CN105198921B - A kind of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex and its preparation method and application - Google Patents
A kind of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex and its preparation method and application Download PDFInfo
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Abstract
The invention discloses a kind of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complexs, are the complex of following structure formula (I), wherein Ph is phenyl, and n-Bu is normal-butyl.The invention also discloses the preparation method of the 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex and preparing the application in anticancer drug.
Description
Technical field
The present invention relates to a kind of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex and preparation method thereof, with
And the 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex is preparing the application in anticancer drug.
Background technique
Organotin is a kind of metallo-organic compound containing Sn-C key.Researcher just notices before very early
The Anticancer Activity in vitro of organo-tin compound.1972, Brown had found Ph for the first time3SnOOCCH3To the growth tool of mouse cancer cell
There is inhibiting effect.1980, Crowe etc. chemists' studies have shown that many organo-tin compounds have anti tumor activity in vitro.
1989, American National anticancer research institute (National Cancer Institute) to more than 2,000 kinds of organo-tin compounds into
Antitumor activity screening is gone, the results showed that some organo-tin compounds have inhibiting effect to P388 lymphocytic leukemia.
2002, Gielen et al. did comprehensive summing up in the activity to organotin carboxylate's ester compounds, thought many organic after research
Tin compound has preferable Anticancer Activity in vitro really.
Studies have shown that the organic group connected on organic tin atom and the ligand for participating in being coordinated decide organo-tin compound
Bioactivity, select it is some itself with the active organic ligand of good biological in organotin tin atoms be coordinated causes
The great interest of people.Acylhydrazone is one kind Schiff alkali cpd made of being modified as hydrazide kind compound, it
Be condensed by aldehydes or ketones and hydrazides, with good bioactivity, stronger coordination ability and multiplicity coordination mode, and
And medicine, pesticide, material and in terms of have a wide range of applications.In recent years, domestic and international many researchers couple
It compares in terms of bioactivity and in depth studies, and research finds that acylhydrazone has anticancer, sterilization, anti-inflammatory etc.
Various active.Therefore, by acylhydrazone class Schiff aar ligand in conjunction with organotin, it is intended to obtain the stronger new chemical combination of bioactivity
Object becomes the interested research direction of people.
Chinese patent CN 102718794A disclose a kind of double acylhydrazone class Schiff alkali stannous phenide complexs and its
Prepare Antilung gland cancer, colon cancer, leukaemia cell drug in application.
Chinese patent CN 101851251A disclose a kind of acylhydrazone class Schiff aar ligand dibutyl tin complex and
Its application in the drug of preparation treatment liver cancer, adenocarcinoma of lung, breast cancer, prostate cancer, colon cancer or early young grain leukaemia.
Document (Journal of Organometallic Chemistry, 2014,75:83-91) report, organotin
Acylhydrazone class Schiff alkali complex is to human colon cancer cell (HCT-116), human lung adenocarcinoma cell (A549), human umblilical vein endothelial
Cell (HUVEC) 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 ligand are respectively to human lung adenocarcinoma
The inhibiting effect of the cancer cells such as cell (A549), human colon cancer cell (HCT-8), people in loop (hl-60).
Document (Bioorganic & Medicinal Chemistry Letters, 2015,25:4461- 4463)
Report, a variety of acylhydrazone class Schiff aar ligands are living to the anticancer of human liver cancer cell (HuH-7) and human lung adenocarcinoma cell (A549)
Property.
It is the experiment proved that the substance with anticancer activity, the present invention based on acylhydrazone class Schiff alkali organotin complex
Selection salicylyl hydrazine, benzoyl formic acid react under certain condition with Dibutyltin oxide, and synthesis has obtained thin to human colon carcinoma
Born of the same parents (Colo205), human liver cancer cell (HepG2), breast cancer cell (MCF7), cervical cancer cell (Hela) and human lung carcinoma cell
(NCI-H460) with the complex of certain inhibitory activity, new approach is provided for exploitation anticancer drug.
