CN107141315A - A kind of di-n-butyl tin O-methoxy nicotinate complex and preparation method and application - Google Patents
A kind of di-n-butyl tin O-methoxy nicotinate complex and preparation method and application Download PDFInfo
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- CN107141315A CN107141315A CN201710198109.4A CN201710198109A CN107141315A CN 107141315 A CN107141315 A CN 107141315A CN 201710198109 A CN201710198109 A CN 201710198109A CN 107141315 A CN107141315 A CN 107141315A
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- tin
- methoxy
- complex
- butyl tin
- butyl
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- -1 di-n-butyl tin O-methoxy nicotinate Chemical compound 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 238000010668 complexation reaction Methods 0.000 title description 3
- 239000013078 crystal Substances 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 18
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 15
- JGFBRKRYDCGYKD-UHFFFAOYSA-N dibutyl(oxo)tin Chemical compound CCCC[Sn](=O)CCCC JGFBRKRYDCGYKD-UHFFFAOYSA-N 0.000 claims description 12
- YCKFVYHOESURQZ-UHFFFAOYSA-N methyl pyridine-3-carboperoxoate Chemical compound COOC(=O)C1=CC=CN=C1 YCKFVYHOESURQZ-UHFFFAOYSA-N 0.000 claims description 11
- 229910020923 Sn-O Inorganic materials 0.000 claims description 10
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 10
- 206010006187 Breast cancer Diseases 0.000 claims description 9
- 208000026310 Breast neoplasm Diseases 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 8
- 238000002447 crystallographic data Methods 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- 229910052718 tin Inorganic materials 0.000 claims description 8
- 201000005202 lung cancer Diseases 0.000 claims description 6
- 208000020816 lung neoplasm Diseases 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- WCRDXYSYPCEIAK-UHFFFAOYSA-N dibutylstannane Chemical compound CCCC[SnH2]CCCC WCRDXYSYPCEIAK-UHFFFAOYSA-N 0.000 claims description 3
- 235000001968 nicotinic acid Nutrition 0.000 claims description 3
- 239000011664 nicotinic acid Substances 0.000 claims description 3
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 2
- 229910020813 Sn-C Inorganic materials 0.000 claims description 2
- 229910018732 Sn—C Inorganic materials 0.000 claims description 2
- 229910009053 Sn—O—Sn Chemical group 0.000 claims description 2
- 241000826860 Trapezium Species 0.000 claims description 2
- ZHUXMBYIONRQQX-UHFFFAOYSA-N hydroxidodioxidocarbon(.) Chemical group [O]C(O)=O ZHUXMBYIONRQQX-UHFFFAOYSA-N 0.000 claims description 2
- QHGNHLZPVBIIPX-UHFFFAOYSA-N tin(ii) oxide Chemical compound [Sn]=O QHGNHLZPVBIIPX-UHFFFAOYSA-N 0.000 claims description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 239000003560 cancer drug Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 230000000118 anti-neoplastic effect Effects 0.000 abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- 210000004027 cell Anatomy 0.000 description 26
- 239000003814 drug Substances 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 11
- 229940079593 drug Drugs 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 238000002425 crystallisation Methods 0.000 description 9
- 230000008025 crystallization Effects 0.000 description 9
- 201000005296 lung carcinoma Diseases 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 230000001093 anti-cancer Effects 0.000 description 8
- 238000011275 oncology therapy Methods 0.000 description 8
- 238000000902 119Sn nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- 230000000694 effects Effects 0.000 description 4
- 201000008275 breast carcinoma Diseases 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- AYOHIQLKSOJJQH-UHFFFAOYSA-N dibutyltin Chemical compound CCCC[Sn]CCCC AYOHIQLKSOJJQH-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 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
- 238000001228 spectrum Methods 0.000 description 2
- 201000011549 stomach cancer Diseases 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
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 239000002262 Schiff base 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
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 201000008274 breast adenocarcinoma Diseases 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000007942 carboxylates Chemical class 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
- 150000002148 esters Chemical class 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 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
- 201000011216 nasopharynx carcinoma Diseases 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 201000008006 pharynx cancer 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
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 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
- 238000001942 tin-119 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000012549 training Methods 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
- C07F7/2224—Compounds having one or more tin-oxygen linkages
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
A kind of di-n-butyl tin O-methoxy nicotinate complex disclosed by the invention and preparation method and application, is that R represents normal-butyl in the complex of following structure formula (I), formula.The invention also discloses di-n-butyl tin O-methoxy nicotinate complex preparation method and the application in antineoplastic is prepared.
