玖
冯泳兰
谭宇星
朱小明
庾江喜
邝代治
张复兴
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衡阳师范学院
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Abstract

The invention discloses a 2-oxo propionic acid p-hydroxy benzoyl hydrazone bis(2,4-dichlorobenzyl) tin complex with the structural formula (I) (please see the formula in the specification), and R represents 2,4-dichlorobenzyl. The invention further discloses a preparation method of the 2-oxo propionic acid p-hydroxy benzoyl hydrazone bis(2,4-dichlorobenzyl) tin complex, and application of the 2-oxo propionic acid p-hydroxy benzoyl hydrazone bis(2,4-dichlorobenzyl) tin complex to anti-cancer medicine.

Description

A kind of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex and its preparation method and application

Technical field

The present invention relates to a kind of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex and preparation method thereof, and this 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex is preparing the application in cancer therapy drug.

Background technology

Organotin is the organometallics that a class contains Sn-C key.Researcher just noticed the Anticancer Activity in vitro of organo-tin compound before very early.1972, Brown Late Cambrian Ph 3snOOCCH 3inhibited to the growth of mouse cancer cells.1980, the research of the chemists such as Crowe showed, many organo-tin compounds have anti tumor activity in vitro.1989, American National anticancer research institute (NationalCancerInstitute) has carried out antitumor activity screening to more than 2,000 kinds of organo-tin compounds, and result shows that some organo-tin compounds have restraining effect to P388 Lymphocytic leukemia.2002, the people such as Gielen were doing comprehensive summing up to the activity of organotin carboxylate's ester cpds, thought that many organo-tin compounds have good Anticancer Activity in vitro really after research.

Research shows, the part of the organic group that organotin atom connects and participation coordination decides the biological activity of organo-tin compound, selects the tin atom coordination in some organic ligands with good biological activity itself and organotin to cause the great interest of people.Acylhydrazone is by a class Schiff compound of hydrazide kind compound modification, they are formed by aldehydes or ketones and hydrazides condensation, there is good biological activity, stronger coordination ability and various coordination mode, and have a wide range of applications in medicine, agricultural chemicals, material and analytical reagent etc.In recent years, domestic and international many researchists compare it and in depth study in biological activity, and research finds that acylhydrazone has the various active such as anticancer, sterilization, anti-inflammatory.Therefore, acylhydrazone class Schiff part is combined with organotin, attempts to obtain the stronger new compound of biological activity, become the interested research direction of people.

Chinese patent CN102718794A discloses a kind of pair of acylhydrazone class Schiff tin diphenyl title complex and the application in the medicine preparing anti-lung gland cancer, colorectal carcinoma, leukemia cell thereof.

Chinese patent CN101851251A discloses a kind of dibutyl tin title complex of acylhydrazone class Schiff part and is preparing the application in Hepatoma therapy, adenocarcinoma of lung, mammary cancer, prostate cancer, colorectal carcinoma or the leukemic medicine of young grain morning.

Document (JournalofOrganometallicChemistry, 2014,75:83-91) report, organotin acylhydrazone class Schiff base complex has comparatively strong biological activity to human colon cancer cell (HCT-116), human lung adenocarcinoma cell (A549), Human umbilical vein endothelial cells (HUVEC), and is better than carboplatin.

Document (JournalofOrganometallicChemistry, 2013,724:23-31) report, serial organotin acylhydrazone class Schiff base complex, organo-tin compound and acylhydrazone class Schiff part are respectively to the restraining effect of the cancer cells such as human lung adenocarcinoma cell (A549), human colon cancer cell (HCT-8), people in loop (hl-60).

Document (Bioorganic & MedicinalChemistryLetters, 2015,25:4461-4463) is reported, multiple acylhydrazone class Schiff part is to the antitumour activity of human liver cancer cell (HuH-7) and human lung adenocarcinoma cell (A549).

