CN107033181A - A kind of chlorination Dibenzyltin dimethylglyoxime complex and preparation method and application - Google Patents
A kind of chlorination Dibenzyltin dimethylglyoxime complex and preparation method and application Download PDFInfo
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- CN107033181A CN107033181A CN201710198108.XA CN201710198108A CN107033181A CN 107033181 A CN107033181 A CN 107033181A CN 201710198108 A CN201710198108 A CN 201710198108A CN 107033181 A CN107033181 A CN 107033181A
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- chlorination
- dibenzyltin
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- dimethylglyoxime
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- 238000005660 chlorination reaction Methods 0.000 title claims abstract description 42
- GFQSZQQSYPHTBR-UHFFFAOYSA-N CC(C(=NO)C)=NO.C(C1=CC=CC=C1)[Sn]CC1=CC=CC=C1 Chemical compound CC(C(=NO)C)=NO.C(C1=CC=CC=C1)[Sn]CC1=CC=CC=C1 GFQSZQQSYPHTBR-UHFFFAOYSA-N 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 238000010668 complexation reaction Methods 0.000 title description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
- 239000003814 drug Substances 0.000 claims description 19
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 17
- 239000013078 crystal Substances 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 14
- 229910052708 sodium Inorganic materials 0.000 claims description 14
- 239000011734 sodium Substances 0.000 claims description 14
- 206010006187 Breast cancer Diseases 0.000 claims description 11
- 229940079593 drug Drugs 0.000 claims description 11
- 208000026310 Breast neoplasm Diseases 0.000 claims description 10
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 10
- 229910052718 tin Inorganic materials 0.000 claims description 10
- 238000002425 crystallisation Methods 0.000 claims description 9
- 230000008025 crystallization Effects 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- 229910020813 Sn-C Inorganic materials 0.000 claims description 8
- 229910018732 Sn—C Inorganic materials 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 229910020923 Sn-O Inorganic materials 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 7
- 238000002447 crystallographic data Methods 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- 201000005202 lung cancer Diseases 0.000 claims description 7
- 208000020816 lung neoplasm Diseases 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- JGUQDUKBUKFFRO-CIIODKQPSA-N dimethylglyoxime Chemical compound O/N=C(/C)\C(\C)=N\O JGUQDUKBUKFFRO-CIIODKQPSA-N 0.000 claims description 5
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 claims description 3
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 2
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- SVSRQMUJHHQAAX-UHFFFAOYSA-N dibenzyltin Chemical compound C=1C=CC=CC=1C[Sn]CC1=CC=CC=C1 SVSRQMUJHHQAAX-UHFFFAOYSA-N 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 230000000118 anti-neoplastic effect Effects 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 27
- 201000005296 lung carcinoma Diseases 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 238000011275 oncology therapy Methods 0.000 description 8
- 230000001093 anti-cancer Effects 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 201000008275 breast carcinoma Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 2
- -1 Tricyclohexyltin carboxylate Chemical class 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 125000000972 4,5-dimethylthiazol-2-yl group Chemical group [H]C([H])([H])C1=C(N=C(*)S1)C([H])([H])[H] 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- FPALBTZUZRQNCQ-UHFFFAOYSA-N CC(C(=NO)C)=NO.[Sn] Chemical compound CC(C(=NO)C)=NO.[Sn] FPALBTZUZRQNCQ-UHFFFAOYSA-N 0.000 description 1
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 201000008274 breast adenocarcinoma Diseases 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 201000011216 nasopharynx carcinoma Diseases 0.000 description 1
- ODOPKAJVFRHHGM-UHFFFAOYSA-N phenyltin Chemical compound [Sn]C1=CC=CC=C1 ODOPKAJVFRHHGM-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- RNVJQUPAEIQUTC-UHFFFAOYSA-N tricyclohexyltin Chemical compound C1CCCCC1[Sn](C1CCCCC1)C1CCCCC1 RNVJQUPAEIQUTC-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/22—Tin compounds
- C07F7/2284—Compounds with one or more Sn-N linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/22—Tin compounds
- C07F7/2296—Purification, stabilisation, isolation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A kind of chlorination Dibenzyltin dimethylglyoxime complex disclosed by the invention and preparation method and application, is that R represents benzyl in the complex of following structure formula (I), formula.The invention also discloses the preparation method of chlorination Dibenzyltin dimethylglyoxime complex and the application in antineoplastic is prepared.
