CN105237563B - A kind of 2 carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4 dichloro benzyl) tin complexs and its preparation method and application - Google Patents
A kind of 2 carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4 dichloro benzyl) tin complexs and its preparation method and application Download PDFInfo
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Abstract
The invention discloses a kind of 2 carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4 dichloro benzyl) tin complexs, for the complex of following structure formula (I), wherein R is 2,4 dichloro benzyls.The invention also discloses the preparation method of 2 carbonyl propionic acid para hydroxybenzene formyl hydrazone two (2,4 dichloro benzyl) the tin complex and the application in cancer therapy drug is prepared.
Description
Technical field
The present invention relates to a kind of (2,4- dichloro benzyls) tin complex of 2- carbonyl propionic acids para hydroxybenzene formyl hydrazone two and its system
Preparation Method, and 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyl) the tin complex is in cancer therapy drug is prepared
Application.
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 para hydroxybenzene formylhydrazine, Sodium Pyruvate and two (2,4- dichloro benzyl) stannous chloride react, synthesized under certain condition
Arrive to 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）Complex with certain inhibitory activity, provided for exploitation cancer therapy drug new
Approach.
The content of the invention
The first object of the present invention there is provided a kind of 2- carbonyl propionic acids para hydroxybenzene formyl hydrazone two (2,4- dichloro benzyls)
Tin complex.
The second object of the present invention is to provide above-mentioned 2- carbonyl propionic acids para hydroxybenzene formyl hydrazone two (2,4- dichloro benzyls) tin
Complex preparation method.
The third object of the present invention is to provide above-mentioned 2- carbonyl propionic acids para hydroxybenzene formyl hydrazone two (2,4- dichloro benzyls) tin
Application of the complex in cancer therapy drug is prepared.
A kind of 2- carbonyl propionic acids para hydroxybenzene formyl hydrazone two (2,4- dichloro benzyls) tin as the first aspect of the present invention
Complex, it is the complex of structure formula (I)
(I)
Wherein R is 2,4- dichloro benzyls.
(2,4- dichloro benzyls) the tin complex of 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two of the present invention is through elementary analysis, red
External spectrum, nuclear magnetic resoance spectrum and X-ray single crystal diffraction structural analysis, it is as a result as follows：
Elementary analysis (C25H22Cl4N2O5Sn)：Calculated value：C 43.46, H 3.21, N 4.05；Measured value：C 43.54, H
3.26, N 4.02.
FT-IR (KBr, ν/cm-1): 3633, 3257, 3194, 2939, 1606, 1473, 1392, 1317,
1286, 1213, 1168, 761, 638, 592, 538, 509, 468, 445。
1H NMR (400 MHz, DMSO-d 6) δ(ppm): 9.98 (s, 1H), 7.55 (d, J = 7.0 Hz,
2H), 6.98 (s, 1H), 6.74-6.82 (m, 4H), 7.62 (d, J = 7.6 Hz, 2H), 3.90 (s, 1H),
3.29(s, 3H), 2.82-2.89 (dt, J 1= 8.8 Hz, J 2= 11.3Hz, 4H), 1.80(s, 3H)。
13C NMR (100 MHz, 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 hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyl) tin complex of the present invention is crystal structure, its
Crystal is monoclinic system, space group 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) nm3, the Mgm of Dc=1.665-3, m (MoK α)=
1.353 mm-1, F (000)=1376.
2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) tin complex of the present invention is structurally characterized in that：
Tin atom is hexa-coordinate distorted octahedron configuration in molecule.
A kind of 2- carbonyl propionic acids para hydroxybenzene formyl hydrazone two (2,4- dichloro benzyls) tin as the second aspect of the present invention
The preparation method of complex, two (2,4- dichloro benzyl) stannous chloride are added in the reaction vessel for having nitrogen to protect, to hydroxyl
Benzoyl hydrazine, Sodium Pyruvate and solvent absolute methanols, 5 ~ 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, obtains rufous transparent crystal, as 2- carbonyl propionic acids para hydroxybenzene formyl
Hydrazone two (2,4- dichloro benzyls) tin complex.