Summary of the invention
There is provided a kind of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complexs for the first object of the present invention.
The second object of the present invention is to provide above-mentioned 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex preparation
Method.
The third object of the present invention is to provide above-mentioned 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex and is making
Application in standby anticancer drug.
A kind of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex as the first aspect of the present invention is
The complex of structure formula (I)
(I)
Wherein Ph is phenyl, and n-Bu is normal-butyl.
2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex of the invention is through elemental analysis, infrared spectroscopy, core
Magnetic resonance spectrum and X-ray single crystal diffraction structural analysis, as a result as follows:
Elemental analysis (C48H64N4O10Sn2): calculated value: C 52.68, H 5.89, N 5.12；Measured value: C 52.64, H
5.86, N 5.09.
FT-IR (KBr, ν/cm-1): 3570, 3057, 2956, 2924, 1685, 1662, 1595, 1510,
1487, 1444, 1325, 1257, 1165, 1097, 723, 690, 596, 447。
1H NMR (400 MHz, CDCl3) δ(ppm): 11.61 (s, 1H), 7.95 (m, 3H), 7.59 (s,
3H), 7.42 (m, 1H), 6.94 (m, 2H), 3.49 (s, 3H), 1.70-1.78 (m, 8H), 1.38-1.43
(m, 4H), 0.98 (s, 1H), 0.90-0.94 (m, 6H)。
13C NMR (100 MHz, CDCl3) δ(ppm): 176.12, 167.28, 160.53, 148.48,
134.69, 131.22, 130.14, 129.80, 129.26, 128.30, 118.92, 117.34, 115.45,
50.35, 28.98, 26.98, 26.08, 13.39。
2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex of the invention is crystal structure, and crystal is single
Oblique system, space group P2 (1)/n, a=1.11632 (5) nm, b=1.61078 (7) nm, c=1.42139 (6) nm, α
=γ=90 °, β=95.7610 (10) °, Z=4, V=2.54296 (19) nm3, the Mgm of Dc=1.429-3, m (MoK α)=
1.039 mm-1, F (000)=1120.
2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex of the invention is structurally characterized in that: tin in molecule
Atom is seven coordination distortion pentagonal bipyramid configurations.
A kind of system of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex as a second aspect of the invention
It is anhydrous that Dibutyltin oxide, salicylyl hydrazine, benzoyl formic acid and solvent is added in Preparation Method in the reaction vessel for having nitrogen protection
Methanol reacts 5 ~ 24 h under conditions of temperature is 45 ~ 65 DEG C, and cooling, filtering controls solvent under conditions of 20 ~ 35 DEG C and waves
Hair crystallization, obtains yellow transparent crystal, as 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex.
In a preferred embodiment of the invention, the Dibutyltin oxide, salicylyl hydrazine, benzoyl formic acid three
The mass ratio of the material is 1:(1 ~ 1.05): (1.05 ~ 1.15).
In a preferred embodiment of the invention, the solvent anhydrous methanol dosage is every mM of Dibutyltin oxide
Add 15 ~ 35 milliliters.
2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex preparation method of the invention is one kettle way, i.e., will
Whole raw materials are added in reactor together directly to react, and without the separation of intermediate, 2- carbonyl -2- phenyl second is directly prepared
Sour salicyloyl hydrazone dibutyl tin complex.And the customary preparation methods of this field be first be prepared ligand, then by ligand with contain
Complex, 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin of the invention is prepared in the raw material compound reaction of metal
Complex preparation method compares this field customary preparation methods, has the last handling process for saving intermediate steps, saves big
The advantages that human and material resources of amount, financial resources.
A kind of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex as the third aspect of the present invention is being made
Application in standby anticancer drug.
