CN106220670B - Two pairs of methylbenzyl tin complexs of one kind and its preparation method and application - Google Patents
Two pairs of methylbenzyl tin complexs of one kind and its preparation method and application Download PDFInfo
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- CN106220670B CN106220670B CN201610712384.9A CN201610712384A CN106220670B CN 106220670 B CN106220670 B CN 106220670B CN 201610712384 A CN201610712384 A CN 201610712384A CN 106220670 B CN106220670 B CN 106220670B
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- VRJDPZSIONEOLJ-UHFFFAOYSA-N benzyl(methyl)tin Chemical compound C[Sn]CC1=CC=CC=C1 VRJDPZSIONEOLJ-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- -1 phenylpropionic acid p-nitrophenyl formyl hydrazone Chemical compound 0.000 claims abstract description 31
- 125000006178 methyl benzyl group Chemical group 0.000 claims abstract description 13
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 10
- 229940041181 antineoplastic drug Drugs 0.000 claims abstract description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 claims description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 229910052718 tin Inorganic materials 0.000 claims description 17
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical group [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 206010006187 Breast cancer Diseases 0.000 claims description 11
- 208000026310 Breast neoplasm Diseases 0.000 claims description 11
- 239000013078 crystal Substances 0.000 claims description 11
- 201000007270 liver cancer Diseases 0.000 claims description 11
- 208000014018 liver neoplasm Diseases 0.000 claims description 11
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 9
- FKZXYJYTUSGIQE-UHFFFAOYSA-N 4-nitrobenzohydrazide Chemical compound NNC(=O)C1=CC=C([N+]([O-])=O)C=C1 FKZXYJYTUSGIQE-UHFFFAOYSA-N 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 229910021626 Tin(II) chloride Inorganic materials 0.000 claims description 7
- 235000011150 stannous chloride Nutrition 0.000 claims description 7
- 239000001119 stannous chloride Substances 0.000 claims description 7
- 238000000902 119Sn nuclear magnetic resonance spectroscopy Methods 0.000 claims description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 claims description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 claims description 6
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 201000005296 lung carcinoma Diseases 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 238000002425 crystallisation Methods 0.000 claims description 5
- 230000008025 crystallization Effects 0.000 claims description 5
- 238000002447 crystallographic data Methods 0.000 claims description 5
- MQGYVGKMCRDEAF-UHFFFAOYSA-M sodium;2-oxo-3-phenylpropanoate Chemical compound [Na+].[O-]C(=O)C(=O)CC1=CC=CC=C1 MQGYVGKMCRDEAF-UHFFFAOYSA-M 0.000 claims description 4
- XZBIXDPGRMLSTC-UHFFFAOYSA-N formohydrazide Chemical compound NNC=O XZBIXDPGRMLSTC-UHFFFAOYSA-N 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- 230000005311 nuclear magnetism Effects 0.000 claims 1
- 238000004611 spectroscopical analysis Methods 0.000 claims 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 abstract 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract 2
- 210000004027 cell Anatomy 0.000 description 38
- 230000001093 anti-cancer Effects 0.000 description 13
- 238000012360 testing method Methods 0.000 description 12
- 239000003814 drug Substances 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 238000011160 research Methods 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- 229940079593 drug Drugs 0.000 description 6
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 238000000921 elemental analysis Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 206010009944 Colon cancer Diseases 0.000 description 4
- 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 description 4
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 201000005249 lung adenocarcinoma Diseases 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 239000002262 Schiff base Substances 0.000 description 3
- 150000004753 Schiff bases Chemical class 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 125000002524 organometallic group Chemical group 0.000 description 3
- 241000254173 Coleoptera Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 201000008275 breast carcinoma Diseases 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification 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
- 230000003287 optical effect Effects 0.000 description 2
- 125000000962 organic group Chemical group 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
- 238000012216 screening Methods 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
- FTZIQBGFCYJWKA-UHFFFAOYSA-N 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Chemical compound S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 FTZIQBGFCYJWKA-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- NSZRQCQXHMPQEY-UHFFFAOYSA-N C(=O)=C(C(=O)O)CC1=CC=CC=C1 Chemical class C(=O)=C(C(=O)O)CC1=CC=CC=C1 NSZRQCQXHMPQEY-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 229910020813 Sn-C Inorganic materials 0.000 description 1
