CN105237564B - A kind of phenylpropionic acid salicyloyl hydrazone two of 2 carbonyl 3 is to methyl-benzyl tin complex and its preparation method and application - Google Patents

A kind of phenylpropionic acid salicyloyl hydrazone two of 2 carbonyl 3 is to methyl-benzyl tin complex and its preparation method and application Download PDF

Info

Publication number
CN105237564B
CN105237564B CN201510764229.7A CN201510764229A CN105237564B CN 105237564 B CN105237564 B CN 105237564B CN 201510764229 A CN201510764229 A CN 201510764229A CN 105237564 B CN105237564 B CN 105237564B
Authority
CN
China
Prior art keywords
methyl
benzyl
salicyloyl hydrazone
complex
1h
Prior art date
Application number
CN201510764229.7A
Other languages
Chinese (zh)
Other versions
CN105237564A (en
Inventor
蒋伍玖
朱小明
谭宇星
庾江喜
邝代治
冯泳兰
张复兴
Original Assignee
衡阳师范学院
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 衡阳师范学院 filed Critical 衡阳师范学院
Priority to CN201510764229.7A priority Critical patent/CN105237564B/en
Publication of CN105237564A publication Critical patent/CN105237564A/en
Application granted granted Critical
Publication of CN105237564B publication Critical patent/CN105237564B/en

Links

Abstract

The invention discloses a kind of phenylpropionic acid salicyloyl hydrazone two of 2 carbonyl 3 to methyl-benzyl tin complex, for the complex of following structure formula (I), wherein Ph is phenyl, and R is to methyl-benzyl.The invention also discloses the preparation method of the phenylpropionic acid salicyloyl hydrazone two of 2 carbonyl 3 to methyl-benzyl tin complex and the application in cancer therapy drug is prepared.

Description

A kind of 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two to methyl-benzyl tin complex and Its preparation method and application

Technical field

The present invention relates to a kind of 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two to methyl-benzyl tin complex and its preparation side Method, and 2- carbonyl -3- phenylpropionic acids two applications to methyl-benzyl tin complex in cancer therapy drug is prepared of salicyloyl hydrazone.

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.beta.-phenylpyruvate are reacted under certain condition with two pairs of methyl-benzyl stannous chloride, and synthesis has been obtained to people Colon cancer cell(Colo205), human liver cancer cell(HepG2), breast cancer cell(MCF7), cervical cancer cell(Hela)And people Lung carcinoma 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- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two and methyl-benzyl tin matched somebody with somebody Compound.

The second object of the present invention is to provide above-mentioned 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two and methyl-benzyl tin is coordinated Thing preparation method.

The third object of the present invention is to provide above-mentioned 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two and methyl-benzyl tin is coordinated Application of the thing in cancer therapy drug is prepared.

A kind of 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two as the first aspect of the present invention coordinates methyl-benzyl tin Thing, it is the complex of structure formula (I)

(I)

Wherein Ph is phenyl, and R is to methyl-benzyl.

2- carbonyl -3- phenylpropionic acids the salicyloyl hydrazone two of the present invention is to methyl-benzyl tin complex through elementary analysis, infrared Spectrum, nuclear magnetic resoance spectrum and X-ray single crystal diffraction structural analysis, it is as a result as follows:

Elementary analysis (C66H68N4O10Sn2):Calculated value:C 60.30, H 5.21, N 4.26;Measured value:C 60.34, H 5.26, N 4.29.

FT-IR (KBr, ν/cm-1): 3452, 3022, 2918, 1614, 1607, 1587, 1381, 1325, 1248, 590, 563, 507, 457。

1H NMR (400 MHz, DMSO-d 6) δ(ppm): 12.15 (s, 1H), 7.84 (d, J = 6.0 Hz, 1H), 7.36(s, 1H), 7.09-7.20 (m, 3H), 7.00-6.81 (m, 4H), 6.55 (s, 8H), 4.05 (s, 1H), 3.28 (s, 2H), 3.18 (s, 3H), 2.79 (s, 4H), 2.04 (s, 6H)。

13C NMR (100 MHz, DMSO-d 6) δ(ppm): 172.89, 164.13, 150.76, 135.16, 135.00, 132.76, 132.60, 128.44, 127.91, 127.83, 127.65, 125.84, 118.59, 117.97, 116.66, 116.40, 48.38, 37.86, 31.61, 20.26。

2- carbonyl -3- phenylpropionic acids the salicyloyl hydrazone two of the present invention is crystal structure to methyl-benzyl tin complex, and it is brilliant Body is monoclinic system, space group C2/c, a=3.0589 (3) nm, b=1.24621 (14) nm, c=1.7214 (2) nm, α=γ=90 °, β=105.503 (2) °, Z=4, V=6.3233 (12) nm3, the Mgm of Dc=1.381-3, m (MoK α)= 0.849 mm-1, F (000)=2688.