The experiment proved that the material with antitumour activity based on acylhydrazone class Schiff organotin complex, the present invention selects para hydroxybenzene formyl hydrazine, Sodium.alpha.-ketopropionate and two (2,4-dichloro benzyl) tindichloride reacts under certain condition, synthesis obtains title complex human colon cancer cell (Colo205), human liver cancer cell (HepG2), breast cancer cell (MCF7), cervical cancer cell (Hela) and human lung carcinoma cell (NCI-H460) to certain inhibit activities, for exploitation cancer therapy drug provides new approach.

Summary of the invention

The first object of the present invention there is provided a kind of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex.

The second object of the present invention is to provide above-mentioned 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin complex preparation method.

The third object of the present invention is to provide above-mentioned 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex and is preparing the application in cancer therapy drug.

As a kind of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex of a first aspect of the present invention, it is the title complex of structural formula (I)

(I)

Wherein R is 2,4-dichloro benzyl.

2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex of the present invention is through ultimate analysis, infrared spectra, nuclear magnetic resonance spectrum and the structural analysis of X-ray single crystal diffraction, and result is as follows:

Ultimate analysis (C 25h 22cl 4n 2o 5sn): calculated value: C43.46, H3.21, N4.05; Measured value: C43.54, H3.26, N4.02.

FT-IR(KBr,ν/cm -1):3633,3257,3194,2939,1606,1473,1392,1317,1286,1213,1168,761,638,592,538,509,468,445。

1HNMR(400MHz,DMSO- d 6)δ(ppm):9.98(s,1H),7.55(d, J=7.0Hz,2H),6.98(s,1H),6.74-6.82(m,4H),7.62(d, J=7.6Hz,2H),3.90(s,1H),3.29(s,3H),2.82-2.89(dt, J 1=8.8Hz, J 2=11.3Hz,4H),1.80(s,3H)。

13CNMR(100MHz,DMSO- d 6)δ(ppm):177.94,169.93,167.22,166.92,166.63,165.85,155.94,141.35,137.84,134.95,134.58,132.59,131.02,129.90,119.51,53.65,34.72,34.51,34.09,33.87,33.67.16.95。

2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2 of the present invention, 4-dichloro benzyl) tin title complex is crystalline structure, its crystal is oblique system, spacer P2 (1)/c, a=1.4900 (3) nm, b=0.87334 (19) nm, c=2.1418 (5) nm, α=γ=90 °, β=98.582 (3) °, Z=4, V=2.7559 (10) nm 3, Dc=1.665Mgm -3, m (MoK α)=1.353mm -1, F (000)=1376.

The constructional feature of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex of the present invention is: in molecule, tin atom is hexa-coordinate distorted octahedron configuration.

As a kind of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2 of a second aspect of the present invention; 4-dichloro benzyl) preparation method of tin title complex; two (2 are added in the reaction vessel having nitrogen protection; 4-dichloro benzyl) tindichloride, para hydroxybenzene formyl hydrazine, Sodium.alpha.-ketopropionate and solvent anhydrous methanol; be react 5 ~ 24h under the condition of 45 ~ 65 DEG C in temperature; cooling; filter; solvent evaporates crystallization is controlled under the condition of 20 ~ 35 DEG C; obtain reddish-brown transparent crystals; be 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex.

In a preferred embodiment of the invention, the amount of substance of described two (2,4-dichloro benzyl) tindichloride, para hydroxybenzene formyl hydrazine, Sodium.alpha.-ketopropionate three is than being 1:(1 ~ 1.05): (1.05 ~ 1.15).

In a preferred embodiment of the invention, described solvent anhydrous methanol consumption is that every mmole two (2,4-dichloro benzyl) tindichloride adds 15 ~ 35 milliliters.

2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2 of the present invention, 4-dichloro benzyl) tin complex preparation method is one kettle way, direct reaction in reactor is added together by whole raw material, without the separation of intermediate, directly prepare 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex.And the customary preparation methods of this area is for first to prepare part, again part and metallic starting compound are reacted and prepare title complex, 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2 of the present invention, 4-dichloro benzyl) tin complex preparation method compares this area customary preparation methods, there is the last handling process saving intermediate steps, save the advantages such as a large amount of human and material resources, financial resources.