Description
Technical field
The present invention relates to a kind of di-n-butyl tin O-methoxy nicotinate complex, and preparation method thereof, and this is two just
Application of the butyl tin O-methoxy nicotinate 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, it is demonstrated experimentally that the bioactivity of organotin carboxylate complex is often than corresponding organotin
Compound is high.
Chinese patent CN101402650B disclose a kind of dibutyl tin and quinolinecarboxylic acid complex prepare treatment stomach cancer,
Applied in the medicine of nasopharyngeal carcinoma, human liver cancer or leukaemia.
Chinese patent CN101434616B discloses a kind of dibutyl tin Schiff base complex and is preparing treatment stomach cancer, nose
Applied in the medicine of pharynx cancer, human liver cancer or leukaemia.
Ester type compound based on aromatic carboxylic acids and dibutyl tin formation is to the experiment proved that the material with active anticancer,
Present invention selection Dibutyltin oxide, with part O-methoxy nicotinic acid, reacts, synthesis has been obtained to NCI- under certain condition
The stronger compound of H460 (human lung carcinoma cell), A549 (human lung carcinoma cell), MCF7 (people's breast adenocarcinoma cell) inhibitory activity,
New way is provided for exploitation cancer therapy drug.
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 adjacent first of di-n-butyl tin
Epoxide nicotinate complex.
The second object of the present invention is to provide the preparation method of above-mentioned di-n-butyl tin O-methoxy nicotinate complex.
The 3rd mesh of the present invention is to provide above-mentioned di-n-butyl tin O-methoxy nicotinate complex and is preparing cancer therapy drug
In application.
As a kind of di-n-butyl tin O-methoxy nicotinate complex of first aspect present invention, it is following structural formula
(I) R represents normal-butyl in complex, formula：
The di-n-butyl tin O-methoxy nicotinate complex of the present invention is through elementary analysis, infrared spectrum analysis, and nuclear-magnetism is common
Spectrum of shaking and x-ray crystal structure analysis, it is as a result as follows：
Elementary analysis (C60H96N4O14Sn4)：Theoretical value：C, 45.83；H, 6.15；N, 3.56.Measured value：C, 45.87；H,
6.10；N, 3.51.
IR(KBr,cm-1):2955,2928,2868v(C-H),1585vas(COO-),1466vs(COO-),573v(Sn-
C),482v(Sn-O)。
1H NMR(CDCl3,500MHz),δ6.94-8.25(m,12H,Ph-H),4.05(s,12H,-OCH3),1.73-
0.81(m,72H,Bu-H)。
13C NMR(CDCl3, 125MHz), δ 13.67,26.83,27.29,27.56 (Bu), 53.63 (- OCH3),
116.32,118.17,140.32,149.18,1161.79 (Ph-C), 171.70 (- COO).
119Sn NMR(CDCl3, 186MHz), -201.96, -206.60, -213.93, -509.24
The di-n-butyl tin O-methoxy nicotinate complex of the present invention is crystal structure, its crystallographic data：Crystal belongs to
Anorthic system, space group, a=1.19070 (8) nm, b=1.23275 (8) nm, c=1.35127 (15) nm, α=
104.4070 (10) °, β=101.1430 (10) °, γ=107.9860 (10) °, Z=1, V=1.7469 (3) nm3, Dc=
1.494Mg·m-3, μ (MoKa)=1.473mm-1, F (000)=796,2.61 ° of 27.61 ° of ＜ θ ＜, crystalline size：
0.23x0.21x0.20mm, R=0.0333, wR=0.0770.