- 229910018732 Sn—C Inorganic materials 0.000 description 1
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- WARCRYXKINZHGQ-UHFFFAOYSA-N benzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1 WARCRYXKINZHGQ-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- YAYRGNWWLMLWJE-UHFFFAOYSA-L carboplatin Chemical compound O=C1O[Pt](N)(N)OC(=O)C11CCC1 YAYRGNWWLMLWJE-UHFFFAOYSA-L 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- AYOHIQLKSOJJQH-UHFFFAOYSA-N dibutyltin Chemical compound CCCC[Sn]CCCC AYOHIQLKSOJJQH-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- WDQNIWFZKXZFAY-UHFFFAOYSA-M fentin acetate Chemical compound CC([O-])=O.C1=CC=CC=C1[Sn+](C=1C=CC=CC=1)C1=CC=CC=C1 WDQNIWFZKXZFAY-UHFFFAOYSA-M 0.000 description 1
- NJVOZLGKTAPUTQ-UHFFFAOYSA-M fentin chloride Chemical compound C=1C=CC=CC=1[Sn](C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 NJVOZLGKTAPUTQ-UHFFFAOYSA-M 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003606 tin compounds Chemical class 0.000 description 1
- XOLBLPGZBRYERU-UHFFFAOYSA-N tin dioxide Chemical compound O=[Sn]=O XOLBLPGZBRYERU-UHFFFAOYSA-N 0.000 description 1
- 229910001887 tin oxide Inorganic materials 0.000 description 1
- CVNKFOIOZXAFBO-UHFFFAOYSA-J tin(4+);tetrahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[Sn+4] CVNKFOIOZXAFBO-UHFFFAOYSA-J 0.000 description 1
- QHGNHLZPVBIIPX-UHFFFAOYSA-N tin(ii) oxide Chemical compound [Sn]=O QHGNHLZPVBIIPX-UHFFFAOYSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 210000003462 vein Anatomy 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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of 2 carbonyl, 3 phenylpropionic acid p-nitrophenyl formyl hydrazones two to methylbenzyl tin complex, is the complex of following structure formula (I), wherein Ph is phenyl, and R is to methylbenzyl.The invention also discloses 2 carbonyl, 3 preparation method of the phenylpropionic acid p-nitrophenyl formyl hydrazone two to methylbenzyl tin complex and the applications in preparing anticancer drug.
Description
Technical field
The present invention relates to a kind of 2- carbonyls -3- phenylpropionic acid p-nitrophenyls formyl hydrazones two to methylbenzyl tin complex and its
Preparation method and the 2- carbonyl -3- phenylpropionic acid p-nitrophenyls formyl hydrazone two are preparing anticancer to methylbenzyl tin complex
Application in drug.
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.The research of organotin (IV) antitumor activity of compound can trace back to nineteen twenty-nine.
1967, Kanisawa etc. thought that stannic chloride is invalid to the primary tumor of mouse and rat.But in 1972, Brown had found,
Pass through food or drug administration by injection, triphenyltin acetate Ph3SnOOCCH3It can inhibit the tumour growth of mouse, and triphenyltin chloride
Then cannot.Between 1972 ~ 1977 years, Dutch scholar has studied a large amount of organo-tin compound, but finds no further screening valence
The compound of value.They continue deeper into research, finally found that the tin compound of two organic groups coordination, such as tin-oxide
(R2SnO), tin hydroxide ［ SnR2(OH) X ］ etc. have antitumor activity, and find out that they all contain or hydrolyze and can generate tin oxygen
Key.1980, Crowe etc. was found that some organo-tin compounds have preferable active anticancer again, anti-about organotin from this
The active research of cancer becomes the another extremely active hot spot after cis-platinum.1989, American National anticancer research institute
(National Cancer Institute) has carried out antitumor activity screening to more than 2,000 kinds of organo-tin compounds, as a result table
Some bright organo-tin compounds have inhibiting effect to P388 lymphocytic leukemias.2002, Gielen et al. was to organic
The activity of tin carboxylate compound has done comprehensive summing up, and many organo-tin compounds are thought after research really has preferably in vitro
Active anticancer.
Studies have shown that the organic group connected on organic tin atom and the ligand for participating in being coordinated decide organo-tin compound
Bioactivity, select some itself have the active organic ligand of good biological in organotin tin atom be coordinated cause
The great interest of people.Acylhydrazone is a kind of Schiff compound made of being modified by hydrazide kind compound, they
It is condensed by aldehydes or ketones and hydrazides, there is the bond type similar with peptide bond in molecule, there is good bioactivity, stronger match
Capability and various coordination mode, and have a wide range of applications in medicine, pesticide, material and analytical reagent etc..Closely
Nian Lai, domestic and international many researchers compare it in terms of bioactivity in depth to be studied, and research finds acylhydrazone class
Compound has the various actives such as anticancer, sterilization, anti-inflammatory.Therefore, acylhydrazone class Schiff ligand is combined with organotin, it is intended to
The stronger noval chemical compound of bioactivity is obtained, the interested research direction of people is become.