A kind of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex as a third aspect of the present invention is preparing the application in cancer therapy drug.

Applicant is to above-mentioned 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex carried out anti tumor activity in vitro determine research, confirm 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex has certain anticancer bioactive, that is the purposes of above-mentioned title complex is preparing the application in cancer therapy drug, is exactly the application in the anti-human colorectal carcinoma of preparation, people's liver cancer, human breast carcinoma, human cervical carcinoma, people's lung-cancer medicament specifically.

2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2 of the present invention, 4-dichloro benzyl) tin title complex demonstrates good antitumour activity to human colon cancer cell, human liver cancer cell, human breast cancer cell, human cervical carcinoma cell, human lung carcinoma cell etc., 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2 of the present invention, 4-dichloro benzyl) feature such as tin title complex antitumour activity is high, cost is low, preparation method is simple, provide new way for developing new cancer therapy drug.

Accompanying drawing explanation

Fig. 1 is the IR spectrogram of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex.

Fig. 2 is 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex 1hNMR spectrogram.

Fig. 3 is 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex 13cNMR spectrogram.

Fig. 4 is the crystalline structure figure of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex.

Fig. 5 is the TG-DTG curve of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex.

Embodiment

Further describe the present invention by following examples, but scope of the present invention should be noted not by any restriction of these embodiments.

Embodiment 1:

The preparation of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex:

0.510g (1.0mmol) two (2 is added in the 100mL there-necked flask having nitrogen protection; 4-dichloro benzyl) tindichloride, 0.152g (1.0mmol) para hydroxybenzene formyl hydrazine, 0.121g (1.1mmol) Sodium.alpha.-ketopropionate and 25mL solvent anhydrous methanol; be react 8h under the condition of 45 ~ 65 DEG C in temperature; cooling; filter; solvent evaporates crystallization is controlled under the condition of 20 ~ 35 DEG C; obtain reddish-brown transparent crystals; be 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex.Productive rate: 66.8%.Fusing point: 149 ~ 150 DEG C (dec).

Ultimate analysis (C 25h 22cl 4n 2o 5sn): calculated value: C43.46, H3.21, N4.05; Measured value: C43.54, H3.26, N4.02.

FT-IR(KBr,ν/cm -1):3633,3257,3194,2939,1606,1473,1392,1317,1286,1213,1168,761,638,592,538,509,468,445。

1HNMR(400MHz,DMSO- d 6)δ(ppm):9.98(s,1H),7.55(d, J=7.0Hz,2H),6.98(s,1H),6.74-6.82(m,4H),7.62(d, J=7.6Hz,2H),3.90(s,1H),3.29(s,3H),2.82-2.89(dt, J 1=8.8Hz, J 2=11.3Hz,4H),1.80(s,3H)。

13CNMR(100MHz,DMSO- d 6)δ(ppm):177.94,169.93,167.22,166.92,166.63,165.85,155.94,141.35,137.84,134.95,134.58,132.59,131.02,129.90,119.51,53.65,34.72,34.51,34.09,33.87,33.67.16.95。

Crystallographic data: oblique system, spacer P2 (1)/c, a=1.4900 (3) nm, b=0.87334 (19) nm, c=2.1418 (5) nm, α=γ=90 °, β=98.582 (3) °, Z=4, V=2.7559 (10) nm 3, Dc=1.665Mgm -3, m (MoK α)=1.353mm -1, F (000)=1376.

Embodiment 2:

The preparation of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex:

0.510g (1.0mmol) two (2 is added in the 100mL there-necked flask having nitrogen protection; 4-dichloro benzyl) tindichloride, 0.152g (1.0mmol) para hydroxybenzene formyl hydrazine, 0.116g (1.05mmol) Sodium.alpha.-ketopropionate and 35mL solvent anhydrous methanol; be react 5h under the condition of 45 ~ 65 DEG C in temperature; cooling; filter; solvent evaporates crystallization is controlled under the condition of 20 ~ 35 DEG C; obtain reddish-brown transparent crystals; be 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex.Productive rate: 70.4%.Fusing point: 149 ~ 150 DEG C (dec).