The di-n-butyl tin O-methoxy nicotinate complex of the present invention is structurally characterized in that：Exist in molecule with tin and oxygen
The Sn of atomic building2O2Planar four-element ring, three four-membered rings are that bridgehead atom condenses to form four core tin oxygen clusters using Sn-O keys atom
Trapezium structure, the center of middle ring is the symmetrical centre of molecule, three tin atoms for having two oxygen atom difference bridging ladders in ladder,
It is another to have two terraced tin atoms of oxygen atom difference bridging；Terraced other two O-methoxy nicotinic acid carboxyls be utilized respectively its carboxyl oxygen atom with
The tin atom bonding formation of Sn-O-Sn chains and the hexa-atomic tin oxa- ring structure of its common chain.
As a kind of preparation method of di-n-butyl tin O-methoxy nicotinate complex of second aspect of the present invention, anti-
Answer and sequentially add O-methoxy nicotinic acid, Dibutyltin oxide and etoh solvent in container in order, be 80~90 DEG C in temperature
Under the conditions of react 8~12h；Cooling, filtering controls solvent volatilization crystallization under conditions of 20~35 DEG C, obtains colourless transparent crystal,
As di-n-butyl tin O-methoxy nicotinate complex.
In a preferred embodiment of the invention, the O-methoxy nicotinic acid, the mol ratio of Dibutyltin oxide are 1:
(1~1.05).
In a preferred embodiment of the invention, the etoh solvent consumption is that every mM of Dibutyltin oxide adds 20
~35 milliliters.
Cancer therapy drug is being prepared as a kind of di-n-butyl tin O-methoxy nicotinate complex of third aspect present invention
In application.
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 di-n-butyl tin O-methoxy nicotinate complex of the present invention has certain thermally-stabilised scope, 140 DEG C with
Under can be stabilized.It shows good active anticancer to human lung cancer medicine, human breast carcinoma etc., can be prepared using it as raw material anti-
Lung cancer, anti-breast cancer medicines.Compared with the platinum-containing anticancer drug generally used at present, di-n-butyl tin O-methoxy of the invention
Nicotinate complex has the features such as active anticancer is high, cost is low, preparation method is simple, and new way is provided for exploitation cancer therapy drug
Footpath.
Brief description of the drawings
Fig. 1 is the crystal molecular structure figure of di-n-butyl tin O-methoxy nicotinate complex of the present invention.
Fig. 2 is the IR spectrograms of di-n-butyl tin O-methoxy nicotinate complex of the present invention.
Fig. 3 is di-n-butyl tin O-methoxy nicotinate complex of the present invention1H NMR spectras.
Fig. 4 is di-n-butyl tin O-methoxy nicotinate complex of the present invention13C NMR spectras.
Fig. 5 is di-n-butyl tin O-methoxy nicotinate complex of the present invention119Sn NMR spectras.
Fig. 6 is the TG-DTG curves of di-n-butyl tin O-methoxy nicotinate complex of the present invention.
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 di-n-butyl tin O-methoxy nicotinate complex：
Sequentially add O-methoxy nicotinic acid 0.1534g (1mmol), Dibutyltin oxide in order in 50ml round-bottomed flasks
0.2483g (1mmol), etoh solvent 20mL, 8h is reacted under conditions of temperature is 80~90 DEG C；Cooling, filtering, 20~35
Solvent volatilization crystallization is controlled under conditions of DEG C, colourless transparent crystal, as di-n-butyl tin O-methoxy nicotinate complex is obtained.
Yield：78%, fusing point：85-86℃.
Elementary analysis (C60H96N4O14Sn4)：Theoretical value：C, 45.83；H, 6.15；N, 3.56.Measured value：C, 45.87；H,
6.10；N, 3.51.
IR(KBr,cm-1):2955,2928,2868v(C-H),1585vas(COO-),1466vs(COO-),573v(Sn-
C),482v(Sn-O)。
1H NMR(CDCl3,500MHz),δ6.94-8.25(m,12H,Ph-H),4.05(s,12H,-OCH3),1.73-
0.81(m,72H,Bu-H)。
13C NMR(CDCl3, 125MHz), δ 13.67,26.83,27.29,27.56 (Bu), 53.63 (- OCH3),
116.32,118.17,140.32,149.18,1161.79 (Ph-C), 171.70 (- COO).
