CN109438505A - A kind of α-furyl formyl hydrazone double-core organotin complex - Google Patents
A kind of α-furyl formyl hydrazone double-core organotin complex Download PDFInfo
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- 238000002360 preparation method Methods 0.000 claims abstract description 16
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 13
- 229940041181 antineoplastic drug Drugs 0.000 claims abstract description 13
- 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 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 27
- 239000013078 crystal Substances 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 10
- 206010009944 Colon cancer Diseases 0.000 claims description 9
- 201000007270 liver cancer Diseases 0.000 claims description 9
- 208000014018 liver neoplasm Diseases 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- VTESCYNPUGSWKG-UHFFFAOYSA-N (4-tert-butylphenyl)hydrazine;hydrochloride Chemical compound [Cl-].CC(C)(C)C1=CC=C(N[NH3+])C=C1 VTESCYNPUGSWKG-UHFFFAOYSA-N 0.000 claims description 8
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 8
- 208000029742 colonic neoplasm Diseases 0.000 claims description 8
- 238000000902 119Sn nuclear magnetic resonance spectroscopy Methods 0.000 claims description 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 claims description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 claims description 7
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 238000002447 crystallographic data Methods 0.000 claims description 6
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical group [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 5
- 208000019065 cervical carcinoma Diseases 0.000 claims description 5
- 229910052718 tin Inorganic materials 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 238000005580 one pot reaction Methods 0.000 claims description 4
- 201000005296 lung carcinoma Diseases 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 210000004251 human milk Anatomy 0.000 claims description 2
- 235000020256 human milk Nutrition 0.000 claims description 2
- 208000009956 adenocarcinoma Diseases 0.000 claims 1
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 claims 1
- 230000005311 nuclear magnetism Effects 0.000 claims 1
- XOLBLPGZBRYERU-UHFFFAOYSA-N tin dioxide Chemical compound O=[Sn]=O XOLBLPGZBRYERU-UHFFFAOYSA-N 0.000 claims 1
- 229910001887 tin oxide Inorganic materials 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 38
- 239000003814 drug Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 8
- 206010006187 Breast cancer Diseases 0.000 description 7
- 208000026310 Breast neoplasm Diseases 0.000 description 7
- 238000000921 elemental analysis Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 230000001093 anti-cancer Effects 0.000 description 5
- 201000005202 lung cancer Diseases 0.000 description 5
- 208000020816 lung neoplasm Diseases 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- XZBIXDPGRMLSTC-UHFFFAOYSA-N formohydrazide Chemical compound NNC=O XZBIXDPGRMLSTC-UHFFFAOYSA-N 0.000 description 4
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- -1 benzoyl benzoyl Chemical group 0.000 description 3
- 201000010881 cervical cancer Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 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 3
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000007547 defect Effects 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
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 2
- 150000007857 hydrazones Chemical class 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000005259 measurement Methods 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
- 238000012545 processing Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 238000004566 IR 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
- 239000002253 acid Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- DALDUXIBIKGWTK-UHFFFAOYSA-N benzene;toluene Chemical class C1=CC=CC=C1.CC1=CC=CC=C1 DALDUXIBIKGWTK-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000007787 solid 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
- 238000010189 synthetic method Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 238000001942 tin-119 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Classifications
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a kind of α-furyl formyl hydrazone double-core organotin complexes, are the complex of following structure formula (I), wherein R is normal-butyl, and Ph is phenyl.The invention also discloses the preparation method of the α-furyl formyl hydrazone double-core organotin complex and preparing the application in anticancer drug.
Description
Technical field
The present invention relates to a kind of α-furyl formyl hydrazone double-core organotin complex and preparation method thereof and the α-furyl first
Acylhydrazone double-core organotin complex is preparing the application in anticancer drug.