In a preferred embodiment of the invention, described two (2,4- dichloro benzyl) stannous chloride, para hydroxybenzene formyl
Hydrazine, Sodium Pyruvate three material amount ratio be 1:(1~1.05):(1.05~1.15).
In a preferred embodiment of the invention, the solvent absolute methanol dosage is every mM two (2,4- dichloros
Benzyl) stannous chloride adds 15 ~ 35 milliliters.
(2,4- dichloro benzyls) the tin complex preparation method of 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two of the present invention is one
Pot method, will whole raw materials add in reactor directly react together, without the separation of intermediate, 2- carbonyls are directly prepared
Propionic acid para hydroxybenzene formyl hydrazone two (2,4- dichloro benzyls) tin complex.And the customary preparation methods of this area are first to be prepared
Part, then complex is prepared in part and the starting compound reaction containing metal, 2- carbonyl propionic acids of the invention are to hydroxyl
(2,4- dichloro benzyl) the tin complex of benzoyl hydrazone two preparation method compares this area customary preparation methods, has and saves centre
The last handling process of step, the advantages that saving substantial amounts of human and material resources, financial resources.
A kind of 2- carbonyl propionic acids para hydroxybenzene formyl hydrazone two (2,4- dichloro benzyls) tin as the third aspect of the present invention
Application of the complex in cancer therapy drug is prepared.
Applicant has carried out body to above-mentioned 2- carbonyl propionic acids para hydroxybenzene formyl hydrazone two (2,4- dichloro benzyls) tin complex
Outer antitumor activity determines research, it is thus identified that 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyl) tin complex has
There is certain anticancer bioactive, that is to say, that the purposes of above-mentioned complex is the application in cancer therapy drug is prepared, specifically
Say to be exactly the application in anti-human colon cancer, human liver cancer, human breast carcinoma, human cervical carcinoma, human lung cancer medicine is prepared.
2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) tin complex of the present invention is thin to human colon carcinoma
Born of the same parents, human liver cancer cell, human breast cancer cell, human cervical carcinoma cell, human lung carcinoma cell etc. show good active anticancer, this
(2,4- dichloro benzyls) the tin complex active anticancer of 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two of invention is high, cost is low, prepares
The features such as method is simple, the cancer therapy drug to develop new provide new way.
Brief description of the drawings
Fig. 1 is the IR spectrograms of 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) tin complex.
Fig. 2 is 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) tin complex1H NMR spectras.
Fig. 3 is 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) tin complex13C NMR spectras.
Fig. 4 is the crystal structure figure of 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) tin complex.
Fig. 5 is the TG-DTG curves of 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) 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：
The preparation of 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) tin complex：
0.510g (1.0mmol) two (2,4- dichloro benzyls) dichloro is added in the 100mL three-necked flasks for having nitrogen to protect
Change tin, 0.152g (1.0mmol) para hydroxybenzenes formylhydrazine, 0.121g (1.1mmol) Sodium Pyruvates and 25mL solvents without water beetle
Alcohol, 8 h are reacted under conditions of being 45 ~ 65 DEG C in temperature, are cooled down, filtering, solvent volatilization knot is controlled under conditions of 20 ~ 35 DEG C
Crystalline substance, obtain rufous transparent crystal, as 2- carbonyl propionic acids para hydroxybenzene formyl hydrazone two (2,4- dichloro benzyl) tin complex.Production
Rate：66.8%.Fusing point：149~150℃(dec).
Elementary analysis (C25H22Cl4N2O5Sn)：Calculated value：C 43.46, H 3.21, N 4.05；Measured value：C 43.54, H
3.26, N 4.02.