119Sn NMR(CDCl3, 186MHz), -201.96, -206.60, -213.93, -509.24
Its crystallographic data：Crystal belongs to anorthic system, space group, a=1.19070 (8) nm, b=1.23275 (8) nm,
C=1.35127 (15) nm, α=104.4070 (10) °, β=101.1430 (10) °, γ=107.9860 (10) °, Z=1, V=
1.7469(3)nm3, Dc=1.494Mgm-3, μ (MoKa)=1.473mm-1, F (000)=796,2.61 ° of 27.61 ° of ＜ θ ＜,
Crystalline size：0.23x0.21x0.20mm, R=0.0333, wR=0.0770.
Embodiment 2：
The preparation of di-n-butyl tin O-methoxy nicotinate complex：
Sequentially add O-methoxy nicotinic acid 0.1536g (1mmol), Dibutyltin oxide in order in 50ml round-bottomed flasks
0.2617g (1.05mmol), etoh solvent 20mL, 8h is reacted under conditions of temperature is 80~90 DEG C；Cooling, filtering, 20
Solvent volatilization crystallization is controlled under conditions of~35 DEG C, colourless transparent crystal is obtained, as di-n-butyl tin O-methoxy nicotinate is matched somebody with somebody
Compound.Yield：76%, fusing point：85-86℃.
Elementary analysis (C60H96N4O14Sn4)：Theoretical value：C, 45.83；H, 6.15；N, 3.56.Measured value：C, 45.87；H,
6.10；N, 3.51.
IR(KBr,cm-1):2955,2928,2868v(C-H),1585vas(COO-),1466vs(COO-),573v(Sn-
C),482v(Sn-O)。
1H NMR(CDCl3,500MHz),δ6.94-8.25(m,12H,Ph-H),4.05(s,12H,-OCH3),1.73-
0.81(m,72H,Bu-H)。
13C NMR(CDCl3, 125MHz), δ 13.67,26.83,27.29,27.56 (Bu), 53.63 (- OCH3),
116.32,118.17,140.32,149.18,1161.79 (Ph-C), 171.70 (- COO).
119Sn NMR(CDCl3, 186MHz), -201.96, -206.60, -213.93, -509.24
Its crystallographic data：Crystal belongs to anorthic system, space group, a=1.19070 (8) nm, b=1.23275 (8) nm,
C=1.35127 (15) nm, α=104.4070 (10) °, β=101.1430 (10) °, γ=107.9860 (10) °, Z=1, V=
1.7469(3)nm3, Dc=1.494Mgm-3, μ (MoKa)=1.473mm-1, F (000)=796,2.61 ° of 27.61 ° of ＜ θ ＜,
Crystalline size：0.23x0.21x0.20mm, R=0.0333, wR=0.0770.
Embodiment 3：
The preparation of di-n-butyl tin O-methoxy nicotinate complex：
Sequentially add O-methoxy nicotinic acid 0.1535g (1mmol), Dibutyltin oxide in order in 50ml round-bottomed flasks
0.2486g (1mmol), etoh solvent 35mL, 8h is reacted under conditions of temperature is 80~90 DEG C；Cooling, filtering, 20~35
Solvent volatilization crystallization is controlled under conditions of DEG C, colourless transparent crystal, as di-n-butyl tin O-methoxy nicotinate complex is obtained.
Yield：78%, fusing point：85-86℃.
Elementary analysis (C60H96N4O14Sn4)：Theoretical value：C, 45.83；H, 6.15；N, 3.56.Measured value：C, 45.87；H,
6.10；N, 3.51.