2- carbonyl -3- phenylpropionic acids the salicyloyl hydrazone two of the present invention is structurally characterized in that to methyl-benzyl tin complex:Point Tin atom is seven coordination distortion pentagonal bipyramid configurations in son.

A kind of 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two as the second aspect of the present invention coordinates methyl-benzyl tin The preparation method of thing, two pairs of methyl-benzyl stannous chloride, salicylyl hydrazine, propiophenones are added in the reaction vessel for having nitrogen to protect Sour sodium and solvent absolute methanol, 5 ~ 24 h are reacted under conditions of being 45 ~ 65 DEG C in temperature, are cooled down, filtering, in 20 ~ 35 DEG C of bar Solvent volatilization crystallization is controlled under part, obtains yellow transparent crystal, as 2- carbonyls -3- phenylpropionic 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, phenylpyruvic acids The amount ratio of the material of sodium 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.

2- carbonyl -3- phenylpropionic acids the salicyloyl hydrazone two of the present invention is one pot to methyl-benzyl tin complex preparation method Method, will whole raw materials add in reactor directly react together, without the separation of intermediate, be directly prepared 2- carbonyls- 3- phenylpropionic acids salicyloyl hydrazone two is to methyl-benzyl tin complex.And the customary preparation methods of this area are matched somebody with somebody to be first prepared Body, then complex, 2- carbonyl -3- phenylpropionic acid water of the invention is prepared in part and the starting compound reaction containing metal Poplar acylhydrazone two compares this area customary preparation methods to methyl-benzyl tin complex preparation method, has and saves intermediate steps Last handling process, the advantages that saving substantial amounts of human and material resources, financial resources.

A kind of 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two as the third aspect of the present invention coordinates methyl-benzyl tin Application of the thing in cancer therapy drug is prepared.

Applicant has carried out external anti-to above-mentioned 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two to methyl-benzyl tin complex Tumor promotion determines research, it is thus identified that 2- carbonyl -3- phenylpropionic acids salicyloyl hydrazone two has certain to methyl-benzyl tin complex Anticancer bioactive, that is to say, that the purposes of above-mentioned complex is the application in cancer therapy drug is prepared, and is exactly specifically Application in anti-human colon cancer, human liver cancer, human breast carcinoma, human cervical carcinoma, human lung cancer medicine is prepared.

The present invention 2- carbonyl -3- phenylpropionic acids salicyloyl hydrazone two to methyl-benzyl tin complex to human colon cancer cell, Human liver cancer cell, human breast cancer cell, human cervical carcinoma cell, human lung carcinoma cell etc. show good active anticancer, this hair Bright 2- carbonyl -3- phenylpropionic acids salicyloyl hydrazone two is to methyl-benzyl tin complex active anticancer is high, cost is low, preparation method is simple The features such as single, the cancer therapy drug to develop new provide new way.

Brief description of the drawings

Fig. 1 is IR spectrogram of the 2- carbonyl -3- phenylpropionic acids salicyloyl hydrazone two to methyl-benzyl tin complex.

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

Fig. 3 is 2- carbonyl -3- phenylpropionic acids salicyloyl hydrazone two to methyl-benzyl tin complex13C NMR spectras.

Fig. 4 is crystal structure figure of the 2- carbonyl -3- phenylpropionic acids salicyloyl hydrazone two to methyl-benzyl tin complex.

Fig. 5 is TG-DTG curve of the 2- carbonyl -3- phenylpropionic 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:

2- carbonyl -3- phenylpropionic acids two preparations to methyl-benzyl tin complex of salicyloyl hydrazone:

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, 0.205g (1.1mmol) Sodium.beta.-phenylpyruvates and 25mL solvent absolute methanols, in temperature Spend 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, obtains yellow Transparent crystal, as 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two is to methyl-benzyl tin complex.Yield:85.4%.Fusing point:90 ~91℃(dec)。

Elementary analysis (C66H68N4O10Sn2):Calculated value:C 60.30, H 5.21, N 4.26;Measured value:C 60.34, H 5.26, N 4.29.