Chinese patent CN 102718794A disclose a kind of double acylhydrazone class Schiff stannous phenide complexs and its are making
Standby Antilung gland cancer, colon cancer, leukaemia cell drug in application.
Chinese patent CN 101851251A disclose a kind of acylhydrazone class Schiff ligand dibutyl tin complex and its
Application in the drug 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:It 83-91) reports, organotin
Acylhydrazone class Schiff base complex is thin to human colon cancer cell (HCT-116), human lung adenocarcinoma cell (A549), human umblilical vein endothelial
Born of the same parents (HUVEC) have compared with strong biological activity, and are better than carboplatin.
Document (Journal of Organometallic Chemistry, 2013,724:It 23-31) reports, series has
Machine tin acylhydrazone class Schiff base complex, organo-tin compound and acylhydrazone class Schiff ligand are respectively to human lung adenocarcinoma cell
(A549), the inhibiting effect of the cancer cells such as human colon cancer cell (HCT-8), people in loop (hl-60).
Document (Bioorganic ＆ Medicinal Chemistry Letters, 2015,25: 4461- 4463)
Report, active anticancer of a variety of acylhydrazone class Schiff ligands to human liver cancer cell (HuH-7) and human lung adenocarcinoma cell (A549).
Document (Journal of Organometallic Chemistry, 2016,804:It 48-58) reports, two hydrocarbon
Base tin acylhydrazone class Schiff base complex is to human lung adenocarcinoma cell (A549), human cervical carcinoma cell (HeLa), human breast cancer cell
(MCF-7) inhibiting effect of cancer cells such as.
It is the experiment proved that the substance with active anticancer, present invention choosing based on acylhydrazone class Schiff organotin complex
Select p-nitrobenzoylhydrazide, Sodium.beta.-phenylpyruvate reacts under certain condition with two pairs of methylbenzyl stannous chloride, synthesis obtain
There is certain inhibitory activity to match human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7)
Object is closed, new approach is provided for exploitation anticancer drug.
Invention content
There is provided a kind of 2- carbonyls -3- phenylpropionic acid p-nitrophenyls formyl hydrazones two to methyl benzyl for the first object of the present invention
Base tin complex.
The second object of the present invention is to provide above-mentioned 2- carbonyls -3- phenylpropionic acid p-nitrophenyl formyl hydrazones two to methylbenzyl
Tin complex preparation method.
The third object of the present invention is to provide above-mentioned 2- carbonyls -3- phenylpropionic acid p-nitrophenyl formyl hydrazones two to methylbenzyl
Application of the tin complex in preparing anticancer drug.
A kind of 2- carbonyls -3- phenylpropionic acid p-nitrophenyl formyl hydrazones two as the first aspect of the present invention are to methylbenzyl
Tin complex is the complex of structure formula (I)
(I)
Wherein Ph is phenyl, and R is to methylbenzyl tin.
2- carbonyl -3- phenylpropionic acid p-nitrophenyls the formyl hydrazone two of the present invention is to methylbenzyl tin complex through element point
Analysis, infrared spectrum, nuclear magnetic resoance spectrum and X-ray single crystal diffraction structural analysis, it is as a result as follows：
Elemental analysis (C66H66N6O12Sn2)：Calculated value：C 57.75, H 4.85, N 6.12；Measured value：C 57.80, H
4.84, N 6.11.
FT-IR (KBr, ν/cm-1): 3566, 3022, 2918, 2860, 1637, 1618, 1597, 1525,
1492, 1386, 1338, 1317, 1226, 1170, 1134, 1105, 1014, 894, 858, 815, 758,
711, 588, 561, 505, 459, 418。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.30 (d, J =8.8 Hz, 2H), 8.09 (d, J =
8.8 Hz, 2H), 7.38 (d, J =7.7 Hz, 2H), 7.33 (t, J =7.7 Hz, 2H), 7.28 (d, J =
7.2 Hz, 1H), 6.67 (d, J =7.9 Hz, 4H), 6.62(d, J =7.9 Hz, 4H), 3.91 (s, 2H),
3.18 (d, J =11.7 Hz, 2H), 3.12 (d, J =11.7 Hz, 2H), 2.08 (s, 6H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 172.94, 168.64, 153.45, 149.85,
139.11, 134.94, 134.80, 132.94, 129.91, 129.66, 128.88, 128.56, 128.12,
126.99, 123.20, 50.86, 36.66, 32.39, 20.87。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -636.93。
2- carbonyl -3- phenylpropionic acid p-nitrophenyls the formyl hydrazone two of the present invention is crystal knot to methylbenzyl tin complex
Structure, crystal be monoclinic system, space group P2 (1)/n, a=1.6255 (2) nm, b=1.20419 (17) nm, c=
1.7800 (2) nm, α=γ=90 °, β=112.560 (4) °, Z=4, V=3.2175 (8) nm3, the Mgm of Dc=1.417-3, m (MoK α)=0.841 mm-1, F (000)=1400.