It is living that applicant has carried out extracorporeal anti-tumor to above-mentioned 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex
Property determine research, it is thus identified that 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex has certain Anti-cancer biologic living
Property, that is to say, that the purposes of above-mentioned complex is to prepare the application in anticancer drug, is specifically exactly to prepare anti-human knot
Intestinal cancer, human liver cancer, human breast carcinoma, human cervical carcinoma, the application in human lung cancer drug.
2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex of the invention is to human colon cancer cell, human liver cancer
Cell, human breast cancer cell, human cervical carcinoma cell, human lung carcinoma cell etc. show good anticancer activity, 2- of the invention
The features such as carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex anticancer activity is high, at low cost, preparation method is simple be
It develops new anticancer drug and provides new way.
Detailed description of the invention
Fig. 1 is the IR spectrogram of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex.
Fig. 2 is 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex1H NMR spectra.
Fig. 3 is 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex13C NMR spectra.
Fig. 4 is the crystal structure figure of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex.
Fig. 5 is the TG-DTG curve of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex.
Specific embodiment
By following embodiment, present invention be described in more detail, but should be noted that the scope of the present invention is not implemented by these
Any restrictions of example.
Embodiment 1:
The preparation of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex:
0.249g (1.0mmol) Dibutyltin oxide, 0.152g are added in the 100mL three-necked flask for having nitrogen protection
(1.0mmol) salicylyl hydrazine, 0.165g (1.1mmol) benzoyl formic acid and 25mL solvent anhydrous methanol are 45 ~ 65 in temperature
8 h are reacted under conditions of DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains yellow transparent crystal,
As 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex.Yield: 83.4%.Fusing point: 80 ~ 82 DEG C (dec).
Elemental analysis (C48H64N4O10Sn2): calculated value: C 52.68, H 5.89, N 5.12；Measured value: C 52.64, H
5.86, N 5.09.
FT-IR (KBr, ν/cm-1): 3570, 3057, 2956, 2924, 1685, 1662, 1595, 1510,
1487, 1444, 1325, 1257, 1165, 1097, 723, 690, 596, 447。
1H NMR (400 MHz, CDCl3) δ(ppm): 11.61 (s, 1H), 7.95 (m, 3H), 7.59 (s,
3H), 7.42 (m, 1H), 6.94 (m, 2H), 3.49 (s, 3H), 1.70-1.78 (m, 8H), 1.38-1.43
(m, 4H), 0.98 (s, 1H), 0.90-0.94 (m, 6H)。
13C NMR (100 MHz, CDCl3) δ(ppm): 176.12, 167.28, 160.53, 148.48,
134.69, 131.22, 130.14, 129.80, 129.26, 128.30, 118.92, 117.34, 115.45,
50.35, 28.98, 26.98, 26.08, 13.39。
Crystallographic data: monoclinic system, space group P2 (1)/n, a=1.11632 (5) nm, b=1.61078 (7)
Nm, c=1.42139 (6) nm, α=γ=90 °, β=95.7610 (10) °, Z=4, V=2.54296 (19) nm3, Dc=
1.429 Mg·m-3, m (MoK α)=1.039 mm-1, F (000)=1120.
Embodiment 2:
The preparation of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex:
0.249g (1.0mmol) Dibutyltin oxide, 0.152g are added in the 100mL three-necked flask for having nitrogen protection
(1.0mmol) salicylyl hydrazine, 0.158g (1.05mmol) benzoyl formic acid and 35mL solvent anhydrous methanol are 45 ~ 65 in temperature
5 h are reacted under conditions of DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains yellow transparent crystal,
As 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex.Yield: 85.6%.Fusing point: 80 ~ 82 DEG C (dec).
Elemental analysis (C48H64N4O10Sn2): calculated value: C 52.68, H 5.89, N 5.12；Measured value: C 52.64, H
5.86, N 5.09.