Description
Technical field
The present invention relates to a kind of chlorination Dibenzyltin dimethylglyoxime complex, and preparation method thereof, and the chlorination dibenzyl
Application of the base tin dimethylglyoxime complex in antineoplastic is prepared.
Background technology
Organotin is the metallo-organic compound that a class contains Sn-C keys, with higher bioactivity, is sterilizing, is killing
The fields such as worm, cancer therapy drug preparation have a wide range of applications.Existing research shows that the alkyl R in organotin is to determine
The principal element of compound anti-cancering activity height, e.g., the active anticancer of cyclohexyl, normal-butyl and phenyl tin compound are stronger, second
Base takes second place, and methyl is then almost without active anticancer.The structure of part is to the active anticancer of complex and the wide spectrum of killing cancer cell
Property also plays an important role.
Chinese patent CN 103396437B disclose Tricyclohexyltin carboxylate and are preparing treatment cervical carcinoma, breast cancer, liver
Applied in the medicine of cancer, colon cancer and lung cancer.
Chinese patent CN 103087325B disclose being controlled in preparation for the carboxylate polymer of Tricyclohexyltin containing ferrocenyl
Applied in the medicine for treating liver cancer, nasopharyngeal carcinoma, breast cancer, colon cancer and lung cancer.
It is that the experiment proved that the material with preferable bioactivity based on organotin complex, present invention selection dibenzyl two
Stannic chloride, with part dimethylglyoxime, is reacted under certain condition, and synthesis has been obtained to NCI-H460 (human lung carcinoma cell), A549
(human lung carcinoma cell), the stronger compound of MCF7 (people's breast adenocarcinoma cell) inhibitory activity provides for exploitation cancer therapy drug
New way.
The content of the invention
In view of the above-mentioned problems of the prior art, the first object of the present invention there is provided a kind of chlorination Dibenzyltin fourth
Diketone oxime complex.
The second object of the present invention is to provide the preparation method of above-mentioned chlorination Dibenzyltin dimethylglyoxime complex.
The 3rd mesh of the present invention is to provide above-mentioned chlorination Dibenzyltin dimethylglyoxime complex in cancer therapy drug is prepared
Using.
As a kind of chlorination Dibenzyltin dimethylglyoxime complex of first aspect present invention, it is following structure formula (I)
Complex, R represents benzyl in formula：
The chlorination Dibenzyltin dimethylglyoxime complex of the present invention is analyzed through elementary analysis, infrared spectrum analysis, as a result such as
Under：
Elementary analysis (C64H70Cl2N4O6Sn4)：Theoretical value：C, 50.01；H, 4.59；N, 3.65.Measured value：C, 50.06；
H, 4.65；N, 3.58.
IR(KBr,v/cm-1):3294,3057,3024,2920v(C-H),561v(Sn-C),482v(Sn-N),451v
(Sn-O)。
The chlorination Dibenzyltin dimethylglyoxime complex of the present invention is crystal structure, its crystallographic data：It is oblique that crystal belongs to three
Crystallographic system, space groupA=1.05304 (10) nm, b=1.18349 (11) nm, c=1.43092 (13) nm, α=70.1260
(10) °, β=73.6400 (10) °, γ=87.9800 (10) °, Z=1, V=1.6056 (3) nm3, Dc=1.59Mgm-3, μ
(MoKa)=1.672mm-1, F (000)=764,2.64 ° of 26.00 ° of ＜ θ ＜, crystalline size：0.23 × 0.22 × 0.21mm, R=
0.0453, wR=0.1066.
The chlorination Dibenzyltin dimethylglyoxime complex of the present invention is structurally characterized in that：Exist in molecule with tin and oxygen atom
The Sn of composition2O2There is two kinds of coordination modes in planar four-element ring, and with tin, the five-membered ring that oxygen and nitrogen-atoms are constituted, complex
A kind of tin atom, tin atom is hexa-coordinate, and another tin atom is pentacoordinate.