Background technique
Acylhydrazone is condensed by aldehydes or ketones and hydrazides, has good bioactivity, stronger configurational energy
Power and multiplicity coordination mode, and medicine, pesticide, material and in terms of have a wide range of applications.In recent years,
Domestic and international many researchers compare it in terms of bioactivity in depth to be studied, and discovery acylhydrazone has
The various actives such as anticancer, sterilization, anti-inflammatory.Organotin is the metallo-organic compound containing Sn-C key, and it is extensive studies have shown that
Many organotin complexes have excellent anti-tumor activity.By acylhydrazone ligand in conjunction with organotin, it is expected to obtain selectivity more
By force, the better anti-tumor drug of effect.
Patent CN 102718794A discloses a kind of double acylhydrazone class Schiff stannous phenide complexs and its anti-in preparation
Adenocarcinoma of lung, colon cancer, leukaemia cell drug in application.
Patent CN 101851251A discloses a kind of dibutyl tin complex of acylhydrazone class Schiff ligand and its is making
Standby treatment liver cancer, adenocarcinoma of lung, breast cancer, prostate cancer, colon cancer or the early application in the drug of young grain leukaemia.
Series of patents CN105777799A, CN106220675A, CN106279250A, CN106279260A,
CN106317105A、CN106366118A、CN106380480A、CN105693763A、CN106220668A、
CN106220670A、CN106220676A、CN106220678A、CN106279252A、CN106279258A、
CN106279261A、CN106336429A、CN105732697A、CN106220669A、CN106220672A、
CN106220674A、CN106220677A、CN106366119A、CN105384770A、CN105541898A、
CN105601663A、CN105601664A、CN105237563A、CN105237564A、CN105399765A、CN105399764A
It discloses the organotin complex of serial substituted benzoyl benzoyl hydrazone and preparation method and is preparing the application in anticancer drug,
Described in the cancer cell applied be human colon cancer cell (Colo205) or human liver cancer cell (HepG2) or breast cancer cell
(MCF7) or cervical cancer cell (Hela) or human lung carcinoma cell (NCI-H460).
Document (Solid State Sciences, 2011,13 (03): 501-507) reports serial substituted benzene toluene
The organotin complex of formyl hydrazone or thenoyl hydrazone.
Document (Inorganica Chimica Acta, 2007,360 (07): 2215-2223) reports serial thiophene
The organotin complex of formyl hydrazone.
Method used by the synthesis of above-mentioned acylhydrazone organotin complex has multistep processes synthesis and one pot process, wherein more
Footwork synthesis step is long, and the reaction time is long, at high cost, low efficiency；Though one pot process reduces synthesis step, there are still
The problem of reaction time is long, and energy consumption is high, low efficiency.To solve the defects of above-mentioned document synthesis, the present invention devises microwave one
The synthetic method of pot method, overcomes the defect of multistep processes and common one kettle way, and synthesis has been obtained to people's colon under certain condition
Cancer cell (Colo205), human liver cancer cell (HepG2), breast cancer cell (MCF7), cervical cancer cell (Hela) and human lung cancer
Cell (NCI-H460) has the acylhydrazone organotin complex of certain inhibitory activity, provides new way for exploitation anticancer drug
Diameter.
Summary of the invention
There is provided a kind of α-furyl formyl hydrazone double-core organotin complexes for the first object of the present invention.
The second object of the present invention is to provide above-mentioned α-furyl formyl hydrazone double-core organotin complex preparation method.
The third object of the present invention is to provide above-mentioned α-furyl formyl hydrazone double-core organotin complex and is preparing anticancer drug
In application.
A kind of α-furyl formyl hydrazone double-core organotin complex as the first aspect of the present invention is structure formula (I)
Complex
(I)
Wherein R is normal-butyl, and Ph is phenyl.