FT-IR (KBr, ν/cm-1): 3452, 3022, 2918, 1614, 1607, 1587, 1381, 1325, 1248, 590, 563, 507, 457。

1H NMR (400 MHz, DMSO-d 6) δ(ppm): 12.15 (s, 1H), 7.84 (d, J = 6.0 Hz, 1H), 7.36(s, 1H), 7.09-7.20 (m, 3H), 7.00-6.81 (m, 4H), 6.55 (s, 8H), 4.05 (s, 1H), 3.28 (s, 2H), 3.18 (s, 3H), 2.79 (s, 4H), 2.04 (s, 6H)。

13C NMR (100 MHz, DMSO-d 6) δ(ppm): 172.89, 164.13, 150.76, 135.16, 135.00, 132.76, 132.60, 128.44, 127.91, 127.83, 127.65, 125.84, 118.59, 117.97, 116.66, 116.40, 48.38, 37.86, 31.61, 20.26。

Crystallographic data:Monoclinic system, space group C2/c, a=3.0589 (3) nm, b=1.24621 (14) nm, c =1.7214 (2) nm, α=γ=90 °, β=105.503 (2) °, Z=4, V=6.3233 (12) nm3, Dc=1.381 Mg·m-3, m (MoK α)=0.849 mm-1, F (000)=2688.

Embodiment 2:

2- carbonyl -3- phenylpropionic acids two preparations to methyl-benzyl tin complex of salicyloyl hydrazone:

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, 0.195g (1.05mmol) Sodium.beta.-phenylpyruvates and 35mL solvent absolute methanols, Temperature reacts 5 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 yellow Color transparent crystal, as 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two is to methyl-benzyl tin complex.Yield:87.3%.Fusing point: 90~91℃(dec)。

Elementary analysis (C66H68N4O10Sn2):Calculated value:C 60.30, H 5.21, N 4.26;Measured value:C 60.34, H 5.26, N 4.29.

FT-IR (KBr, ν/cm-1): 3452, 3022, 2918, 1614, 1607, 1587, 1381, 1325, 1248, 590, 563, 507, 457。

1H NMR (400 MHz, DMSO-d 6) δ(ppm): 12.15 (s, 1H), 7.84 (d, J = 6.0 Hz, 1H), 7.36(s, 1H), 7.09-7.20 (m, 3H), 7.00-6.81 (m, 4H), 6.55 (s, 8H), 4.05 (s, 1H), 3.28 (s, 2H), 3.18 (s, 3H), 2.79 (s, 4H), 2.04 (s, 6H)。

13C NMR (100 MHz, DMSO-d 6) δ(ppm): 172.89, 164.13, 150.76, 135.16, 135.00, 132.76, 132.60, 128.44, 127.91, 127.83, 127.65, 125.84, 118.59, 117.97, 116.66, 116.40, 48.38, 37.86, 31.61, 20.26。

Crystallographic data:Monoclinic system, space group C2/c, a=3.0589 (3) nm, b=1.24621 (14) nm, c =1.7214 (2) nm, α=γ=90 °, β=105.503 (2) °, Z=4, V=6.3233 (12) nm3, Dc=1.381 Mg·m-3, m (MoK α)=0.849 mm-1, F (000)=2688.

Embodiment 3:

2- carbonyl -3- phenylpropionic acids two preparations to methyl-benzyl tin complex of salicyloyl hydrazone:

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, 0.214g (1.15mmol) Sodium.beta.-phenylpyruvates and 30mL solvent absolute methanols, Temperature reacts 15 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 Yellow transparent crystal, as 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two is to methyl-benzyl tin complex.Yield:88.0%.It is molten Point:90~91℃(dec).

Elementary analysis (C66H68N4O10Sn2):Calculated value:C 60.30, H 5.21, N 4.26;Measured value:C 60.34, H 5.26, N 4.29.