Ultimate analysis (C 25h 22cl 4n 2o 5sn): calculated value: C43.46, H3.21, N4.05; Measured value: C43.54, H3.26, N4.02.

FT-IR(KBr,ν/cm -1):3633,3257,3194,2939,1606,1473,1392,1317,1286,1213,1168,761,638,592,538,509,468,445。

1HNMR(400MHz,DMSO- d 6)δ(ppm):9.98(s,1H),7.55(d, J=7.0Hz,2H),6.98(s,1H),6.74-6.82(m,4H),7.62(d, J=7.6Hz,2H),3.90(s,1H),3.29(s,3H),2.82-2.89(dt, J 1=8.8Hz, J 2=11.3Hz,4H),1.80(s,3H)。

13CNMR(100MHz,DMSO- d 6)δ(ppm):177.94,169.93,167.22,166.92,166.63,165.85,155.94,141.35,137.84,134.95,134.58,132.59,131.02,129.90,119.51,53.65,34.72,34.51,34.09,33.87,33.67.16.95。

Crystallographic data: oblique system, spacer P2 (1)/c, a=1.4900 (3) nm, b=0.87334 (19) nm, c=2.1418 (5) nm, α=γ=90 °, β=98.582 (3) °, Z=4, V=2.7559 (10) nm 3, Dc=1.665Mgm -3, m (MoK α)=1.353mm -1, F (000)=1376.

Embodiment 3:

The preparation of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex:

0.510g (1.0mmol) two (2 is added in the 100mL there-necked flask having nitrogen protection; 4-dichloro benzyl) tindichloride, 0.160g (1.05mmol) para hydroxybenzene formyl hydrazine, 0.127g (1.15mmol) Sodium.alpha.-ketopropionate and 30mL solvent anhydrous methanol; be react 15h under the condition of 45 ~ 65 DEG C in temperature; cooling; filter; solvent evaporates crystallization is controlled under the condition of 20 ~ 35 DEG C; obtain reddish-brown transparent crystals; be 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex.Productive rate: 69.9%.Fusing point: 149 ~ 150 DEG C (dec).

Ultimate analysis (C 25h 22cl 4n 2o 5sn): calculated value: C43.46, H3.21, N4.05; Measured value: C43.54, H3.26, N4.02.

FT-IR(KBr,ν/cm -1):3633,3257,3194,2939,1606,1473,1392,1317,1286,1213,1168,761,638,592,538,509,468,445。

1HNMR(400MHz,DMSO- d 6)δ(ppm):9.98(s,1H),7.55(d, J=7.0Hz,2H),6.98(s,1H),6.74-6.82(m,4H),7.62(d, J=7.6Hz,2H),3.90(s,1H),3.29(s,3H),2.82-2.89(dt, J 1=8.8Hz, J 2=11.3Hz,4H),1.80(s,3H)。

13CNMR(100MHz,DMSO- d 6)δ(ppm):177.94,169.93,167.22,166.92,166.63,165.85,155.94,141.35,137.84,134.95,134.58,132.59,131.02,129.90,119.51,53.65,34.72,34.51,34.09,33.87,33.67.16.95。

Crystallographic data: oblique system, spacer P2 (1)/c, a=1.4900 (3) nm, b=0.87334 (19) nm, c=2.1418 (5) nm, α=γ=90 °, β=98.582 (3) °, Z=4, V=2.7559 (10) nm 3, Dc=1.665Mgm -3, m (MoK α)=1.353mm -1, F (000)=1376.