Design feature of the 2- carbonyl -3- phenylpropionic acid p-nitrophenyls formyl hydrazone two of the present invention to methylbenzyl tin complex
It is：Tin atom is seven coordination distortion pentagonal bipyramid configurations in molecule.
2- carbonyl -3- phenylpropionic acid p-nitrophenyls the formyl hydrazone two of the present invention has centainly methylbenzyl tin complex
Thermostabilization range can be stabilized at 86 DEG C or less.
A kind of 2- carbonyls -3- phenylpropionic acid p-nitrophenyl formyl hydrazones two as the second aspect of the present invention are to methylbenzyl
Two pairs of methylbenzyl stannous chloride, p-nitrophenyls are added in the preparation method of tin complex in the reaction vessel for having nitrogen protection
Formylhydrazine, Sodium.beta.-phenylpyruvate and solvent absolute methanol react 5 ~ 20 h under conditions of temperature is 50 ~ 65 DEG C, cooling, filtering,
Solvent volatilization crystallization is controlled under conditions of 20 ~ 35 DEG C, obtains yellow transparent crystal, as 2- carbonyls -3- phenylpropionic acids are to nitro
Benzoyl hydrazone two is to methylbenzyl tin complex.
Preparation characteristic of the 2- carbonyl -3- phenylpropionic acid p-nitrophenyls formyl hydrazone two of the present invention to methylbenzyl tin complex
It is：Complicated molecule, i.e. one kettle way are directly obtained from raw material relatively simple and easy to get without the separation of intermediate；
It is such to react on economically and environmentally close friend advantageously.
In a preferred embodiment of the invention, two pairs of methylbenzyl stannous chloride, p-nitrobenzoylhydrazide, benzene
The amount ratio of the substance of Sodium Pyruvate three is 1:(1~1.05):(1.05~1.15).
In a preferred embodiment of the invention, the solvent absolute methanol dosage is every mM of two pairs of methylbenzyls
Stannous chloride adds 15 ~ 35 milliliters.
A kind of 2- carbonyls -3- phenylpropionic acid p-nitrophenyl formyl hydrazones two as the third aspect of the present invention are to methylbenzyl
Application of the tin complex in preparing anticancer drug.
Applicant carries out methylbenzyl tin complex above-mentioned 2- carbonyls -3- phenylpropionic acid p-nitrophenyls formyl hydrazone two
Anticancer Activity in vitro determines research, it is thus identified that 2- carbonyl -3- phenylpropionic acid p-nitrophenyls formyl hydrazone two coordinates methylbenzyl tin
Object has certain anticancer bioactive, that is to say, that the purposes of above-mentioned complex is the application in preparing anticancer drug, tool
Saying for body is exactly the application in preparing anti-human lung cancer, human liver cancer and human breast carcinoma drug.
2- carbonyl -3- phenylpropionic acid p-nitrophenyls the formyl hydrazones two of the present invention are thin to human lung cancer to methylbenzyl tin complex
Born of the same parents, human liver cancer cell and human breast cancer cell show good active anticancer, and 2- carbonyl -3- phenylpropionic acids of the invention are to nitre
The features such as base benzoyl hydrazone two is high, at low cost, preparation method is simple to methylbenzyl tin complex active anticancer, to develop newly
Anticancer drug provides new way.
Description of the drawings
Fig. 1 is IR spectrogram of the 2- carbonyl -3- phenylpropionic acid p-nitrophenyls formyl hydrazone two to methylbenzyl tin complex.
Fig. 2 is 2- carbonyl -3- phenylpropionic acid p-nitrophenyls formyl hydrazones two to methylbenzyl tin complex1H NMR spectras.
Fig. 3 is 2- carbonyl -3- phenylpropionic acid p-nitrophenyls formyl hydrazones two to methylbenzyl tin complex13C NMR spectras.
Fig. 4 is 2- carbonyl -3- phenylpropionic acid p-nitrophenyls formyl hydrazones two to methylbenzyl tin complex119Sn H NMR spectroscopies
Figure.