FT-IR (KBr, ν/cm-1): 3452, 3022, 2918, 1614, 1607, 1587, 1381, 1325, 1248, 590, 563, 507, 457。

1H NMR (400 MHz, DMSO-d 6) δ(ppm): 12.15 (s, 1H), 7.84 (d, J = 6.0 Hz, 1H), 7.36(s, 1H), 7.09-7.20 (m, 3H), 7.00-6.81 (m, 4H), 6.55 (s, 8H), 4.05 (s, 1H), 3.28 (s, 2H), 3.18 (s, 3H), 2.79 (s, 4H), 2.04 (s, 6H)。

13C NMR (100 MHz, DMSO-d 6) δ(ppm): 172.89, 164.13, 150.76, 135.16, 135.00, 132.76, 132.60, 128.44, 127.91, 127.83, 127.65, 125.84, 118.59, 117.97, 116.66, 116.40, 48.38, 37.86, 31.61, 20.26。

Crystallographic data:Monoclinic system, space group C2/c, a=3.0589 (3) nm, b=1.24621 (14) nm, c =1.7214 (2) nm, α=γ=90 °, β=105.503 (2) °, Z=4, V=6.3233 (12) nm3, Dc=1.381 Mg·m-3, m (MoK α)=0.849 mm-1, F (000)=2688.

Embodiment 4:

2- carbonyl -3- phenylpropionic acids two preparations to methyl-benzyl tin complex of salicyloyl hydrazone:

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, 1.004g (5.4mmol) Sodium.beta.-phenylpyruvates and 100mL solvent absolute methanols, Temperature reacts 20 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 Yellow transparent crystal, as 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two is to methyl-benzyl tin complex.Yield:77.9%.It is molten Point:90~91℃(dec).

Elementary analysis (C66H68N4O10Sn2):Calculated value:C 60.30, H 5.21, N 4.26;Measured value:C 60.34, H 5.26, N 4.29.

FT-IR (KBr, ν/cm-1): 3452, 3022, 2918, 1614, 1607, 1587, 1381, 1325, 1248, 590, 563, 507, 457。

1H NMR (400 MHz, DMSO-d 6) δ(ppm): 12.15 (s, 1H), 7.84 (d, J = 6.0 Hz, 1H), 7.36(s, 1H), 7.09-7.20 (m, 3H), 7.00-6.81 (m, 4H), 6.55 (s, 8H), 4.05 (s, 1H), 3.28 (s, 2H), 3.18 (s, 3H), 2.79 (s, 4H), 2.04 (s, 6H)。

13C NMR (100 MHz, DMSO-d 6) δ(ppm): 172.89, 164.13, 150.76, 135.16, 135.00, 132.76, 132.60, 128.44, 127.91, 127.83, 127.65, 125.84, 118.59, 117.97, 116.66, 116.40, 48.38, 37.86, 31.61, 20.26。

Crystallographic data:Monoclinic system, space group C2/c, a=3.0589 (3) nm, b=1.24621 (14) nm, c =1.7214 (2) nm, α=γ=90 °, β=105.503 (2) °, Z=4, V=6.3233 (12) nm3, Dc=1.381 Mg·m-3, m (MoK α)=0.849 mm-1, F (000)=2688.

Embodiment 5:

2- carbonyl -3- phenylpropionic acids two preparations to methyl-benzyl tin complex of salicyloyl hydrazone:

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, 1.042g (5.6mmol) Sodium.beta.-phenylpyruvates and 150mL solvent absolute methanols, Temperature reacts 22 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 Yellow transparent crystal, as 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two is to methyl-benzyl tin complex.Yield:76.6%.It is molten Point:90~91℃(dec).

Elementary analysis (C66H68N4O10Sn2):Calculated value:C 60.30, H 5.21, N 4.26;Measured value:C 60.34, H 5.26, N 4.29.

FT-IR (KBr, ν/cm-1): 3452, 3022, 2918, 1614, 1607, 1587, 1381, 1325, 1248, 590, 563, 507, 457。

1H NMR (400 MHz, DMSO-d 6) δ(ppm): 12.15 (s, 1H), 7.84 (d, J = 6.0 Hz, 1H), 7.36(s, 1H), 7.09-7.20 (m, 3H), 7.00-6.81 (m, 4H), 6.55 (s, 8H), 4.05 (s, 1H), 3.28 (s, 2H), 3.18 (s, 3H), 2.79 (s, 4H), 2.04 (s, 6H)。

13C NMR (100 MHz, DMSO-d 6) δ(ppm): 172.89, 164.13, 150.76, 135.16, 135.00, 132.76, 132.60, 128.44, 127.91, 127.83, 127.65, 125.84, 118.59, 117.97, 116.66, 116.40, 48.38, 37.86, 31.61, 20.26。

Crystallographic data:Monoclinic system, space group C2/c, a=3.0589 (3) nm, b=1.24621 (14) nm, c =1.7214 (2) nm, α=γ=90 °, β=105.503 (2) °, Z=4, V=6.3233 (12) nm3, Dc=1.381 Mg·m-3, m (MoK α)=0.849 mm-1, F (000)=2688.