As a kind of preparation method of chlorination Dibenzyltin dimethylglyoxime complex of second aspect of the present invention, hold in reaction
Ethanol, metallic sodium, dimethylglyoxime, TriphenylphosphineoxComplex are sequentially added in device in order, in the condition that temperature is 80~90 DEG C
8~12h of lower reaction；Cooling, filtering controls solvent volatilization crystallization under conditions of 20~35 DEG C, obtains colourless transparent crystal, be
Chlorination Dibenzyltin dimethylglyoxime complex.
In a preferred embodiment of the invention, the sodium, dimethylglyoxime, TriphenylphosphineoxComplex, triethylamine
Mol ratio be 2:1:(2~2.1):1.
In a preferred embodiment of the invention, the etoh solvent consumption is that every mM of TriphenylphosphineoxComplex adds
20~35 milliliters.
As a kind of chlorination Dibenzyltin dimethylglyoxime complex of third aspect present invention in cancer therapy drug is prepared
Using.
Applicant has carried out anti tumor activity in vitro to above-mentioned complex and has confirmed research, confirms that the complex has necessarily
Anti-tumor biological, that is to say, that the purposes of above-mentioned complex is the application in antineoplastic is prepared, specifically
It is the application in anti-human lung-cancer medicament, human breast carcinoma medicine is prepared.
The chlorination Dibenzyltin dimethylglyoxime complex of the present invention shows good to human lung cancer medicine, human breast carcinoma etc.
Active anticancer, can prepare anti-lung cancer, anti-breast cancer medicines using it as raw material.With the platinum-containing anticancer drug phase generally used at present
Than chlorination Dibenzyltin dimethylglyoxime complex of the invention has the spies such as active anticancer is high, cost is low, preparation method is simple
Point, new way is provided for exploitation cancer therapy drug.
Brief description of the drawings
Fig. 1 is the crystal molecular structure figure of chlorination Dibenzyltin dimethylglyoxime complex.
Fig. 2 is the IR spectrograms of chlorination Dibenzyltin dimethylglyoxime 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 limitation of example.
Embodiment 1：
The preparation of chlorination Dibenzyltin dimethylglyoxime complex：
Ethanol 40mL, sodium 0.046 (2mmol) are first added in 100ml round-bottomed flasks, fourth two is added after sodium has reacted
Ketoxime 0.1163g (1mmol), heating reflux reaction is after 10 minutes, then adds TriphenylphosphineoxComplex 0.7438g (2mmol), three second
Amine 0.1013 (1mmol), 8h is reacted under conditions of temperature is 80~90 DEG C；Cooling, filtering is controlled under conditions of 20~35 DEG C
Solvent volatilization crystallization processed, obtains colourless transparent crystal, as chlorination Dibenzyltin dimethylglyoxime complex.Yield：72%, fusing point：
184-185℃。
Elementary analysis (C64H70Cl2N4O6Sn4)：Theoretical value：C, 50.01；H, 4.59；N, 3.65.Measured value：C, 50.06；
H, 4.65；N, 3.58.
IR(KBr,v/cm-1):3294,3057,3024,2920v(C-H),561v(Sn-C),482v(Sn-N),451v
(Sn-O)。
Its crystallographic data：Crystal belongs to anorthic system, space groupA=1.05304 (10) nm, b=1.18349 (11)
Nm, c=1.43092 (13) nm, α=70.1260 (10) °, β=73.6400 (10) °, γ=87.9800 (10) °, Z=1, V=
1.6056(3)nm3, Dc=1.59Mgm-3, μ (MoKa)=1.672mm-1, F (000)=764,2.64 ° of 26.00 ° of ＜ θ ＜ are brilliant
Body size：0.23 × 0.22 × 0.21mm, R=0.0453, wR=0.1066.