α-furyl formyl hydrazone double-core organotin complex of the invention through elemental analysis, infrared spectroscopy, nuclear magnetic resoance spectrum and
X-ray single crystal diffraction structural analysis, as a result as follows:
Elemental analysis (C22H30N2O5Sn): calculated value: C 50.70, H 5.80, N 5.37；Measured value: C 50.63, H 5.76, N
5.35。
FT-IR (KBr, ν/cm-1): 3136, 2958, 2922, 2854, 1627, 1597, 1500, 1475,
1462, 1402, 1315, 1300, 1251, 1195, 1138, 1085, 1024, 1008, 887, 756, 688,
630, 596, 516, 474, 418。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.12-8.14 (m, 2H), 7.62 (s, 1H), 7.52-
7.53 (m, 3H), 7.23 (d, J = 3.5 Hz, 1H), 6.54-6.55 (m, 1H), 1.70-1.76(m, 4H),
1.60-1.66(m, 4H), 1.32-1.39 (m, 4H), 0.88 (t, J = 7.3 Hz, 6H)。
13C NMR (125 MHz, CDCl3, δ/ppm): 168.03, 164.17, 149.79, 147.48,
146.28, 132.08, 131.50, 128.82, 127.70, 117.06, 112.22, 50.78, 26.77, 26.44,
22.68, 13.47。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -181.64。
α-furyl formyl hydrazone double-core organotin complex of the invention is crystal structure, and crystal is anorthic system, space
Group P, a=1.04219 (11) nm, b=1.19101 (13) nm, c=1.22031 (13) nm, α=91.2640 (10) °,
β=114.5810 (10) °, γ=115.7810 (10) °, Z=2, V=1.2016 (2) nm3, the Mgm of Dc=1.440-3, m
(MoKα)= 1.096 mm-1, F (000)=532.
α-furyl formyl hydrazone double-core organotin complex of the invention is structurally characterized in that: tin atom is seven coordinations in molecule
Distort pentagonal bipyramid configuration.
α-furyl formyl hydrazone double-core organotin complex of the invention, which is characterized in that there is certain thermostabilization range,
It can be stabilized at 81 DEG C or less.
A kind of preparation method of α-furyl formyl hydrazone double-core organotin complex as a second aspect of the invention, it is special
Sign is that di-nbutyltin oxide, α-furyl formylhydrazine, benzoyl first are added in microwave reaction tank using microwave one pot process
Acid and solvent anhydrous methanol, react 10 ~ 100 min under conditions of temperature is 60 ~ 120 DEG C, and program is cooled to 25 DEG C, obtains yellow
Transparent crystal, as furoyl hydrazone double-core dibutyl tin complex.
In a preferred embodiment of the invention, the di-nbutyltin oxide, α-furyl formylhydrazine, benzoyl formic acid
The mass ratio of the material of three is 1:(1 ~ 1.05): (1 ~ 1.1).
In a preferred embodiment of the invention, the solvent anhydrous methanol dosage is every mM of di-n-butyl oxidation
Tin adds 5 ~ 35 milliliters.
In a preferred embodiment of the invention, described program cooling conditions are 0.1 ~ 20 DEG C/h.
A kind of α-furyl formyl hydrazone double-core organotin complex as the third aspect of the present invention is preparing anticancer drug
In application.
Applicant has carried out anti tumor activity in vitro to above-mentioned α-furyl formyl hydrazone double-core organotin complex and has determined research,
It confirmed that α-furyl formyl hydrazone double-core organotin complex has certain anticancer bioactive, that is to say, that above-mentioned complex
Purposes is to prepare the application in anticancer drug, is specifically exactly to prepare anti-human colon cancer, human liver cancer, human breast carcinoma, people
Application in cervix cancer, human lung cancer drug.
α-furyl formyl hydrazone double-core organotin complex of the invention is to human colon cancer cell, human liver cancer cell, human milk gland
Cancer cell, human cervical carcinoma cell, human lung carcinoma cell etc. show good anticancer activity, and α-furyl formyl hydrazone of the invention is double
The features such as core organotin complex anticancer activity is high, at low cost, preparation method is simple, the anticancer drug to develop new provide newly
Approach.
Detailed description of the invention
Fig. 1 is the crystal structure figure of α-furyl formyl hydrazone double-core organotin complex.
Fig. 2 is the IR spectrogram of α-furyl formyl hydrazone double-core organotin complex.