IR(KBr,cm-1):2955,2928,2868v(C-H),1585vas(COO-),1466vs(COO-),573v(Sn-
C),482v(Sn-O)。
1H NMR(CDCl3,500MHz),δ6.94-8.25(m,12H,Ph-H),4.05(s,12H,-OCH3),1.73-
0.81(m,72H,Bu-H)。
13C NMR(CDCl3, 125MHz), δ 13.67,26.83,27.29,27.56 (Bu), 53.63 (- OCH3),
116.32,118.17,140.32,149.18,1161.79 (Ph-C), 171.70 (- COO).
119Sn NMR(CDCl3, 186MHz), -201.96, -206.60, -213.93, -509.24
Its crystallographic data：Crystal belongs to anorthic system, space group, a=1.19070 (8) nm, b=1.23275 (8) nm,
C=1.35127 (15) nm, α=104.4070 (10) °, β=101.1430 (10) °, γ=107.9860 (10) °, Z=1, V=
1.7469(3)nm3, Dc=1.494Mgm-3, μ (MoKa)=1.473mm-1, F (000)=796,2.61 ° of 27.61 ° of ＜ θ ＜,
Crystalline size：0.23x0.21x0.20mm, R=0.0333, wR=0.0770.
Embodiment 4：
The preparation of di-n-butyl tin O-methoxy nicotinate complex：
Sequentially add O-methoxy nicotinic acid 0.1538g (1mmol), Dibutyltin oxide in order in 50ml round-bottomed flasks
0.2487g (1mmol), etoh solvent 20mL, 10h is reacted under conditions of temperature is 80~90 DEG C；Cooling, filtering, 20~
Solvent volatilization crystallization is controlled under conditions of 35 DEG C, colourless transparent crystal is obtained, as di-n-butyl tin O-methoxy nicotinate coordinates
Thing.Yield：80%, fusing point：85-86℃.
Elementary analysis (C60H96N4O14Sn4)：Theoretical value：C, 45.83；H, 6.15；N, 3.56.Measured value：C, 45.87；H,
6.10；N, 3.51.
IR(KBr,cm-1):2955,2928,2868v(C-H),1585vas(COO-),1466vs(COO-),573v(Sn-
C),482v(Sn-O)。
1H NMR(CDCl3,500MHz),δ6.94-8.25(m,12H,Ph-H),4.05(s,12H,-OCH3),1.73-
0.81(m,72H,Bu-H)。
13C NMR(CDCl3, 125MHz), δ 13.67,26.83,27.29,27.56 (Bu), 53.63 (- OCH3),
116.32,118.17,140.32,149.18,1161.79 (Ph-C), 171.70 (- COO).
119Sn NMR(CDCl3, 186MHz), -201.96, -206.60, -213.93, -509.24
Its crystallographic data：Crystal belongs to anorthic system, space group, a=1.19070 (8) nm, b=1.23275 (8) nm,
C=1.35127 (15) nm, α=104.4070 (10) °, β=101.1430 (10) °, γ=107.9860 (10) °, Z=1, V=
1.7469(3)nm3, Dc=1.494Mgm-3, μ (MoKa)=1.473mm-1, F (000)=796,2.61 ° of 27.61 ° of ＜ θ ＜,
Crystalline size：0.23x0.21x0.20mm, R=0.0333, wR=0.0770.
Embodiment 5：
The preparation of di-n-butyl tin O-methoxy nicotinate complex：
Sequentially add O-methoxy nicotinic acid 0.1535g (1mmol), Dibutyltin oxide in order in 50ml round-bottomed flasks
0.2484g (1mmol), etoh solvent 20mL, 12h is reacted under conditions of temperature is 80~90 DEG C；Cooling, filtering, 20~
Solvent volatilization crystallization is controlled under conditions of 35 DEG C, colourless transparent crystal is obtained, as di-n-butyl tin O-methoxy nicotinate coordinates
Thing.Yield：80%, fusing point：85-86℃.
Elementary analysis (C60H96N4O14Sn4)：Theoretical value：C, 45.83；H, 6.15；N, 3.56.Measured value：C, 45.87；H,
6.10；N, 3.51.