Embodiment 4:

The preparation of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex:

2.550g (5.0mmol) two (2 is added in the 250mL there-necked flask having nitrogen protection; 4-dichloro benzyl) tindichloride, 0.775g (5.1mmol) para hydroxybenzene formyl hydrazine, 0.594g (5.4mmol) Sodium.alpha.-ketopropionate and 100mL solvent anhydrous methanol; be react 20h under the condition of 45 ~ 65 DEG C in temperature; cooling; filter; solvent evaporates crystallization is controlled under the condition of 20 ~ 35 DEG C; obtain reddish-brown transparent crystals; be 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex.Productive rate: 68.4%.Fusing point: 149 ~ 150 DEG C (dec).

Ultimate analysis (C 25h 22cl 4n 2o 5sn): calculated value: C43.46, H3.21, N4.05; Measured value: C43.54, H3.26, N4.02.

FT-IR(KBr,ν/cm -1):3633,3257,3194,2939,1606,1473,1392,1317,1286,1213,1168,761,638,592,538,509,468,445。

1HNMR(400MHz,DMSO- d 6)δ(ppm):9.98(s,1H),7.55(d, J=7.0Hz,2H),6.98(s,1H),6.74-6.82(m,4H),7.62(d, J=7.6Hz,2H),3.90(s,1H),3.29(s,3H),2.82-2.89(dt, J 1=8.8Hz, J 2=11.3Hz,4H),1.80(s,3H)。

13CNMR(100MHz,DMSO- d 6)δ(ppm):177.94,169.93,167.22,166.92,166.63,165.85,155.94,141.35,137.84,134.95,134.58,132.59,131.02,129.90,119.51,53.65,34.72,34.51,34.09,33.87,33.67.16.95。

Crystallographic data: oblique system, spacer P2 (1)/c, a=1.4900 (3) nm, b=0.87334 (19) nm, c=2.1418 (5) nm, α=γ=90 °, β=98.582 (3) °, Z=4, V=2.7559 (10) nm 3, Dc=1.665Mgm -3, m (MoK α)=1.353mm -1, F (000)=1376.

Embodiment 5:

The preparation of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex:

2.550g (5.0mmol) two (2 is added in the 250mL there-necked flask having nitrogen protection; 4-dichloro benzyl) tindichloride, 0.790g (5.2mmol) para hydroxybenzene formyl hydrazine, 0.616g (5.6mmol) Sodium.alpha.-ketopropionate and 150mL solvent anhydrous methanol; be react 22h under the condition of 45 ~ 65 DEG C in temperature; cooling; filter; solvent evaporates crystallization is controlled under the condition of 20 ~ 35 DEG C; obtain reddish-brown transparent crystals; be 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex.Productive rate: 67.6%.Fusing point: 149 ~ 150 DEG C (dec).

Ultimate analysis (C 25h 22cl 4n 2o 5sn): calculated value: C43.46, H3.21, N4.05; Measured value: C43.54, H3.26, N4.02.

FT-IR(KBr,ν/cm -1):3633,3257,3194,2939,1606,1473,1392,1317,1286,1213,1168,761,638,592,538,509,468,445。

1HNMR(400MHz,DMSO- d 6)δ(ppm):9.98(s,1H),7.55(d, J=7.0Hz,2H),6.98(s,1H),6.74-6.82(m,4H),7.62(d, J=7.6Hz,2H),3.90(s,1H),3.29(s,3H),2.82-2.89(dt, J 1=8.8Hz, J 2=11.3Hz,4H),1.80(s,3H)。

13CNMR(100MHz,DMSO- d 6)δ(ppm):177.94,169.93,167.22,166.92,166.63,165.85,155.94,141.35,137.84,134.95,134.58,132.59,131.02,129.90,119.51,53.65,34.72,34.51,34.09,33.87,33.67.16.95。

Crystallographic data: oblique system, spacer P2 (1)/c, a=1.4900 (3) nm, b=0.87334 (19) nm, c=2.1418 (5) nm, α=γ=90 °, β=98.582 (3) °, Z=4, V=2.7559 (10) nm 3, Dc=1.665Mgm -3, m (MoK α)=1.353mm -1, F (000)=1376.