FT-IR (KBr, ν/cm-1): 3633, 3257, 3194, 2939, 1606, 1473, 1392, 1317,
1286, 1213, 1168, 761, 638, 592, 538, 509, 468, 445。
1H NMR (400 MHz, DMSO-d 6) δ(ppm): 9.98 (s, 1H), 7.55 (d, J = 7.0 Hz,
2H), 6.98 (s, 1H), 6.74-6.82 (m, 4H), 7.62 (d, J = 7.6 Hz, 2H), 3.90 (s, 1H),
3.29(s, 3H), 2.82-2.89 (dt, J 1= 8.8 Hz, J 2= 11.3Hz, 4H), 1.80(s, 3H)。
13C NMR (100 MHz, 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：Monoclinic system, space group 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) nm3, Dc=1.665
Mg·m-3, m (MoK α)=1.353 mm-1, F (000)=1376.
Embodiment 2：
The preparation of 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) tin complex：
0.510g (1.0mmol) two (2,4- dichloro benzyls) dichloro is added in the 100mL three-necked flasks for having nitrogen to protect
Change tin, 0.152g (1.0mmol) para hydroxybenzenes formylhydrazine, 0.116g (1.05mmol) Sodium Pyruvates and 35mL solvents without water beetle
Alcohol, 5 h are reacted under conditions of being 45 ~ 65 DEG C in temperature, are cooled down, filtering, solvent volatilization knot is controlled under conditions of 20 ~ 35 DEG C
Crystalline substance, obtain rufous transparent crystal, as 2- carbonyl propionic acids para hydroxybenzene formyl hydrazone two (2,4- dichloro benzyl) tin complex.Production
Rate：70.4%.Fusing point：149~150℃(dec).
Elementary analysis (C25H22Cl4N2O5Sn)：Calculated value：C 43.46, H 3.21, N 4.05；Measured value：C 43.54, H
3.26, N 4.02.
FT-IR (KBr, ν/cm-1): 3633, 3257, 3194, 2939, 1606, 1473, 1392, 1317,
1286, 1213, 1168, 761, 638, 592, 538, 509, 468, 445。
1H NMR (400 MHz, DMSO-d 6) δ(ppm): 9.98 (s, 1H), 7.55 (d, J = 7.0 Hz,
2H), 6.98 (s, 1H), 6.74-6.82 (m, 4H), 7.62 (d, J = 7.6 Hz, 2H), 3.90 (s, 1H),
3.29(s, 3H), 2.82-2.89 (dt, J 1= 8.8 Hz, J 2= 11.3Hz, 4H), 1.80(s, 3H)。
13C NMR (100 MHz, 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：Monoclinic system, space group 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) nm3, Dc=1.665
Mg·m-3, m (MoK α)=1.353 mm-1, F (000)=1376.
Embodiment 3：
The preparation of 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) tin complex：
0.510g (1.0mmol) two (2,4- dichloro benzyls) dichloro is added in the 100mL three-necked flasks for having nitrogen to protect
It is anhydrous to change tin, 0.160g (1.05mmol) para hydroxybenzenes formylhydrazine, 0.127g (1.15mmol) Sodium Pyruvates and 30mL solvents
Methanol, 15 h are reacted under conditions of being 45 ~ 65 DEG C in temperature, are cooled down, filtering, solvent volatilization is controlled under conditions of 20 ~ 35 DEG C
Crystallization, obtains rufous transparent crystal, as 2- carbonyl propionic acids para hydroxybenzene formyl hydrazone two (2,4- dichloro benzyl) tin complex.Production
Rate：69.9%.Fusing point：149~150℃(dec).
Elementary analysis (C25H22Cl4N2O5Sn)：Calculated value：C 43.46, H 3.21, N 4.05；Measured value：C 43.54, H
3.26, N 4.02.