FT-IR (KBr, ν/cm-1): 3570, 3057, 2956, 2924, 1685, 1662, 1595, 1510,
1487, 1444, 1325, 1257, 1165, 1097, 723, 690, 596, 447。
1H NMR (400 MHz, CDCl3) δ(ppm): 11.61 (s, 1H), 7.95 (m, 3H), 7.59 (s,
3H), 7.42 (m, 1H), 6.94 (m, 2H), 3.49 (s, 3H), 1.70-1.78 (m, 8H), 1.38-1.43
(m, 4H), 0.98 (s, 1H), 0.90-0.94 (m, 6H)。
13C NMR (100 MHz, CDCl3) δ(ppm): 176.12, 167.28, 160.53, 148.48,
134.69, 131.22, 130.14, 129.80, 129.26, 128.30, 118.92, 117.34, 115.45,
50.35, 28.98, 26.98, 26.08, 13.39。
Crystallographic data: monoclinic system, space group P2 (1)/n, a=1.11632 (5) nm, b=1.61078 (7)
Nm, c=1.42139 (6) nm, α=γ=90 °, β=95.7610 (10) °, Z=4, V=2.54296 (19) nm3, Dc=
1.429 Mg·m-3, m (MoK α)=1.039 mm-1, F (000)=1120.
Embodiment 3:
The preparation of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex:
0.249g (1.0mmol) Dibutyltin oxide, 0.160g are added in the 100mL three-necked flask for having nitrogen protection
(1.05mmol) salicylyl hydrazine, 0.173g (1.15mmol) benzoyl formic acid and 30mL solvent anhydrous methanol, temperature be 45 ~
15 h are reacted under conditions of 65 DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains yellow transparent crystalline substance
Body, as 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex.Yield: 85.8%.Fusing point: 80 ~ 82 DEG C (dec).
Elemental analysis (C48H64N4O10Sn2): calculated value: C 52.68, H 5.89, N 5.12；Measured value: C 52.64, H
5.86, N 5.09.
FT-IR (KBr, ν/cm-1): 3570, 3057, 2956, 2924, 1685, 1662, 1595, 1510,
1487, 1444, 1325, 1257, 1165, 1097, 723, 690, 596, 447。
1H NMR (400 MHz, CDCl3) δ(ppm): 11.61 (s, 1H), 7.95 (m, 3H), 7.59 (s,
3H), 7.42 (m, 1H), 6.94 (m, 2H), 3.49 (s, 3H), 1.70-1.78 (m, 8H), 1.38-1.43
(m, 4H), 0.98 (s, 1H), 0.90-0.94 (m, 6H)。
13C NMR (100 MHz, CDCl3) δ(ppm): 176.12, 167.28, 160.53, 148.48,
134.69, 131.22, 130.14, 129.80, 129.26, 128.30, 118.92, 117.34, 115.45,
50.35, 28.98, 26.98, 26.08, 13.39。
Crystallographic data: monoclinic system, space group P2 (1)/n, a=1.11632 (5) nm, b=1.61078 (7)
Nm, c=1.42139 (6) nm, α=γ=90 °, β=95.7610 (10) °, Z=4, V=2.54296 (19) nm3, Dc=
1.429 Mg·m-3, m (MoK α)=1.039 mm-1, F (000)=1120.
Embodiment 4:
The preparation of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex:
1.245g (5.0mmol) Dibutyltin oxide, 0.775g are added in the 250mL three-necked flask for having nitrogen protection
(5.1mmol) salicylyl hydrazine, 0.810g (5.4mmol) benzoyl formic acid and 100mL solvent anhydrous methanol are 45 ~ 65 in temperature
20 h are reacted under conditions of DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains yellow transparent crystalline substance
Body, as 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex.Yield: 82.9%.Fusing point: 80 ~ 82 DEG C (dec).
Elemental analysis (C48H64N4O10Sn2): calculated value: C 52.68, H 5.89, N 5.12；Measured value: C 52.64, H
5.86, N 5.09.