Embodiment 6:

2- carbonyl -3- phenylpropionic acids two preparations to methyl-benzyl tin complex of salicyloyl hydrazone:

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, 1.972g (10.6mmol) Sodium.beta.-phenylpyruvates and 150mL solvent absolute methanols, 24 h are reacted under conditions of being 45 ~ 65 DEG C in temperature, are cooled down, filtering, solvent volatilization crystallization is controlled under conditions of 20 ~ 35 DEG C, Yellow transparent crystal is obtained, as 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two is to methyl-benzyl tin complex.Yield:74.1%. Fusing point:90~91℃(dec).

Elementary analysis (C66H68N4O10Sn2):Calculated value:C 60.30, H 5.21, N 4.26;Measured value:C 60.34, H 5.26, N 4.29.

FT-IR (KBr, ν/cm-1): 3452, 3022, 2918, 1614, 1607, 1587, 1381, 1325, 1248, 590, 563, 507, 457。

1H NMR (400 MHz, DMSO-d 6) δ(ppm): 12.15 (s, 1H), 7.84 (d, J = 6.0 Hz, 1H), 7.36(s, 1H), 7.09-7.20 (m, 3H), 7.00-6.81 (m, 4H), 6.55 (s, 8H), 4.05 (s, 1H), 3.28 (s, 2H), 3.18 (s, 3H), 2.79 (s, 4H), 2.04 (s, 6H)。

13C NMR (100 MHz, DMSO-d 6) δ(ppm): 172.89, 164.13, 150.76, 135.16, 135.00, 132.76, 132.60, 128.44, 127.91, 127.83, 127.65, 125.84, 118.59, 117.97, 116.66, 116.40, 48.38, 37.86, 31.61, 20.26。

Crystallographic data:Monoclinic system, space group C2/c, a=3.0589 (3) nm, b=1.24621 (14) nm, c =1.7214 (2) nm, α=γ=90 °, β=105.503 (2) °, Z=4, V=6.3233 (12) nm3, Dc=1.381 Mg·m-3, m (MoK α)=0.849 mm-1, F (000)=2688.

Test example:

2- carbonyl -3- phenylpropionic acids the salicyloyl hydrazone two of the present invention is to methyl-benzyl tin complex, its Anticancer Activity in vitro Measure is realized by 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.

Methyl-benzyl tin is matched somebody with somebody to determine the 2- carbonyl -3- phenylpropionic acids salicyloyl hydrazone two of the preparation of embodiment 1 using mtt assay Compound is to human colon cancer cell(Colo205), human liver cancer cell(HepG2), human breast cancer cell(MCF7), human cervical carcinoma it is thin Born of the same parents(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 -3- phenylpropionic acids salicyloyl hydrazones two of the present invention to first Base benzyl tin complex is used as cancer therapy drug, to human colon cancer cell(Colo205), human liver cancer cell(HepG2), human breast carcinoma Cell(MCF7), human cervical carcinoma cell(Hela)And human lung carcinoma cell(NCI-H460)With certain drug effect, can be used as anti- The candidate compound of cancer drug.

2- carbonyl -3- phenylpropionic acids the salicyloyl hydrazone two of table 1 is to methyl-benzyl tin complex cancer therapy drug external activity test Data.