Fig. 5 is crystal structure figure of the 2- carbonyl -3- phenylpropionic acid p-nitrophenyls formyl hydrazone two to methylbenzyl tin complex.
Fig. 6 is TG-DTG curve of the 2- carbonyl -3- phenylpropionic acid p-nitrophenyls formyl hydrazone two to methylbenzyl tin complex.
Specific implementation mode
By detailed description below, invention is further described in detail.
Embodiment 1：
Preparation of the 2- carbonyl -3- phenylpropionic acid p-nitrophenyls formyl hydrazones two to methylbenzyl tin complex：
0.400g (1.0mmol) two pairs of methylbenzyl dichlorides are added in the 100mL three-necked flasks for having nitrogen protection
Tin, 0.181g (1.0mmol) p-nitrobenzoylhydrazide, 0.195g (1.05mmol) Sodium.beta.-phenylpyruvates and 15mL solvents are without water beetle
Alcohol reacts 8 h under conditions of temperature is 50 ~ 65 DEG C, cooling, filtering, and solvent volatilization knot is controlled under conditions of 20 ~ 35 DEG C
Crystalline substance obtains yellow transparent crystal, and as 2- carbonyls -3- phenylpropionic acid p-nitrophenyls formyl hydrazone two is to methylbenzyl tin complex.Production
Rate：70.6%.Fusing point：86~88℃(dec).
Elemental analysis (C66H66N6O12Sn2)：Calculated value：C 57.75, H 4.85, N 6.12；Measured value：C 57.80, H
4.84, N 6.11.
FT-IR (KBr, ν/cm-1): 3566, 3022, 2918, 2860, 1637, 1618, 1597, 1525,
1492, 1386, 1338, 1317, 1226, 1170, 1134, 1105, 1014, 894, 858, 815, 758,
711, 588, 561, 505, 459, 418。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.30 (d, J =8.8 Hz, 2H), 8.09 (d, J =
8.8 Hz, 2H), 7.38 (d, J =7.7 Hz, 2H), 7.33 (t, J =7.7 Hz, 2H), 7.28 (d, J =
7.2 Hz, 1H), 6.67 (d, J =7.9 Hz, 4H), 6.62(d, J =7.9 Hz, 4H), 3.91 (s, 2H),
3.18 (d, J =11.7 Hz, 2H), 3.12 (d, J =11.7 Hz, 2H), 2.08 (s, 6H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 172.94, 168.64, 153.45, 149.85,
139.11, 134.94, 134.80, 132.94, 129.91, 129.66, 128.88, 128.56, 128.12,
126.99, 123.20, 50.86, 36.66, 32.39, 20.87。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -636.93。
Crystallographic data：Monoclinic system, space group P2 (1)/n, a=1.6255 (2) nm, b=1.20419 (17) nm,
C=1.7800 (2) nm, α=γ=90 °, β=112.560 (4) °, Z=4, V=3.2175 (8) nm3, Dc=1.417
Mg·m-3, m (MoK α)=0.841 mm-1, F (000)=1400.
Embodiment 2：
Preparation of the 2- carbonyl -3- phenylpropionic acid p-nitrophenyls formyl hydrazones two to methylbenzyl tin complex：
0.400g (1.0mmol) two pairs of methylbenzyl dichlorides are added in the 100mL three-necked flasks for having nitrogen protection
Tin, 0.190g (1.05mmol) p-nitrobenzoylhydrazide, 0.214g (1.15mmol) Sodium.beta.-phenylpyruvates and 35mL solvents are anhydrous
Methanol reacts 5 h under conditions of temperature is 50 ~ 65 DEG C, cooling, filtering, and solvent volatilization knot is controlled under conditions of 20 ~ 35 DEG C
Crystalline substance obtains yellow transparent crystal, and as 2- carbonyls -3- phenylpropionic acid p-nitrophenyls formyl hydrazone two is to methylbenzyl tin complex.Production
Rate：73.3%.Fusing point：86~88℃(dec).
Elemental analysis (C66H66N6O12Sn2)：Calculated value：C 57.75, H 4.85, N 6.12；Measured value：C 57.80, H
4.84, N 6.11.