Embodiment 2：
The preparation of chlorination Dibenzyltin dimethylglyoxime complex：
Ethanol 70mL, sodium 0.044 (2mmol) are first added in 100ml round-bottomed flasks, fourth two is added after sodium has reacted
Ketoxime 0.1165g (1mmol), heating reflux reaction is after 10 minutes, then adds TriphenylphosphineoxComplex 0.7434g (2mmol), three second
Amine 0.1018 (1mmol), 8h is reacted under conditions of temperature is 80~90 DEG C；Cooling, filtering is controlled under conditions of 20~35 DEG C
Solvent volatilization crystallization processed, obtains colourless transparent crystal, as chlorination Dibenzyltin dimethylglyoxime complex.Yield：71%, fusing point：
184-185℃。
Elementary analysis (C64H70Cl2N4O6Sn4)：Theoretical value：C, 50.01；H, 4.59；N, 3.65.Measured value：C, 50.06；
H, 4.65；N, 3.58.
IR(KBr,v/cm-1):3294,3057,3024,2920v(C-H),561v(Sn-C),482v(Sn-N),451v
(Sn-O)。
Its crystallographic data：Crystal belongs to anorthic system, space groupA=1.05304 (10) nm, b=1.18349 (11)
Nm, c=1.43092 (13) nm, α=70.1260 (10) °, β=73.6400 (10) °, γ=87.9800 (10) °, Z=1, V=
1.6056(3)nm3, Dc=1.59Mgm-3, μ (MoKa)=1.672mm-1, F (000)=764,2.64 ° of 26.00 ° of ＜ θ ＜ are brilliant
Body size：0.23 × 0.22 × 0.21mm, R=0.0453, wR=0.1066.
Embodiment 3：
The preparation of chlorination Dibenzyltin dimethylglyoxime complex：
Ethanol 70mL, sodium 0.046 (2mmol) are first added in 100ml round-bottomed flasks, fourth two is added after sodium has reacted
Ketoxime 0.1163g (1mmol), heating reflux reaction is after 10 minutes, then adds TriphenylphosphineoxComplex 0.7802g (2.1mmol), three
Ethamine 0.1012 (1mmol), 8h is reacted under conditions of temperature is 80~90 DEG C；Cooling, filtering, under conditions of 20~35 DEG C
Solvent volatilization crystallization is controlled, colourless transparent crystal, as chlorination Dibenzyltin dimethylglyoxime complex is obtained.Yield：71%, melt
Point：184-185℃.
Elementary analysis (C64H70Cl2N4O6Sn4)：Theoretical value：C, 50.01；H, 4.59；N, 3.65.Measured value：C, 50.06；
H, 4.65；N, 3.58.
IR(KBr,v/cm-1):3294,3057,3024,2920v(C-H),561v(Sn-C),482v(Sn-N),451v
(Sn-O)。
Its crystallographic data：Crystal belongs to anorthic system, space groupA=1.05304 (10) nm, b=1.18349 (11)
Nm, c=1.43092 (13) nm, α=70.1260 (10) °, β=73.6400 (10) °, γ=87.9800 (10) °, Z=1, V=
1.6056(3)nm3, Dc=1.59Mgm-3, μ (MoKa)=1.672mm-1, F (000)=764,2.64 ° of 26.00 ° of ＜ θ ＜ are brilliant
Body size：0.23 × 0.22 × 0.21mm, R=0.0453, wR=0.1066.
Embodiment 4：
The preparation of chlorination Dibenzyltin dimethylglyoxime complex：
Ethanol 40mL, sodium 0.047 (2mmol) are first added in 100ml round-bottomed flasks, fourth two is added after sodium has reacted
Ketoxime 0.1165g (1mmol), heating reflux reaction is after 10 minutes, then adds TriphenylphosphineoxComplex 0.7436g (2mmol), three second
Amine 0.1017 (1mmol), 10h is reacted under conditions of temperature is 80~90 DEG C；Cooling, filtering, under conditions of 20~35 DEG C
Solvent volatilization crystallization is controlled, colourless transparent crystal, as chlorination Dibenzyltin dimethylglyoxime complex is obtained.Yield：75%, melt
Point：184-185℃.