Embodiment 6:

The preparation of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex:

5.100g (10.0mmol) two (2 is added in the 250mL there-necked flask having nitrogen protection; 4-dichloro benzyl) tindichloride, 1.550g (10.2mmol) para hydroxybenzene formyl hydrazine, 1.166g (10.6mmol) Sodium.alpha.-ketopropionate and 150mL solvent anhydrous methanol; be react 24h under the condition of 45 ~ 65 DEG C in temperature; cooling; filter; solvent evaporates crystallization is controlled under the condition of 20 ~ 35 DEG C; obtain reddish-brown transparent crystals; be 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex.Productive rate: 66.2%.Fusing point: 149 ~ 150 DEG C (dec).

Ultimate analysis (C 25h 22cl 4n 2o 5sn): calculated value: C43.46, H3.21, N4.05; Measured value: C43.54, H3.26, N4.02.

FT-IR(KBr,ν/cm -1):3633,3257,3194,2939,1606,1473,1392,1317,1286,1213,1168,761,638,592,538,509,468,445。

1HNMR(400MHz,DMSO- d 6)δ(ppm):9.98(s,1H),7.55(d, J=7.0Hz,2H),6.98(s,1H),6.74-6.82(m,4H),7.62(d, J=7.6Hz,2H),3.90(s,1H),3.29(s,3H),2.82-2.89(dt, J 1=8.8Hz, J 2=11.3Hz,4H),1.80(s,3H)。

13CNMR(100MHz,DMSO- d 6)δ(ppm):177.94,169.93,167.22,166.92,166.63,165.85,155.94,141.35,137.84,134.95,134.58,132.59,131.02,129.90,119.51,53.65,34.72,34.51,34.09,33.87,33.67.16.95。

Crystallographic data: oblique system, spacer P2 (1)/c, a=1.4900 (3) nm, b=0.87334 (19) nm, c=2.1418 (5) nm, α=γ=90 °, β=98.582 (3) °, Z=4, V=2.7559 (10) nm 3, Dc=1.665Mgm -3, m (MoK α)=1.353mm -1, F (000)=1376.

Test example:

2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex of the present invention, its Anticancer Activity in vitro is measured and is realized by MTT experiment method.

MTT analytical method:

Based on metabolism reduction 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide.Succinodehydrogenase in viable cell plastosome can make exogenous MTT be reduced to water-insoluble bluish voilet crystallization first a ceremonial jade-ladle, used in libation (Formazan) and be deposited in cell, and dead cell is without this function.First a ceremonial jade-ladle, used in libation in dimethyl sulfoxide (DMSO) (DMSO) energy dissolved cell, measures the optical density(OD) of characteristic wavelength, can indirectly reflect viable cell quantity by microplate reader.

Mtt assay is adopted to measure 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) the tin title complex of embodiment 1 preparation to the inhibit activities of 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 and culture system: Colo205, HepG2, MCF7, Hela and NCI-H460 cell strain takes from American. tissue incubator (ATCC).RPMI1640(GIBICO company with containing 10% foetal calf serum) substratum, in 5%(volume fraction) CO 2, carry out vitro culture in 37 DEG C of saturated humidity incubators.

Test process: join in each hole respectively by testing the concentration gradient of liquid (0.1ng/mL ~ 10ug/mL) according to concentration, each concentration establishes 6 parallel holes.Experiment is divided into drug study group (adding the test medicine of different concns respectively), control group (only add nutrient solution and cell, do not add test medicine) and blank group (only add cultivation medicine, do not add cell and test medicine).Orifice plate after dosing is placed in 37 DEG C, 5%CO 272h is cultivated in incubator.The activity of control drug measures according to the method for test sample.In orifice plate after having cultivated 72h, every hole adds MTT40uL(D-Hanks damping fluid and is made into 4mg/mL).After placing 4h at 37 DEG C, remove supernatant liquid.Every hole adds 150uLDMSO, and vibration 5min, makes Formazan dissolving crystallized.Finally, automatic microplate reader is utilized to detect the optical density(OD) in each hole at 570nm wavelength place.