FT-IR (KBr, ν/cm-1): 3566, 3022, 2918, 2860, 1637, 1618, 1597, 1525,
1492, 1386, 1338, 1317, 1226, 1170, 1134, 1105, 1014, 894, 858, 815, 758,
711, 588, 561, 505, 459, 418。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.30 (d, J =8.8 Hz, 2H), 8.09 (d, J =
8.8 Hz, 2H), 7.38 (d, J =7.7 Hz, 2H), 7.33 (t, J =7.7 Hz, 2H), 7.28 (d, J =
7.2 Hz, 1H), 6.67 (d, J =7.9 Hz, 4H), 6.62(d, J =7.9 Hz, 4H), 3.91 (s, 2H),
3.18 (d, J =11.7 Hz, 2H), 3.12 (d, J =11.7 Hz, 2H), 2.08 (s, 6H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 172.94, 168.64, 153.45, 149.85,
139.11, 134.94, 134.80, 132.94, 129.91, 129.66, 128.88, 128.56, 128.12,
126.99, 123.20, 50.86, 36.66, 32.39, 20.87。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -636.93。
Crystallographic data：Monoclinic system, space group P2 (1)/n, a=1.6255 (2) nm, b=1.20419 (17) nm,
C=1.7800 (2) nm, α=γ=90 °, β=112.560 (4) °, Z=4, V=3.2175 (8) nm3, Dc=1.417
Mg·m-3, m (MoK α)=0.841 mm-1, F (000)=1400.
Embodiment 3：
Preparation of the 2- carbonyl -3- phenylpropionic acid p-nitrophenyls formyl hydrazones two to methylbenzyl tin complex：
2.000g (5.0mmol) two pairs of methylbenzyl dichlorides are added in the 100mL three-necked flasks for having nitrogen protection
Tin, 0.923g (5.1mmol) p-nitrobenzoylhydrazide, 1.023g (5.5mmol) Sodium.beta.-phenylpyruvates and 25mL solvents are without water beetle
Alcohol reacts 20 h under conditions of temperature is 50 ~ 65 DEG C, cooling, filtering, and solvent volatilization knot is controlled under conditions of 20 ~ 35 DEG C
Crystalline substance obtains yellow transparent crystal, and as 2- carbonyls -3- phenylpropionic acid p-nitrophenyls formyl hydrazone two is to methylbenzyl tin complex.Production
Rate：74.5%.Fusing point：86~88℃(dec).
Elemental analysis (C66H66N6O12Sn2)：Calculated value：C 57.75, H 4.85, N 6.12；Measured value：C 57.80, H
4.84, N 6.11.
FT-IR (KBr, ν/cm-1): 3566, 3022, 2918, 2860, 1637, 1618, 1597, 1525,
1492, 1386, 1338, 1317, 1226, 1170, 1134, 1105, 1014, 894, 858, 815, 758,
711, 588, 561, 505, 459, 418。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.30 (d, J =8.8 Hz, 2H), 8.09 (d, J =
8.8 Hz, 2H), 7.38 (d, J =7.7 Hz, 2H), 7.33 (t, J =7.7 Hz, 2H), 7.28 (d, J =
7.2 Hz, 1H), 6.67 (d, J =7.9 Hz, 4H), 6.62(d, J =7.9 Hz, 4H), 3.91 (s, 2H),
3.18 (d, J =11.7 Hz, 2H), 3.12 (d, J =11.7 Hz, 2H), 2.08 (s, 6H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 172.94, 168.64, 153.45, 149.85,
139.11, 134.94, 134.80, 132.94, 129.91, 129.66, 128.88, 128.56, 128.12,
126.99, 123.20, 50.86, 36.66, 32.39, 20.87。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -636.93。
Crystallographic data：Monoclinic system, space group P2 (1)/n, a=1.6255 (2) nm, b=1.20419 (17) nm,
C=1.7800 (2) nm, α=γ=90 °, β=112.560 (4) °, Z=4, V=3.2175 (8) nm3, Dc=1.417
Mg·m-3, m (MoK α)=0.841 mm-1, F (000)=1400.
Embodiment 4：
Preparation of the 2- carbonyl -3- phenylpropionic acid p-nitrophenyls formyl hydrazones two to methylbenzyl tin complex：
4.000g (10.0mmol) two pairs of methylbenzyl dichlorides are added in the 500mL three-necked flasks for having nitrogen protection
Tin, 1.864g (10.3mmol) p-nitrobenzoylhydrazide, 2.046g (11.0mmol) Sodium.beta.-phenylpyruvates and 200mL solvents are anhydrous
Methanol reacts 16 h under conditions of temperature is 50 ~ 65 DEG C, cooling, filtering, and solvent volatilization is controlled under conditions of 20 ~ 35 DEG C
Crystallization, obtains yellow transparent crystal, as 2- carbonyls -3- phenylpropionic acid p-nitrophenyls formyl hydrazone two is to methylbenzyl tin complex.
Yield：72.1%.Fusing point：86~88℃(dec).