FT-IR (KBr, ν/cm-1): 3633, 3257, 3194, 2939, 1606, 1473, 1392, 1317,
1286, 1213, 1168, 761, 638, 592, 538, 509, 468, 445。
1H NMR (400 MHz, DMSO-d 6) δ(ppm): 9.98 (s, 1H), 7.55 (d, J = 7.0 Hz,
2H), 6.98 (s, 1H), 6.74-6.82 (m, 4H), 7.62 (d, J = 7.6 Hz, 2H), 3.90 (s, 1H),
3.29(s, 3H), 2.82-2.89 (dt, J 1= 8.8 Hz, J 2= 11.3Hz, 4H), 1.80(s, 3H)。
13C NMR (100 MHz, 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：Monoclinic system, space group 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) nm3, Dc=1.665
Mg·m-3, m (MoK α)=1.353 mm-1, F (000)=1376.
Embodiment 4：
The preparation of 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) tin complex：
2.550g (5.0mmol) two (2,4- dichloro benzyls) dichloro is added in the 250mL three-necked flasks for having nitrogen to protect
Change tin, 0.775g (5.1mmol) para hydroxybenzenes formylhydrazine, 0.594g (5.4mmol) Sodium Pyruvates and 100mL solvents without water beetle
Alcohol, 20 h are reacted under conditions of being 45 ~ 65 DEG C in temperature, are cooled down, filtering, solvent volatilization knot is controlled under conditions of 20 ~ 35 DEG C
Crystalline substance, obtain rufous transparent crystal, as 2- carbonyl propionic acids para hydroxybenzene formyl hydrazone two (2,4- dichloro benzyl) tin complex.Production
Rate：68.4%.Fusing point：149~150℃(dec).
Elementary analysis (C25H22Cl4N2O5Sn)：Calculated value：C 43.46, H 3.21, N 4.05；Measured value：C 43.54, H
3.26, N 4.02.
FT-IR (KBr, ν/cm-1): 3633, 3257, 3194, 2939, 1606, 1473, 1392, 1317,
1286, 1213, 1168, 761, 638, 592, 538, 509, 468, 445。
1H NMR (400 MHz, DMSO-d 6) δ(ppm): 9.98 (s, 1H), 7.55 (d, J = 7.0 Hz,
2H), 6.98 (s, 1H), 6.74-6.82 (m, 4H), 7.62 (d, J = 7.6 Hz, 2H), 3.90 (s, 1H),
3.29(s, 3H), 2.82-2.89 (dt, J 1= 8.8 Hz, J 2= 11.3Hz, 4H), 1.80(s, 3H)。
13C NMR (100 MHz, 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：Monoclinic system, space group 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) nm3, Dc=1.665
Mg·m-3, m (MoK α)=1.353 mm-1, F (000)=1376.
Embodiment 5：
The preparation of 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) tin complex：
2.550g (5.0mmol) two (2,4- dichloro benzyls) dichloro is added in the 250mL three-necked flasks for having nitrogen to protect
Change tin, 0.790g (5.2mmol) para hydroxybenzenes formylhydrazine, 0.616g (5.6mmol) Sodium Pyruvates and 150mL solvents without water beetle
Alcohol, 22 h are reacted under conditions of being 45 ~ 65 DEG C in temperature, are cooled down, filtering, solvent volatilization knot is controlled under conditions of 20 ~ 35 DEG C
Crystalline substance, obtain rufous transparent crystal, as 2- carbonyl propionic acids para hydroxybenzene formyl hydrazone two (2,4- dichloro benzyl) tin complex.Production
Rate：67.6%.Fusing point：149~150℃(dec).
Elementary analysis (C25H22Cl4N2O5Sn)：Calculated value：C 43.46, H 3.21, N 4.05；Measured value：C 43.54, H
3.26, N 4.02.
FT-IR (KBr, ν/cm-1): 3633, 3257, 3194, 2939, 1606, 1473, 1392, 1317,
1286, 1213, 1168, 761, 638, 592, 538, 509, 468, 445。
1H NMR (400 MHz, DMSO-d 6) δ(ppm): 9.98 (s, 1H), 7.55 (d, J = 7.0 Hz,
2H), 6.98 (s, 1H), 6.74-6.82 (m, 4H), 7.62 (d, J = 7.6 Hz, 2H), 3.90 (s, 1H),
3.29(s, 3H), 2.82-2.89 (dt, J 1= 8.8 Hz, J 2= 11.3Hz, 4H), 1.80(s, 3H)。
13C NMR (100 MHz, 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：Monoclinic system, space group 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) nm3, Dc=1.665
Mg·m-3, m (MoK α)=1.353 mm-1, F (000)=1376.