IR(KBr,cm-1):2955,2928,2868v(C-H),1585vas(COO-),1466vs(COO-),573v(Sn-
C),482v(Sn-O)。
1H NMR(CDCl3,500MHz),δ6.94-8.25(m,12H,Ph-H),4.05(s,12H,-OCH3),1.73-
0.81(m,72H,Bu-H)。
13C NMR(CDCl3, 125MHz), δ 13.67,26.83,27.29,27.56 (Bu), 53.63 (- OCH3),
116.32,118.17,140.32,149.18,1161.79 (Ph-C), 171.70 (- COO).
119Sn NMR(CDCl3, 186MHz), -201.96, -206.60, -213.93, -509.24
Its crystallographic data：Crystal belongs to anorthic system, space group, a=1.19070 (8) nm, b=1.23275 (8) nm,
C=1.35127 (15) nm, α=104.4070 (10) °, β=101.1430 (10) °, γ=107.9860 (10) °, Z=1, V=
1.7469(3)nm3, Dc=1.494Mgm-3, μ (MoKa)=1.473mm-1, F (000)=796,2.61 ° of 27.61 ° of ＜ θ ＜,
Crystalline size：0.23x0.21x0.20mm, R=0.0333, wR=0.0770.
Embodiment 6：
The preparation of di-n-butyl tin O-methoxy nicotinate complex：
Sequentially add O-methoxy nicotinic acid 0.3062g (2mmol), Dibutyltin oxide in order in 50ml round-bottomed flasks
0.4980g (2mmol), etoh solvent 40mL, 10h is reacted under conditions of temperature is 80~90 DEG C；Cooling, filtering, 20~
Solvent volatilization crystallization is controlled under conditions of 35 DEG C, colourless transparent crystal is obtained, as di-n-butyl tin O-methoxy nicotinate coordinates
Thing.Yield：76%, fusing point：85-86℃.
Elementary analysis (C60H96N4O14Sn4)：Theoretical value：C, 45.83；H, 6.15；N, 3.56.Measured value：C, 45.87；H,
6.10；N, 3.51.
IR(KBr,cm-1):2955,2928,2868v(C-H),1585vas(COO-),1466vs(COO-),573v(Sn-
C),482v(Sn-O)。
1H NMR(CDCl3,500MHz),δ6.94-8.25(m,12H,Ph-H),4.05(s,12H,-OCH3),1.73-
0.81(m,72H,Bu-H)。
13C NMR(CDCl3, 125MHz), δ 13.67,26.83,27.29,27.56 (Bu), 53.63 (- OCH3),
116.32,118.17,140.32,149.18,1161.79 (Ph-C), 171.70 (- COO).
119Sn NMR(CDCl3, 186MHz), -201.96, -206.60, -213.93, -509.24
Its crystallographic data：Crystal belongs to anorthic system, space group, a=1.19070 (8) nm, b=1.23275 (8) nm,
C=1.35127 (15) nm, α=104.4070 (10) °, β=101.1430 (10) °, γ=107.9860 (10) °, Z=1, V=
1.7469(3)nm3, Dc=1.494Mgm-3, μ (MoKa)=1.473mm-1, F (000)=796,2.61 ° of 27.61 ° of ＜ θ ＜,
Crystalline size：0.23x0.21x0.20mm, R=0.0333, wR=0.0770.
Test example：
The di-n-butyl tin O-methoxy nicotinate complex of the present invention, it is real by MTT that its Anticancer Activity in vitro, which is determined,
What proved recipe 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 di-n-butyl tin O-methoxy nicotinate complex that the preparation of embodiment 1 is determined using mtt assay is thin to human lung cancer
Born of the same parents (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 di-n-butyl tin O-methoxy nicotinate complex of invention is higher to human lung cancer, human breast carcinoma activity as cancer therapy drug, can
It is used as the candidate compound of cancer therapy drug.
The di-n-butyl tin O-methoxy nicotinate 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 | 4.41 | 3.51 | 7.08 |
Di-n-butyl tin O-methoxy nicotinate 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), is surveyed
Test result and table 1 are essentially identical.