Fig. 3 is α-furyl formyl hydrazone double-core organotin complex1H NMR spectra.
Fig. 4 is α-furyl formyl hydrazone double-core organotin complex13C NMR spectra.
Fig. 5 is α-furyl formyl hydrazone double-core organotin complex119Sn NMR spectra.
Fig. 6 is the TG-DTG curve of α-furyl formyl hydrazone double-core organotin complex.
Specific embodiment
By following embodiment, present invention be described in more detail, but should be noted that the scope of the present invention is not implemented by these
Any restrictions of example.
Embodiment 1:
The preparation of α-furyl formyl hydrazone double-core organotin complex:
0.248g (1.0mmol) di-nbutyltin oxide, 0.126g (1.0mmol) α-furyl first are added in microwave reaction tank
Hydrazides, 0.150g (1.0mmol) benzoyl formic acid and 20mL solvent anhydrous methanol react 60 under conditions of temperature is 100 DEG C
Min is arranged the program cooling conditions of 13 DEG C/h, is down to 25 DEG C, obtains yellow transparent crystal, as α-furyl formyl hydrazone double-core is organic
Tin complex.Yield: 82.4%.Fusing point: 81 ~ 82 DEG C (dec).
Elemental analysis (C22H30N2O5Sn): calculated value: C 50.70, H 5.80, N 5.37；Measured value: C 50.63, H
5.76, N 5.35.
FT-IR (KBr, ν/cm-1): 3136, 2958, 2922, 2854, 1627, 1597, 1500, 1475,
1462, 1402, 1315, 1300, 1251, 1195, 1138, 1085, 1024, 1008, 887, 756, 688,
630, 596, 516, 474, 418。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.12-8.14 (m, 2H), 7.62 (s, 1H), 7.52-
7.53 (m, 3H), 7.23 (d, J = 3.5 Hz, 1H), 6.54-6.55 (m, 1H), 1.70-1.76(m, 4H),
1.60-1.66(m, 4H), 1.32-1.39 (m, 4H), 0.88 (t, J = 7.3 Hz, 6H)。
13C NMR (125 MHz, CDCl3, δ/ppm): 168.03, 164.17, 149.79, 147.48,
146.28, 132.08, 131.50, 128.82, 127.70, 117.06, 112.22, 50.78, 26.77, 26.44,
22.68, 13.47。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -181.64。
Crystallographic data: anorthic system, space group P, a=1.04219 (11) nm, b=1.19101 (13) nm, c=
1.22031 (13) nm, α=91.2640 (10) °, β=114.5810 (10) °, γ=115.7810 (10) °, Z=2, V=
1.2016(2) nm3, the Mgm of Dc=1.440-3, m (MoK α)=1.096 mm-1, F (000)=532.
Embodiment 2:
The preparation of α-furyl formyl hydrazone double-core organotin complex:
0.248g (1.0mmol) di-nbutyltin oxide, 0.128g (1.02mmol) α-furyl are added in microwave reaction tank
Formylhydrazine, 0.153g (1.02mmol) benzoyl formic acid and 30mL solvent anhydrous methanol react under conditions of temperature is 80 DEG C
40 min are arranged the program cooling conditions of 5 DEG C/h, are down to 25 DEG C, obtain yellow transparent crystal, as α-furyl formyl hydrazone double-core has
Machine tin complex.Yield: 87.4%.Fusing point: 81 ~ 82 DEG C (dec).
Elemental analysis (C22H30N2O5Sn): calculated value: C 50.70, H 5.80, N 5.37；Measured value: C 50.63, H
5.76, N 5.35.