Elementary analysis (C64H70Cl2N4O6Sn4)：Theoretical value：C, 50.01；H, 4.59；N, 3.65.Measured value：C, 50.06；
H, 4.65；N, 3.58.
IR(KBr,v/cm-1):3294,3057,3024,2920v(C-H),561v(Sn-C),482v(Sn-N),451v
(Sn-O)。
Its crystallographic data：Crystal belongs to anorthic system, space groupA=1.05304 (10) nm, b=1.18349 (11)
Nm, c=1.43092 (13) nm, α=70.1260 (10) °, β=73.6400 (10) °, γ=87.9800 (10) °, Z=1, V=
1.6056(3)nm3, Dc=1.59Mgm-3, μ (MoKa)=1.672mm-1, F (000)=764,2.64 ° of 26.00 ° of ＜ θ ＜ are brilliant
Body size：0.23 × 0.22 × 0.21mm, R=0.0453, wR=0.1066.
Embodiment 5：
The preparation of chlorination Dibenzyltin dimethylglyoxime complex：
Ethanol 40mL, sodium 0.045 (2mmol) are first added in 100ml round-bottomed flasks, fourth two is added after sodium has reacted
Ketoxime 0.1160g (1mmol), heating reflux reaction is after 10 minutes, then adds TriphenylphosphineoxComplex 0.7433g (2mmol), three second
Amine 0.1013 (1mmol), 12h is reacted under conditions of temperature is 80~90 DEG C；Cooling, filtering, under conditions of 20~35 DEG C
Solvent volatilization crystallization is controlled, colourless transparent crystal, as chlorination Dibenzyltin dimethylglyoxime complex is obtained.Yield：75%, melt
Point：184-185℃.
Elementary analysis (C64H70Cl2N4O6Sn4)：Theoretical value：C, 50.01；H, 4.59；N, 3.65.Measured value：C, 50.06；
H, 4.65；N, 3.58.
IR(KBr,v/cm-1):3294,3057,3024,2920v(C-H),561v(Sn-C),482v(Sn-N),451v
(Sn-O)。
Its crystallographic data：Crystal belongs to anorthic system, space groupA=1.05304 (10) nm, b=1.18349 (11)
Nm, c=1.43092 (13) nm, α=70.1260 (10) °, β=73.6400 (10) °, γ=87.9800 (10) °, Z=1, V=
1.6056(3)nm3, Dc=1.59Mgm-3, μ (MoKa)=1.672mm-1, F (000)=764,2.64 ° of 26.00 ° of ＜ θ ＜ are brilliant
Body size：0.23 × 0.22 × 0.21mm, R=0.0453, wR=0.1066.
Test example：
The chlorination Dibenzyltin dimethylglyoxime complex of the present invention, it is by MTT experiment side that its Anticancer Activity in vitro, which is determined,
What method was realized.
MTT analyses method：
To be metabolized reduction 3- (4,5-Dimethylthiazol-2-yl) -2,5-diArenyltetrazolium
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) (DMSO) can dissolve cell
In first a ceremonial jade-ladle, used in libation, with ELIASA determine characteristic wavelength optical density, living cells quantity can be reflected indirectly.
The chlorination Dibenzyltin dimethylglyoxime complex of the preparation of embodiment 1 is determined using mtt assay to human lung carcinoma cell
(NCI-H460), human lung carcinoma cell (A549), the inhibitory activity of human breast cancer cell (MCF7).
Cell line and cultivating system：NCI-H460, A549 and MCF7 cell line are derived from American. tissue incubator (ATCC).With
RPMI1640 (GIBICO companies) culture medium containing 10% hyclone, in 5% (volume fraction) CO2, 37 DEG C of saturated humidity trainings
Support and in vitro culture is carried out in case.