Elemental analysis (C66H66N6O12Sn2)：Calculated value：C 57.75, H 4.85, N 6.12；Measured value：C 57.80, H
4.84, N 6.11.
FT-IR (KBr, ν/cm-1): 3566, 3022, 2918, 2860, 1637, 1618, 1597, 1525,
1492, 1386, 1338, 1317, 1226, 1170, 1134, 1105, 1014, 894, 858, 815, 758,
711, 588, 561, 505, 459, 418。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.30 (d, J =8.8 Hz, 2H), 8.09 (d, J =
8.8 Hz, 2H), 7.38 (d, J =7.7 Hz, 2H), 7.33 (t, J =7.7 Hz, 2H), 7.28 (d, J =
7.2 Hz, 1H), 6.67 (d, J =7.9 Hz, 4H), 6.62(d, J =7.9 Hz, 4H), 3.91 (s, 2H),
3.18 (d, J =11.7 Hz, 2H), 3.12 (d, J =11.7 Hz, 2H), 2.08 (s, 6H)。
13C NMR (126 MHz, CDCl3, δ/ppm): 172.94, 168.64, 153.45, 149.85,
139.11, 134.94, 134.80, 132.94, 129.91, 129.66, 128.88, 128.56, 128.12,
126.99, 123.20, 50.86, 36.66, 32.39, 20.87。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -636.93。
Crystallographic data：Monoclinic system, space group P2 (1)/n, a=1.6255 (2) nm, b=1.20419 (17) nm,
C=1.7800 (2) nm, α=γ=90 °, β=112.560 (4) °, Z=4, V=3.2175 (8) nm3, Dc=1.417
Mg·m-3, m (MoK α)=0.841 mm-1, F (000)=1400.
Test example：
2- carbonyl -3- phenylpropionic acid p-nitrophenyls the formyl hydrazone two of the present invention is external anti-to methylbenzyl tin complex
Cancer determination of activity is realized by MTT experiment method.
MTT analytic approach：
3- (4,5-Dimethylthiazol-2-yl) -2,5-diphenyltetrazolium is restored with metabolism
Based on bromide.Succinate dehydrogenase in living cells mitochondria can make exogenous MTT be reduced to the bluish violet of water-insoluble
Crystallization first a ceremonial jade-ladle, used in libation (Formazan) is simultaneously deposited in cell, and dead cell is without this function.Dimethyl sulfoxide (DMSO) (DMSO) can dissolve cell
In first a ceremonial jade-ladle, used in libation, with microplate reader measure characteristic wavelength optical density, can reflect living cells quantity indirectly.
2- carbonyl -3- phenylpropionic acid p-nitrophenyls the formyl hydrazones two of the preparation of embodiment 1 are measured to methyl benzyl using mtt assay
Inhibitory activity of the base tin complex to human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7).
Cell strain and cultivating system：H460, HepG2 and MCF7 cell strain are derived from American tissue incubator (ATCC).With containing
RPMI 1640 (GIBICO companies) culture medium of 10% fetal calf serum, in 5% (volume fraction) CO2, 37 DEG C of saturated humidity incubators
Interior carry out in vitro culture.
Test process：Test liquid (1nM ~ 10 μM) is added separately to according to the concentration gradient of concentration in each hole, often
A concentration sets 6 parallel holes.Experiment is divided into drug study group (the test medicine for being separately added into various concentration), control group (only plus is trained
Nutrient solution and cell are not added with test medicine) and blank group (only plus cultivating medicine, be not added with cell and test medicine).Orifice plate after dosing is set
In 37 DEG C, 5%CO272h is cultivated in incubator.The activity of control drug is measured according to the method for test sample.Cultivating 72h
In orifice plate afterwards, add 40 μ L of MTT (being made into 4mg/mL with D-Hanks buffer solutions) per hole.After placing 4h at 37 DEG C, upper layer is removed
Clear liquid.Add 150 μ L DMSO per hole, vibrate 5min, makes Formazan crystallization dissolvings.Finally, using automatic microplate reader in 570nm
The optical density in each hole is detected at wavelength.
Data processing：Data processing uses 7.0 programs of Graph Pad Prism version, complex IC50Pass through journey
The nonlinear regression model (NLRM) with S-shaped dose response is fitted to obtain in sequence.
It is thin to human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) with MTT analytic approach
Born of the same parents' strain is analyzed, its IC is measured50Value, the results are shown in Table 1, and conclusion is：From the data in the table, with the 2- carbonyls of the present invention
Base -3- phenylpropionic acid p-nitrophenyls formyl hydrazone two is used as anticancer drug to methylbenzyl tin complex, to human lung carcinoma cell
(H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7) have certain drug effect, can be used as the time of anticancer drug
Select compound.