Data processing: data processing uses GraphPadPrismversion5.0 program, title complex IC 50carry out matching by the nonlinear regression model (NLRM) in program with S shape dose response to obtain.

With MTT analytical method, 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 are analyzed, measure its IC 50value, result is as shown in table 1, conclusion is: from data in table, with 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2 of the present invention, 4-dichloro benzyl) tin title complex be 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), there is certain drug effect, can be used as the candidate compound of cancer therapy drug.

Table 12-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex cancer therapy drug external activity test data.

2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2 prepared by all the other embodiments, 4-dichloro benzyl) tin title complex is with the antitumour activity testing method same test example of mtt assay 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), and test result and table 1 are substantially identical.

Claims (10)

1. 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2, a 4-dichloro benzyl) tin title complex, the title complex for following structural formula (I):
(I)
Wherein R is 2,4-dichloro benzyl.
2. as claimed in claim 1 containing a kind of 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex, its ir data: FT-IR (KBr, ν/cm -1): 3633,3257,3194,2939,1606,1473,1392,1317,1286,1213,1168,761,638,592,538,509,468,445; Its nuclear-magnetism modal data: 1hNMR (400MHz, DMSO- d 6) δ (ppm): 9.98 (s, 1H), 7.55 (d, j=7.0Hz, 2H), 6.98 (s, 1H), 6.74-6.82 (m, 4H), 7.62 (d, j=7.6Hz, 2H), 3.90 (s, 1H), 3.29 (s, 3H), 2.82-2.89 (dt, j 1=8.8Hz, j 2=11.3Hz, 4H), 1.80 (s, 3H); 13cNMR (100MHz, DMSO- d 6) δ (ppm): 177.94,169.93,167.22,166.92,166.63,165.85,155.94,141.35,137.84,134.95,134.58,132.59,131.02,129.90,119.51,53.65,34.72,34.51,34.09,33.87,33.67.16.95.
3. 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2 as claimed in claim 1,4-dichloro benzyl) tin title complex, wherein, described 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex is crystalline structure, its crystallographic data is as follows: oblique system, spacer P2 (1)/c, a=1.4900 (3) nm, b=0.87334 (19) nm, c=2.1418 (5) nm, α=γ=90 °, β=98.582 (3) °, Z=4, V=2.7559 (10) nm 3, Dc=1.665Mgm -3, m (MoK α)=1.353mm -1, F (000)=1376; In molecule, tin atom is hexa-coordinate distorted octahedron configuration.
4. described in claim 1,2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex has certain thermally-stabilised scope, can stable existence below 149 DEG C.
5. 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2 according to claim 1; 4-dichloro benzyl) preparation method of tin title complex; it is characterized in that adding two (2 in the reaction vessel having nitrogen protection; 4-dichloro benzyl) tindichloride, para hydroxybenzene formyl hydrazine, Sodium.alpha.-ketopropionate and solvent anhydrous methanol; be react 5 ~ 24h under the condition of 45 ~ 65 DEG C in temperature; cooling; filter; solvent evaporates crystallization is controlled under the condition of 20 ~ 35 DEG C; obtain reddish-brown transparent crystals; be 2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex.
6. the method for preparation as claimed in claim 5, it is characterized in that, the amount of substance of described two (2,4-dichloro benzyl) tindichloride, para hydroxybenzene formyl hydrazine, Sodium.alpha.-ketopropionate three is than being 1:(1 ~ 1.05): (1.05 ~ 1.15).
7. the method for preparation as claimed in claim 5, it is characterized in that, described solvent anhydrous methanol consumption is that every mmole two (2,4-dichloro benzyl) tindichloride adds 15 ~ 35 milliliters.
8. the method for preparation as claimed in claim 5, is characterized in that, adopts one kettle way preparation.
9. described in claim 1,2-carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4-dichloro benzyl) tin title complex is preparing the application in cancer therapy drug.
10. application according to claim 9, wherein said cancer cells is human colon cancer cell, human liver cancer cell, human breast cancer cell, human cervical carcinoma cell, human lung carcinoma cell.
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