FT-IR (KBr, ν/cm-1): 3570, 3057, 2956, 2924, 1685, 1662, 1595, 1510,
1487, 1444, 1325, 1257, 1165, 1097, 723, 690, 596, 447。
1H NMR (400 MHz, CDCl3) δ(ppm): 11.61 (s, 1H), 7.95 (m, 3H), 7.59 (s,
3H), 7.42 (m, 1H), 6.94 (m, 2H), 3.49 (s, 3H), 1.70-1.78 (m, 8H), 1.38-1.43
(m, 4H), 0.98 (s, 1H), 0.90-0.94 (m, 6H)。
13C NMR (100 MHz, CDCl3) δ(ppm): 176.12, 167.28, 160.53, 148.48,
134.69, 131.22, 130.14, 129.80, 129.26, 128.30, 118.92, 117.34, 115.45,
50.35, 28.98, 26.98, 26.08, 13.39。
Crystallographic data: monoclinic system, space group P2 (1)/n, a=1.11632 (5) nm, b=1.61078 (7)
Nm, c=1.42139 (6) nm, α=γ=90 °, β=95.7610 (10) °, Z=4, V=2.54296 (19) nm3, Dc=
1.429 Mg·m-3, m (MoK α)=1.039 mm-1, F (000)=1120.
Embodiment 5:
The preparation of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex:
1.245g (5.0mmol) Dibutyltin oxide, 0.790g are added in the 250mL three-necked flask for having nitrogen protection
(5.2mmol) salicylyl hydrazine, 0.840g (5.6mmol) benzoyl formic acid and 150mL solvent anhydrous methanol are 45 ~ 65 in temperature
22 h are reacted under conditions of DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains yellow transparent crystalline substance
Body, as 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex.Yield: 82.5%.Fusing point: 80 ~ 82 DEG C (dec).
Elemental analysis (C48H64N4O10Sn2): calculated value: C 52.68, H 5.89, N 5.12；Measured value: C 52.64, H
5.86, N 5.09.
FT-IR (KBr, ν/cm-1): 3570, 3057, 2956, 2924, 1685, 1662, 1595, 1510,
1487, 1444, 1325, 1257, 1165, 1097, 723, 690, 596, 447。
1H NMR (400 MHz, CDCl3) δ(ppm): 11.61 (s, 1H), 7.95 (m, 3H), 7.59 (s,
3H), 7.42 (m, 1H), 6.94 (m, 2H), 3.49 (s, 3H), 1.70-1.78 (m, 8H), 1.38-1.43
(m, 4H), 0.98 (s, 1H), 0.90-0.94 (m, 6H)。
13C NMR (100 MHz, CDCl3) δ(ppm): 176.12, 167.28, 160.53, 148.48,
134.69, 131.22, 130.14, 129.80, 129.26, 128.30, 118.92, 117.34, 115.45,
50.35, 28.98, 26.98, 26.08, 13.39。
Crystallographic data: monoclinic system, space group P2 (1)/n, a=1.11632 (5) nm, b=1.61078 (7)
Nm, c=1.42139 (6) nm, α=γ=90 °, β=95.7610 (10) °, Z=4, V=2.54296 (19) nm3, Dc=
1.429 Mg·m-3, m (MoK α)=1.039 mm-1, F (000)=1120.
Embodiment 6:
The preparation of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex:
2.490g (10.0mmol) Dibutyltin oxide, 1.550g are added in the 250mL three-necked flask for having nitrogen protection
(10.2mmol) salicylyl hydrazine, 1.590g (10.6mmol) benzoyl formic acid and 150mL solvent anhydrous methanol, temperature be 45 ~
24 h are reacted under conditions of 65 DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains yellow transparent crystalline substance
Body, as 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex.Yield: 81.7%.Fusing point: 80 ~ 82 DEG C (dec).
Elemental analysis (C48H64N4O10Sn2): calculated value: C 52.68, H 5.89, N 5.12；Measured value: C 52.64, H
5.86, N 5.09.