Embodiment 6：
The preparation of 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) tin complex：
5.100g (10.0mmol) two (2,4- dichloro benzyls) two is added in the 250mL three-necked flasks for having nitrogen to protect
Stannic chloride, 1.550g (10.2mmol) para hydroxybenzenes formylhydrazine, 1.166g (10.6mmol) Sodium Pyruvates and 150mL solvents without
Water methanol, 24 h are reacted under conditions of being 45 ~ 65 DEG C in temperature, cools down, filtering, controls solvent to wave under conditions of 20 ~ 35 DEG C
Hair crystallization, obtains rufous transparent crystal, as 2- carbonyl propionic acids para hydroxybenzene formyl hydrazone two (2,4- dichloro benzyl) tin complex.
Yield：66.2%.Fusing point：149~150℃(dec).
Elementary analysis (C25H22Cl4N2O5Sn)：Calculated value：C 43.46, H 3.21, N 4.05；Measured value：C 43.54, H
3.26, N 4.02.
FT-IR (KBr, ν/cm-1): 3633, 3257, 3194, 2939, 1606, 1473, 1392, 1317,
1286, 1213, 1168, 761, 638, 592, 538, 509, 468, 445。
1H NMR (400 MHz, DMSO-d 6) δ(ppm): 9.98 (s, 1H), 7.55 (d, J = 7.0 Hz,
2H), 6.98 (s, 1H), 6.74-6.82 (m, 4H), 7.62 (d, J = 7.6 Hz, 2H), 3.90 (s, 1H),
3.29(s, 3H), 2.82-2.89 (dt, J 1= 8.8 Hz, J 2= 11.3Hz, 4H), 1.80(s, 3H)。
13C NMR (100 MHz, 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：Monoclinic system, space group 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) nm3, Dc=1.665
Mg·m-3, m (MoK α)=1.353 mm-1, F (000)=1376.
Test example：
2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyl) tin complex of the present invention, its external anticancer are lived
Property measure 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.
The 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) of the preparation of embodiment 1 is determined using mtt assay
Tin complex is to human colon cancer cell（Colo205）, human liver cancer cell（HepG2）, human breast cancer cell（MCF7）, human cervical cancer 1
Cancer cell（Hela）And human lung carcinoma cell（NCI-H460）Inhibitory activity.
Cell line and cultivating system：Colo205, HepG2, MCF7, Hela and NCI-H460 cell line are derived from American. tissue
Incubator（ATCC）.With the RPMI 1640 containing 10% hyclone（GIBICO companies）Culture medium, 5%（Volume fraction）CO2、
In vitro culture is carried out in 37 DEG C of saturated humidity incubators.
Test process：Decoction will be tested（0.1ng/mL~10ug/mL）Concentration gradient according to concentration is added separately to each
Kong Zhong, each concentration set 6 parallel holes.Experiment is divided into drug study group（It is separately added into the test medicine of various concentrations）, control group
（Only add nutrient solution and cell, be not added with testing medicine）And blank group（Only plus medicine is cultivated, be not added with cell and test medicine）.After dosing
Orifice plate is placed in 37 DEG C, 5%CO272h is cultivated in incubator.The activity of control drug determines according to the method for test sample.Cultivating
In orifice plate after 72h, add MTT 40uL per hole（4mg/mL is made into D-Hanks buffer solutions）.After 37 DEG C are placed 4h, remove
Supernatant liquor.Add 150uL DMSO per hole, vibrate 5min, make Formazan crystallization dissolvings.Finally, existed using automatic ELIASA
The optical density in each hole is detected at 570nm wavelength.