1 2- carbonyl -3- phenylpropionic acid p-nitrophenyls formyl hydrazone two of table lives in vitro to methylbenzyl tin complex anticancer drug
Property test data.
| Human lung cancer | Human liver cancer | Human breast carcinoma | |
| Cell strain | H460 | HepG2 | MCF7 |
| IC50(μM) | 7.29±1.36 | 4.64±1.62 | 5.00±1.47 |
Remaining embodiment prepare 2- carbonyl -3- phenylpropionic acid p-nitrophenyls formyl hydrazone two to methylbenzyl tin complex with
Active anticancer test side of the mtt assay to human lung carcinoma cell (H460), human liver cancer cell (HepG2) and human breast cancer cell (MCF7)
The same test example of method, test result and table 1 are essentially identical.
It these are only the preferred embodiment of the present invention and test example, be not intended to restrict the invention, it is clear that the skill of this field
Art personnel can carry out the present invention various changes, modification without departing from the spirit and scope of the present invention.If to the present invention's
These modifications and variations within the scope of the claims of the present invention and its equivalent technology, belong to the protection model of the present invention
It encloses.
Claims (6)
1. a kind of two pairs of methylbenzyl tin complexs are the complex of following structure formula (I)：
(I)
Wherein Ph is phenyl, and R is to methylbenzyl；The complex (I) is crystal structure, and crystallographic data is as follows：It is single
Oblique system, space group P2 (1)/n, a=1.6255 (2) nm, b=1.20419 (17) nm, c=1.7800 (2) nm, α=
γ=90 °, β=112.560 (4) °, Z=4, V=3.2175 (8) nm3, the Mgm of Dc=1.417-3, m (MoK α)=0.841
mm-1, F (000)=1400；Tin atom is seven coordination distortion pentagonal bipyramid configurations in molecule；The complex (I) it is infrared
Spectroscopic data：FT-IR (KBr, ν/cm-1): 3566, 3022, 2918, 2860, 1637, 1618, 1597, 1525,
1492, 1386, 1338, 1317, 1226, 1170, 1134, 1105, 1014, 894, 858, 815, 758,
711, 588, 561, 505, 459, 418；Its nuclear-magnetism modal data：1H NMR (500 MHz, CDCl3, δ/ppm): 8.30
(d, J =8.8 Hz, 2H), 8.09 (d, J =8.8 Hz, 2H), 7.38 (d, J =7.7 Hz, 2H), 7.33
(t, J =7.7 Hz, 2H), 7.28 (d, J =7.2 Hz, 1H), 6.67 (d, J =7.9 Hz, 4H), 6.62(d,J =7.9 Hz, 4H), 3.91 (s, 2H), 3.18 (d, J =11.7 Hz, 2H), 3.12 (d, J =11.7 Hz,
2H), 2.08 (s, 6H)；13C NMR (126 MHz, CDCl3, δ/ppm): 172.94, 168.64, 153.45,
149.85, 139.11, 134.94, 134.80, 132.94, 129.91, 129.66, 128.88, 128.56,
128.12, 126.99, 123.20, 50.86, 36.66, 32.39, 20.87；119Sn NMR (187 MHz, CDCl3,
δ/ppm): -636.93；The complex (I) can be stabilized at 86 DEG C or less.
2. the preparation method of two pairs of methylbenzyls tin complex described in claim 1, it is characterized in that there is the anti-of nitrogen protection
It answers and two pairs of methylbenzyl stannous chloride, p-nitrobenzoylhydrazide, Sodium.beta.-phenylpyruvate and solvent absolute methanol is added in container, in temperature
Degree reacts 5 ~ 20 h under conditions of being 50 ~ 65 DEG C, cooling, filtering controls solvent volatilization crystallization under conditions of 20 ~ 35 DEG C, obtains
Yellow transparent crystal, as two pairs of methylbenzyl tin complexs.
3. preparation method as claimed in claim 2, which is characterized in that two pairs of methylbenzyl stannous chloride, p-nitrophenyls
Formylhydrazine, Sodium.beta.-phenylpyruvate three substance amount ratio be 1:(1~1.05):(1.05~1.15).
4. preparation method as claimed in claim 2, which is characterized in that the solvent absolute methanol dosage is two pairs every mM
Methylbenzyl stannous chloride adds 15 ~ 35 milliliters.
5. application of two pairs of methylbenzyl tin complexs in preparing anticancer drug described in claim 1.
6. the application described in claim 5, wherein the cancer cell is human lung carcinoma cell, human liver cancer cell, human breast cancer cell.
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