FT-IR (KBr, ν/cm-1): 3570, 3057, 2956, 2924, 1685, 1662, 1595, 1510,
1487, 1444, 1325, 1257, 1165, 1097, 723, 690, 596, 447。
1H NMR (400 MHz, CDCl3) δ(ppm): 11.61 (s, 1H), 7.95 (m, 3H), 7.59 (s,
3H), 7.42 (m, 1H), 6.94 (m, 2H), 3.49 (s, 3H), 1.70-1.78 (m, 8H), 1.38-1.43
(m, 4H), 0.98 (s, 1H), 0.90-0.94 (m, 6H)。
13C NMR (100 MHz, CDCl3) δ(ppm): 176.12, 167.28, 160.53, 148.48,
134.69, 131.22, 130.14, 129.80, 129.26, 128.30, 118.92, 117.34, 115.45,
50.35, 28.98, 26.98, 26.08, 13.39。
Crystallographic data: monoclinic system, space group P2 (1)/n, a=1.11632 (5) nm, b=1.61078 (7)
Nm, c=1.42139 (6) nm, α=γ=90 °, β=95.7610 (10) °, Z=4, V=2.54296 (19) nm3, Dc=
1.429 Mg·m-3, m (MoK α)=1.039 mm-1, F (000)=1120.
Test example:
2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex of the invention, Anticancer Activity in vitro measurement are
It is realized by MTT experiment method.
MTT analytic approach:
3- (4,5-Dimethylthiazol-2-yl) -2,5-diphenyltetrazolium is restored with metabolism
Based on bromide.Succinate dehydrogenase in living cells mitochondria can make exogenous MTT be reduced to the bluish violet of water-insoluble
Crystallization first a ceremonial jade-ladle, used in libation (Formazan) is simultaneously deposited in cell, and dead cell is without this function.Dimethyl sulfoxide (DMSO) can dissolve cell
In first a ceremonial jade-ladle, used in libation, with microplate reader measurement characteristic wavelength optical density, can reflect living cells quantity indirectly.
2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin the complex pair of the preparation of embodiment 1 is measured using mtt assay
Human colon cancer cell (Colo205), human liver cancer cell (HepG2), human breast cancer cell (MCF7), human cervical carcinoma cell
(Hela) and the inhibitory activity of human lung carcinoma cell (NCI-H460).
Cell strain and cultivating system: Colo205, HepG2, MCF7, Hela and NCI-H460 cell strain are derived from American tissue
Incubator (ATCC).With the RPMI 1640(GIBICO company for containing 10% fetal calf serum) culture medium, in 5%(volume fraction) CO2、
In vitro culture is carried out in 37 DEG C of saturated humidity incubators.
Test process: will test medical fluid (0.1ng/mL ~ 10ug/mL) be added separately to according to the concentration gradient of concentration it is each
Kong Zhong, each concentration set 6 parallel holes.Experiment is divided into drug study group (the test medicine for being separately added into various concentration), control group
(only adding culture solution and cell, test medicine is not added) and blank group (only adding culture medicine, cell and test medicine is not added).After dosing
Orifice plate is placed in 37 DEG C, 5%CO272h is cultivated in incubator.The activity of control drug is measured according to the method for test sample.It is cultivating
In orifice plate after 72h, every hole adds MTT 40uL(to be made into 4mg/mL with D-Hanks buffer).After 37 DEG C of placement 4h, remove
Supernatant liquor.Every hole adds 150uL DMSO, vibrates 5min, makes Formazan crystallization dissolution.Finally, being existed using automatic microplate reader
The optical density in each hole is detected at 570nm wavelength.
Data processing: data processing uses 5.0 program of Graph Pad Prism version, complex IC50Pass through journey
Nonlinear regression model (NLRM) in sequence with S-shaped dose response is fitted to obtain.