Data processing：Data processing uses the programs of Graph Pad Prism version 5.0, complex IC50Pass through journey
The nonlinear regression model (NLRM) with S-shaped dose response is fitted to obtain in sequence.
With MTT analytic approach to human colon cancer cell（Colo205）, human liver cancer cell（HepG2）, human breast cancer cell
（MCF7）, human cervical carcinoma cell（Hela）And human lung carcinoma cell（NCI-H460）Cell line is analyzed, and determines its IC50Value,
As a result as shown in table 1, conclusion is：From data in table, with the 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- of the present invention
Dichloro benzyl) tin complex is used as cancer therapy drug, to human colon cancer cell（Colo205）, human liver cancer cell（HepG2）, human milk
Adenocarcinoma cell（MCF7）, human cervical carcinoma cell（Hela）And human lung carcinoma cell（NCI-H460）With certain drug effect, can make
For the candidate compound of cancer therapy drug.
Table 1 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) tin complex cancer therapy drug external activity
Test data.
2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) tin complex prepared by remaining embodiment is with MTT
Method is 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- carbonyl propionic acids para hydroxybenzene formyl hydrazone two (2,4- dichloro benzyl) tin complex, it is following structure formula (I)
Complex：
(I)
Wherein R is 2,4- dichloro benzyls；Described complex (I) is crystal structure, and its crystallographic data is as follows：Monoclinic system,
Space group 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) nm3, the Mgm of Dc=1.665-3, m (MoK α)=1.353 mm-1, F
(000) = 1376；Tin atom is hexa-coordinate distorted octahedron configuration in molecule；The infrared spectrum number of described complex (I)
According to：FT-IR (KBr, ν/cm-1): 3633, 3257, 3194, 2939, 1606, 1473, 1392, 1317, 1286,
1213, 1168, 761, 638, 592, 538, 509, 468, 445；Nuclear-magnetism modal data：1H NMR (400 MHz,
DMSO-d 6) δ(ppm): 9.98 (s, 1H), 7.55 (d, J = 7.0 Hz, 2H), 6.98 (s, 1H), 6.74-
6.82 (m, 4H), 7.62 (d, J = 7.6 Hz, 2H), 3.90 (s, 1H), 3.29(s, 3H), 2.82-2.89
(dt, J 1= 8.8 Hz, J 2= 11.3Hz, 4H), 1.80(s, 3H)；13C NMR (100 MHz, 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；Described complex (I) has certain thermostabilization scope, can be steady below 149 DEG C
It is fixed to exist.
2. the preparation side of 2- carbonyl propionic acid para hydroxybenzenes formyl hydrazone two (2,4- dichloro benzyls) tin complex described in claim 1
Method, it is characterized in that adding two (2,4- dichloro benzyl) stannous chloride, para hydroxybenzene formyl in the reaction vessel for thering is nitrogen to protect
Hydrazine, Sodium Pyruvate and solvent absolute methanol, 5 ~ 24 h are reacted under conditions of being 45 ~ 65 DEG C in temperature, are cooled down, filtering, 20 ~ 35
Solvent volatilization crystallization is controlled under conditions of DEG C, obtains rufous transparent crystal, as 2- carbonyl propionic acids para hydroxybenzene formyl hydrazone two (2,
4- dichloro benzyls) tin complex.
3. preparation method as claimed in claim 2, it is characterised in that described two (2,4- dichloro benzyl) stannous chloride, to hydroxyl
Base benzoyl hydrazine, Sodium Pyruvate three material amount ratio be 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 every mM two
(2,4- dichloro benzyls) 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. (2,4- dichloro benzyls) the tin complex of 2- carbonyl propionic acids para hydroxybenzene formyl hydrazone two described in claim 1 is preparing anticancer
Application in medicine.
7. the application described in claim 6, wherein the cancer cell is that human colon cancer cell, human liver cancer cell, human breast carcinoma are thin
Born of the same parents, human cervical carcinoma cell, human lung carcinoma cell.
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| 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 |
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