2- carbonyl -3- phenylpropionic acids salicyloyl hydrazone two prepared by remaining embodiment is to methyl-benzyl tin complex with 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)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- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two is to methyl-benzyl tin complex, for the cooperation of following structure formula (I) Thing:
(I)
Wherein Ph is phenyl, and R is to methyl-benzyl;Described complex (I) is crystal structure, and its crystallographic data is as follows:It is single Oblique system, space group C2/c, a=3.0589 (3) nm, b=1.24621 (14) nm, c=1.7214 (2) nm, α=γ =90 °, β=105.503 (2) °, Z=4, V=6.3233 (12) nm3, the Mgm of Dc=1.381-3, m (MoK α)=0.849 mm-1, F (000)=2688;Tin atom is seven coordination distortion pentagonal bipyramid configurations in molecule;Described complex (I) it is infrared Spectroscopic data:FT-IR (KBr, ν/cm-1): 3452, 3022, 2918, 1614, 1607, 1587, 1381, 1325, 1248, 590, 563, 507, 457;Nuclear-magnetism modal data:1H NMR (400 MHz, DMSO-d 6) δ(ppm): 12.15 (s, 1H), 7.84 (d, J = 6.0 Hz, 1H), 7.36(s, 1H), 7.09-7.20 (m, 3H), 7.00-6.81 (m, 4H), 6.55 (s, 8H), 4.05 (s, 1H), 3.28 (s, 2H), 3.18 (s, 3H), 2.79 (s, 4H), 2.04 (s, 6H);13C NMR (100 MHz, DMSO-d 6) δ(ppm): 172.89, 164.13, 150.76, 135.16, 135.00, 132.76, 132.60, 128.44, 127.91, 127.83, 127.65, 125.84, 118.59, 117.97, 116.66, 116.40, 48.38, 37.86, 31.61, 20.26;Described complex (I) tool There is certain thermostabilization scope, can be stabilized below 90 DEG C.
2. 2- carbonyl -3- phenylpropionic acids salicyloyl hydrazone two described in claim 1 is to the preparation method of methyl-benzyl tin complex, It is characterized in that two pairs of methyl-benzyl stannous chloride, salicylyl hydrazine, Sodium.beta.-phenylpyruvates are added in the reaction vessel for having nitrogen to protect And solvent absolute methanol, 5 ~ 24 h are reacted under conditions of being 45 ~ 65 DEG C in temperature, are cooled down, filtering, under conditions of 20 ~ 35 DEG C Solvent volatilization crystallization is controlled, obtains yellow transparent crystal, as 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two is matched somebody with somebody to methyl-benzyl tin Compound.
3. preparation method as claimed in claim 2, it is characterised in that two pairs of methyl-benzyl stannous chloride, salicylyl hydrazine, The amount ratio of the material of Sodium.beta.-phenylpyruvate three is 1:(1~1.05):(1.05~1.15).
4. preparation method as claimed in claim 2, it is characterised in that the solvent absolute methanol dosage is two pairs every mM Methyl-benzyl stannous chloride adds 15 ~ 35 milliliters.
5. preparation method as claimed in claim 2, it is characterised in that prepared using one kettle way.
6. 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone two is preparing anticarcinogen to methyl-benzyl tin complex described in claim 1 Application in thing.
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.
CN201510764229.7A 2015-11-11 2015-11-11 A kind of phenylpropionic acid salicyloyl hydrazone two of 2 carbonyl 3 is to methyl-benzyl tin complex and its preparation method and application CN105237564B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510764229.7A CN105237564B (en) 2015-11-11 2015-11-11 A kind of phenylpropionic acid salicyloyl hydrazone two of 2 carbonyl 3 is to methyl-benzyl tin complex and its preparation method and application

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510764229.7A CN105237564B (en) 2015-11-11 2015-11-11 A kind of phenylpropionic acid salicyloyl hydrazone two of 2 carbonyl 3 is to methyl-benzyl tin complex and its preparation method and application

Publications (2)

Publication Number Publication Date
CN105237564A CN105237564A (en) 2016-01-13
CN105237564B true CN105237564B (en) 2018-01-16

Family

ID=55035429

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510764229.7A CN105237564B (en) 2015-11-11 2015-11-11 A kind of phenylpropionic acid salicyloyl hydrazone two of 2 carbonyl 3 is to methyl-benzyl tin complex and its preparation method and application

Country Status (1)