With MTT analytic approach to human colon cancer cell (Colo205), human liver cancer cell (HepG2), human breast cancer cell
(MCF7), human cervical carcinoma cell (Hela) and human lung carcinoma cell (NCI-H460) cell strain are analyzed, and measure its IC50Value,
The results are shown in Table 1, conclusion are as follows: from the data in the table, with 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl of the invention
Tin complex is used as anticancer drug, to human colon cancer cell (Colo205), human liver cancer cell (HepG2), human breast cancer cell
(MCF7), human cervical carcinoma cell (Hela) and human lung carcinoma cell (NCI-H460) have certain drug effect, can be used as anticarcinogen
The candidate compound of object.
1 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex anticancer drug external activity test data of table.
2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin the complex of remaining embodiment preparation ties people with mtt assay
Colon-cancer cell (Colo205), human liver cancer cell (HepG2), human breast cancer cell (MCF7), human cervical carcinoma cell (Hela) and
The same test example of anticancer activity test method of human lung carcinoma cell (NCI-H460), test result and table 1 are essentially identical.
Claims (8)
1. a kind of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex is the complex of following structure formula (I):
(I)
Wherein Ph is phenyl, and n-Bu is normal-butyl；The complex (I) is crystal structure, and crystallographic data is as follows: monocline
Crystallographic system, space group P2 (1)/n, a=1.11632 (5) nm, b=1.61078 (7) nm, c=1.42139 (6) nm, α=
γ=90 °, β=95.7610 (10) °, Z=4, V=2.54296 (19) nm3, the Mgm of Dc=1.429-3, m (MoK α)=1.039
mm-1, F (000)=1120；Tin atom is seven coordination distortion pentagonal bipyramid configurations in molecule.
2. a kind of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex as described in claim 1, infrared spectroscopy
Data: FT-IR (KBr, ν/cm-1): 3570, 3057, 2956, 2924, 1685, 1662, 1595, 1510,
1487, 1444, 1325, 1257, 1165, 1097, 723, 690, 596, 447；Its nuclear-magnetism modal data:1H NMR
(400 MHz, CDCl3) δ(ppm): 11.61 (s, 1H), 7.95 (m, 3H), 7.59 (s, 3H), 7.42 (m,
1H), 6.94 (m, 2H), 3.49 (s, 3H), 1.70-1.78 (m, 8H), 1.38-1.43 (m, 4H), 0.98
(s, 1H), 0.90-0.94 (m, 6H)；13C NMR (100 MHz, CDCl3) δ(ppm): 176.12, 167.28,
160.53, 148.48, 134.69, 131.22, 130.14, 129.80, 129.26, 128.30, 118.92,
117.34, 115.45, 50.35, 28.98, 26.98, 26.08, 13.39。
3. 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex described in claim 1, which is characterized in that have one
Fixed thermostabilization range, can be stabilized at 80 DEG C or less.
4. the preparation method of 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex described in claim 1, feature
It is that Dibutyltin oxide, salicylyl hydrazine, benzoyl formic acid and solvent anhydrous methanol are added in the reaction vessel for having nitrogen protection,
5 ~ 24 h are reacted under conditions of temperature is 45 ~ 65 DEG C, cooling, filtering controls solvent volatilization knot under conditions of 20 ~ 35 DEG C
Crystalline substance obtains yellow transparent crystal, as 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex.
5. the method prepared as claimed in claim 4, which is characterized in that the Dibutyltin oxide, salicylyl hydrazine, benzoyl
The mass ratio of the material of formic acid three is 1:(1 ~ 1.05): (1.05 ~ 1.15).
6. the method prepared as claimed in claim 4, which is characterized in that the solvent anhydrous methanol dosage is every mM two
Butyl tin oxide adds 15 ~ 35 milliliters.
7. the method prepared as claimed in claim 4, which is characterized in that prepared using one kettle way.
8. 2- carbonyl -2- phenylacetic acid salicyloyl hydrazone dibutyl tin complex is in preparing anticancer drug described in claim 1
Using, which is characterized in that the cancer cell of the application is human colon cancer cell, human liver cancer cell, human breast cancer cell, people uterus
Neck cancer cell, human lung carcinoma cell.
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