Test process：Test decoction (0.0032uM-10uM) is added separately to each hole according to the concentration gradient of concentration
In, each concentration sets 3 parallel holes.Experiment is divided into drug test group (the test medicine for being separately added into various concentrations), control group (only
Plus nutrient solution and cell, it is not added with testing medicine) and blank group (only adding nutrient solution, be not added with cell and test medicine).By the hole after dosing
Plate is placed in 37 DEG C, 5%CO272h is cultivated in incubator.The activity of control drug is determined according to the method for test sample.In culture
In orifice plate after 72h, add MTT40uL (being made into 4mg/mL with D-Hanks buffer solutions) per hole.After 37 DEG C are placed 4h, remove
Supernatant.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 GraAr Pad Prism version5.0 programs, compound IC50Pass through program
In there is S-shaped dose response nonlinear regression model (NLRM) be fitted and obtain.
With MTT analytic approach to human lung carcinoma cell (NCI-H460) cell line, human lung carcinoma cell (A549) cell line, people's mammary gland
Cancer cell (MCF7) cell line is analyzed, and determines its IC50Value, as a result as shown in table 1, conclusion is：The data in table, this
The chlorination Dibenzyltin dimethylglyoxime complex of invention is higher to human lung cancer, human breast carcinoma activity as cancer therapy drug, can conduct
The candidate compound of cancer therapy drug.
The chlorination Dibenzyltin dimethylglyoxime complex cancer therapy drug external activity test data of table 1.
| Human lung carcinoma cell | Human lung carcinoma cell | Human breast cancer cell | |
| Cell line | NCI-H460 | A549 | MCF7 |
| IC50μM | 3.32 | 1.24 | 0.30 |
Chlorination Dibenzyltin dimethylglyoxime complex prepared by remaining embodiment is with mtt assay to human lung carcinoma cell (NCI-
H460), the same test example of active anticancer method of testing of human lung carcinoma cell (A549) and human breast cancer cell (MCF7), test result
It is essentially identical with table 1.
Claims (8)
1. a kind of chlorination Dibenzyltin dimethylglyoxime complex, it is characterised in that be the complex of following structure formula (I)：
R represents benzyl in formula.
2. contain a kind of chlorination Dibenzyltin dimethylglyoxime complex, its ir data as claimed in claim 1：FT-
IR(KBr,v/cm-1):3294,3057,3024,2920v(C-H),561v(Sn-C),482v(Sn-N),451v(Sn-O)。
3. chlorination Dibenzyltin dimethylglyoxime complex as claimed in claim 1, wherein, described chlorination Dibenzyltin fourth two
Ketoxime complex is crystal structure, and its crystallographic data is as follows：Anorthic system, space group, a=1.05304 (10) nm, b=
1.18349 (11) nm, c=1.43092 (13) nm, α=70.1260 (10) °, β=73.6400 (10) °, γ=87.9800
(10) °, Z=1, V=1.6056 (3) nm3, there is the Sn constituted with tin and oxygen atom in molecule2O2Planar four-element ring, and with tin,
There is the tin atom of two kinds of coordination modes in the five-membered ring that oxygen and nitrogen-atoms are constituted, complex, a kind of tin atom is hexa-coordinate, separately
A kind of tin atom is pentacoordinate.
4. the preparation method of the chlorination Dibenzyltin dimethylglyoxime complex described in any one of claims 1 to 3 claim, its
It is characterised by, ethanol, metallic sodium, dimethylglyoxime, TriphenylphosphineoxComplex is sequentially added in order in reaction vessel, in temperature
To react 8~12h under conditions of 80~90 DEG C；Cooling, filtering controls solvent volatilization crystallization under conditions of 20~35 DEG C, obtained
Colourless transparent crystal, as chlorination Dibenzyltin dimethylglyoxime complex.
5. preparation method as claimed in claim 4, it is characterised in that the sodium, dimethylglyoxime, TriphenylphosphineoxComplex, three
The mol ratio of ethamine is 2:1:(2~2.1):1.
6. preparation method as claimed in claim 4, it is characterised in that the etoh solvent consumption is every mM of dibenzyl two
Stannic chloride adds 20~and 35 milliliters.
7. the chlorination Dibenzyltin dimethylglyoxime complex described in any one of claims 1 to 3 claim is preparing treatment cancer
Application in disease drug.
8. the application described in claim 7, wherein the cancer is lung cancer or breast cancer.
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