Country Link
CN (1) CN105237564B (en)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105753896A (en) * 2016-04-11 2016-07-13 衡阳师范学院 2-carbonyl-3-phenylpropionic acid p-hydroxyphenylcarbonylhydrazone dibenzyl tin complex as well as preparation method and application thereof
CN105693763B (en) * 2016-04-22 2018-09-14 衡阳师范学院 A kind of organotin complex of the ligand containing acylhydrazone and its preparation method and application
CN105884818A (en) * 2016-04-22 2016-08-24 衡阳师范学院 2-carbonyl-3-phenylpropionic acid benzoyl hydrazone diphenyltin complex and preparation method and application thereof
CN105777799B (en) * 2016-04-22 2018-11-27 衡阳师范学院 A kind of benzoyl hydrazone Dibenzyltin complex and its preparation method and application
CN105859768A (en) * 2016-04-23 2016-08-17 衡阳师范学院 2-carbonyl-3-phenylpropionic acid salicylhydrazone dibenzyltin complex and preparation method and application thereof
CN105732698A (en) * 2016-04-23 2016-07-06 衡阳师范学院 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone bi(2,4-dichloro benzyl) tin complex and preparation method and application thereof
CN105693762A (en) * 2016-04-23 2016-06-22 衡阳师范学院 2-carbonyl-2-phenylacetic acid benzoylhydrazone di-n-butyltin tin complex and preparation method and application thereof
CN106279250B (en) * 2016-08-13 2018-11-27 衡阳师范学院 A kind of stannous phenide complex and its preparation method and application
CN106317103A (en) * 2016-08-13 2017-01-11 衡阳师范学院 2-carbonyl butyrate p-hydroxy benzoyl hydrazone di-n-butyltin complex and preparation method and application thereof
CN106279251A (en) * 2016-08-13 2017-01-04 衡阳师范学院 A kind of 2 carbonyl propionic acid benzoyl hydrazones two are to methyl-benzyl stannum coordination compound and its preparation method and application
CN106220668B (en) * 2016-08-20 2018-09-14 衡阳师范学院 A kind of 2- carbonyls -3- phenylpropionic acids salicyloyl hydrazone di-n-butyl tin complex and its preparation method and application
CN106279258B (en) * 2016-08-20 2018-09-14 衡阳师范学院 A kind of dialkyl tin complex and its preparation method and application
CN106366116A (en) * 2016-08-23 2017-02-01 衡阳师范学院 2-Oxo-3-phenylpropionic acid p-methylbenzoyl hydrazone di-p-methylbenzyltin complex, and preparation method and application thereof
CN106220670B (en) * 2016-08-23 2018-09-14 衡阳师范学院 Two pairs of methylbenzyl tin complexs of one kind and its preparation method and application
CN106220673A (en) * 2016-08-25 2016-12-14 衡阳师范学院 A kind of 2 carbonyl 2 phenylacetic acids are to toluyl hydrazone di-n-butyl tin coordination compound and its preparation method and application
CN106336426A (en) * 2016-08-25 2017-01-18 衡阳师范学院 2-carbonyl-2-phenyl acetic acid p-nitrobenzoylhydrazone bis(p-methylbenzyl)tin complex and preparation method and application thereof
CN106220674B (en) * 2016-08-26 2018-09-07 衡阳师范学院 A kind of Dibenzyltin complex and its preparation method and application
CN106478696B (en) * 2016-10-18 2018-04-03 四川理工学院 A kind of salicyloyl hydrazone Zn complex fluorescence probe and its preparation method and application

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102060869A (en) * 2010-12-14 2011-05-18 聊城大学 Tindiphenyl (IV) coordination compound of benzoylformic acid-3-hydroxyl-2-naphthyl formyl hydrazone as well as preparation method and application thereof

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101503423B (en) * 2008-11-17 2011-05-11 聊城大学 Parachlorobenzoyl hydrazone organotin complex, preparation and use

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102060869A (en) * 2010-12-14 2011-05-18 聊城大学 Tindiphenyl (IV) coordination compound of benzoylformic acid-3-hydroxyl-2-naphthyl formyl hydrazone as well as preparation method and application thereof

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
2-羰基丙酸(芳甲酰基)腙二(2,4-二氯苄基)锡配合物的合成、晶体结构、热稳定性及与DNA相互作用研究;冯泳兰等;《无机化学学报》;CNKI;20141231;第30卷(第12期);第2767-2774页 *
Self-Assembly of Organotin(IV) Moieties with the Schiff-Base Ligands Pyruvic Acid Isonicotinyl Hydrazone and Pyruvic Acid Salicylhydrazone: Synthesis, Characterization, and Crystal Structures of Monomeric or Polymeric Complexes;Handong Yin等;《Eur. J. Inorg. Chem.》;Wiley;20051118;第2005卷;第4572-4581页 *
含Sn2O2四元环苄基锡配合物的合成、晶体结构、热稳定性及与DNA相互作用研究;郑建华等;《衡阳师范学院学报》;20140630;第35卷(第3期);第171-176页 *
基于水杨酰腙配体的二丁基锡配合物的合成、晶体结构、热稳定性及与DNA相互作用;郑建华等;《应用化学》;20150531;第32卷(第5期);第562-569页 *