Claims (8)
1. a kind of di-n-butyl tin O-methoxy nicotinate complex, it is characterised in that be the complex of following structure formula (I)：
R represents butyl in formula.
2. contain a kind of di-n-butyl tin O-methoxy nicotinate complex, its ir data as claimed in claim 1：
FT-IR(KBr,v/cm-1):2955,2928,2868v(C-H),1585vas(COO-),1466vs(COO-),573v(Sn-C),
482v(Sn-O)。
3. di-n-butyl tin O-methoxy nicotinate complex as claimed in claim 1, wherein, described di-n-butyl tin is adjacent
Methoxyl group nicotinate complex is crystal structure, and its crystallographic data is as follows：Anorthic system, space groupA=1.19070
(8) nm, b=1.23275 (8) nm, c=1.35127 (15) nm, α=104.4070 (10) °, β=101.1430 (10) °, γ=
107.9860 (10) °, Z=1, V=1.7469 (3) nm3, there is the Sn constituted with tin and oxygen atom in molecule2O2Planar four-element
Ring, three four-membered rings are that bridgehead atom condenses to form four core tin oxygen cluster trapezium structures, the center of middle ring using Sn-O keys atom
For the symmetrical centre of molecule, there are three tin atoms of two oxygen atoms difference bridging ladders in ladder, separately there are two oxygen atoms to distinguish bridges
The terraced tin atom of connection；Terraced other two O-methoxy nicotinic acid carboxyls be utilized respectively the tin atom of its carboxyl oxygen atom and Sn-O-Sn chains into
Key formation and the hexa-atomic tin oxa- ring structure of its common chain.
4. the preparation side of the di-n-butyl tin O-methoxy nicotinate complex described in any one of claims 1 to 3 claim
Method, it is characterised in that sequentially add O-methoxy nicotinic acid, Dibutyltin oxide and etoh solvent in order in reaction vessel,
8~12h is reacted under conditions of temperature is 80~90 DEG C；Cooling, filtering controls solvent volatilization knot under conditions of 20~35 DEG C
Crystalline substance, obtains colourless transparent crystal, as di-n-butyl tin O-methoxy nicotinate complex.
5. preparation method as claimed in claim 4, it is characterised in that the O-methoxy nicotinic acid, Dibutyltin oxide rub
You are than being 1:(1~1.05).
6. preparation method as claimed in claim 4, it is characterised in that the etoh solvent consumption is every mM of dibutyl oxygen
Change tin add 20~35 milliliters.
7. di-n-butyl tin O-methoxy nicotinate complex described in any one of claims 1 to 3 claim is preparing treatment
Application in cancer drug.
8. the application described in claim 7, wherein the cancer is lung cancer or breast cancer.
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Non-Patent Citations (4)
| Title |
|---|
| ANTHONY LINDEN等: "Tetrakis(μ2-4-aminobenzoato)di-μ3-oxido-tetrakis[dibutyltin(IV)]", 《ACTA CRYSTALLOGRAPHICA SECTION C》 * |
| IRÁN FERNANDO HERNÁNDEZ-AHUACTZI等: "Tuning the Supramolecular Structure through Variation of the Ligand Geometry and Metal Substituents−Diorganotin Macrocycles …… cis- and trans-1,2‑, 1,3‑, and 1,4-Cyclohexanedicarboxylic and cis,cis-1,3,5-Cyclohexanetricarboxylic Acid", 《CRYST. GROWTH DES.》 * |
| MIN HONG等: "Bis(μ-3-nitrobenzoato)-1:2κ2O:O＇;3:4κ2O:O＇-bis(3-nitrobenzoato)-1κ2O,O＇;3κ2O,O＇-di-μ3-oxo-1:2:4κ3O;2:3:4κ3O-tetrakis[di-n-butyltin(IV)]", 《ACTA CRYSTALLOGRAPHICA SECTION E》 * |
| 尹汉东等: "有机锡化合物二{氧合-二[ 杂环羧酸二丁基锡(IV)] }的合成、表征和二{氧合-二[ 2-噻吩甲酸二丁基锡(IV)] }的晶体结构", 《有机化学》 * |
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