Also Published As

Publication number Publication date
CN105237564A (en) 2016-01-13

Similar Documents

Publication Publication Date Title
Dhahagani et al. Synthesis and spectral characterization of Schiff base complexes of Cu (II), Co (II), Zn (II) and VO (IV) containing 4-(4-aminophenyl) morpholine derivatives: Antimicrobial evaluation and anticancer studies
Raman et al. Synthesis, spectral characterization of Schiff base transition metal complexes: DNA cleavage and antimicrobial activity studies
Al-Shaalan Synthesis, characterization and biological activities of Cu (II), Co (II), Mn (II), Fe (II), and UO2 (VI) complexes with a new Schiff base hydrazone: O-Hydroxyacetophenone-7-chloro-4-quinoline hydrazone
Adams et al. The synthesis and antiparasitic activity of aryl-and ferrocenyl-derived thiosemicarbazone ruthenium (II)–arene complexes
Rehman et al. Synthesis, characterization, antimicrobial and antitumor screening of some diorganotin (IV) complexes of 2-[(9H-Purin-6-ylimino)]-phenol
Parish et al. Chemical and biological studies of dichloro (2-((dimethylamino) methyl) phenyl) gold (III)
Urquiola et al. Improving anti-trypanosomal activity of 3-aminoquinoxaline-2-carbonitrile N1, N4-dioxide derivatives by complexation with vanadium
Uozumi et al. Dinuclear nickel (II) complexes of an unsymmetric “end-off” compartmental ligand: conversion of urea into cyanate at a dinuclear nickel core
Abdel-Rahman et al. Synthesis, physicochemical studies, embryos toxicity and DNA interaction of some new Iron (II) Schiff base amino acid complexes
You et al. Synthesis, structures, and urease inhibitory activities of oxovanadium (V) complexes with Schiff bases
Root et al. Structural and spectroscopic characterization of dioxovanadium (V) complexes with asymmetric Schiff base ligands
Rosu et al. Complexes of 3dn metal ions with thiosemicarbazones: synthesis and antimicrobial activity
Kamalakannan et al. Synthesis and characterization of cobalt and nickel chelates of 5-dimethylaminomethyl-2-thiouracil and their evaluation as antimicrobial and anticancer agents
Ebrahimipour et al. Mono-and dioxido-vanadium (V) complexes of a tridentate ONO Schiff base ligand: Synthesis, spectral characterization, X-ray crystal structure, and anticancer activity
Rose et al. Ruthenium nitrosyls derived from polypyridine ligands with carboxamide or imine nitrogen donor (s): Isoelectronic complexes with different NO photolability
McLauchlan et al. Inhibition of acid, alkaline, and tyrosine (PTP1B) phosphatases by novel vanadium complexes
Abdel-Rahman et al. Design, characterization, teratogenicity testing, antibacterial, antifungal and DNA interaction of few high spin Fe (II) Schiff base amino acid complexes
Shafaatian et al. Synthesis, crystal structure, fluorescence and electrochemical studies of a new tridentate Schiff base ligand and its nickel (II) and palladium (II) complexes
Lobana et al. Synthesis, structures, spectroscopy and antimicrobial properties of complexes of copper (II) with salicylaldehyde N-substituted thiosemicarbazones and 2, 2′-bipyridine or 1, 10-phenanthroline
Sathisha et al. Synthesis, structure, electrochemistry, and spectral characterization of bis-isatin thiocarbohydrazone metal complexes and their antitumor activity against Ehrlich ascites carcinoma in Swiss albino mice
Mishra et al. Synthesis, structural investigation, DNA and protein binding study of some 3d-metal complexes with N′-(phenyl-pyridin-2-yl-methylene)-thiophene-2-carboxylic acid hydrazide
Gungor et al. Two tridentate Schiff base ligands and their mononuclear cobalt (III) complexes: Synthesis, characterization, antibacterial and antifungal activities
Fielden et al. Controlling aggregation of copper (II)-based coordination compounds: from mononuclear to dinuclear, tetranuclear, and polymeric copper complexes
CN103396436B (en) Monobutyltin substituted salicylic aldehydes contracting arylamine Schiff base complex and preparation method and application
Panchal et al. Bactericidal activity of different oxovanadium (IV) complexes with Schiff bases and application of chelation theory

Legal Events

Date Code Title Description
PB01 Publication
C06 Publication
SE01 Entry into force of request for substantive examination
C10 Entry into substantive examination
GR01 Patent grant
GR01 Patent grant