FT-IR (KBr, ν/cm-1): 3136, 2958, 2922, 2854, 1627, 1597, 1500, 1475,
1462, 1402, 1315, 1300, 1251, 1195, 1138, 1085, 1024, 1008, 887, 756, 688,
630, 596, 516, 474, 418。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.12-8.14 (m, 2H), 7.62 (s, 1H), 7.52-
7.53 (m, 3H), 7.23 (d, J = 3.5 Hz, 1H), 6.54-6.55 (m, 1H), 1.70-1.76(m, 4H),
1.60-1.66(m, 4H), 1.32-1.39 (m, 4H), 0.88 (t, J = 7.3 Hz, 6H)。
13C NMR (125 MHz, CDCl3, δ/ppm): 168.03, 164.17, 149.79, 147.48,
146.28, 132.08, 131.50, 128.82, 127.70, 117.06, 112.22, 50.78, 26.77, 26.44,
22.68, 13.47。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -181.64。
Crystallographic data: anorthic system, space group P, a=1.04219 (11) nm, b=1.19101 (13) nm, c=
1.22031 (13) nm, α=91.2640 (10) °, β=114.5810 (10) °, γ=115.7810 (10) °, Z=2, V=
1.2016(2) nm3, the Mgm of Dc=1.440-3, m (MoK α)=1.096 mm-1, F (000)=532.
Embodiment 3:
The preparation of α-furyl formyl hydrazone double-core organotin complex:
0.248g (1.0mmol) di-nbutyltin oxide, 0.132g (1.05mmol) α-furyl are added in microwave reaction tank
Formylhydrazine, 0.162g (1.08mmol) benzoyl formic acid and 10mL solvent anhydrous methanol, react under the conditions of at a temperature of 90 °C
90 min are arranged the program cooling conditions of 14 DEG C/h, are down to 25 DEG C, obtain yellow transparent crystal, as α-furyl formyl hydrazone double-core
Organotin complex.Yield: 88.4%.Fusing point: 81 ~ 82 DEG C (dec).
Elemental analysis (C22H30N2O5Sn): calculated value: C 50.70, H 5.80, N 5.37；Measured value: C 50.63, H
5.76, N 5.35.
FT-IR (KBr, ν/cm-1): 3136, 2958, 2922, 2854, 1627, 1597, 1500, 1475,
1462, 1402, 1315, 1300, 1251, 1195, 1138, 1085, 1024, 1008, 887, 756, 688,
630, 596, 516, 474, 418。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.12-8.14 (m, 2H), 7.62 (s, 1H), 7.52-
7.53 (m, 3H), 7.23 (d, J = 3.5 Hz, 1H), 6.54-6.55 (m, 1H), 1.70-1.76(m, 4H),
1.60-1.66(m, 4H), 1.32-1.39 (m, 4H), 0.88 (t, J = 7.3 Hz, 6H)。
13C NMR (125 MHz, CDCl3, δ/ppm): 168.03, 164.17, 149.79, 147.48,
146.28, 132.08, 131.50, 128.82, 127.70, 117.06, 112.22, 50.78, 26.77, 26.44,
22.68, 13.47。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -181.64。
Crystallographic data: anorthic system, space group P, a=1.04219 (11) nm, b=1.19101 (13) nm, c=
1.22031 (13) nm, α=91.2640 (10) °, β=114.5810 (10) °, γ=115.7810 (10) °, Z=2, V=
1.2016(2) nm3, the Mgm of Dc=1.440-3, m (MoK α)=1.096 mm-1, F (000)=532.
Embodiment 4:
The preparation of α-furyl formyl hydrazone double-core organotin complex:
0.248g (1.0mmol) di-nbutyltin oxide, 0.132g (1.05mmol) α-furyl are added in microwave reaction tank
Formylhydrazine, 0.165g (1.10mmol) benzoyl formic acid and 10mL solvent anhydrous methanol, it is anti-under conditions of temperature is 120 DEG C
10 min are answered, the program cooling conditions of 0.8 DEG C/h are set, are down to 25 DEG C, obtain yellow transparent crystal, as α-furyl formyl hydrazone is double
Core organotin complex.Yield: 89.8%.Fusing point: 81 ~ 82 DEG C (dec).
Elemental analysis (C22H30N2O5Sn): calculated value: C 50.70, H 5.80, N 5.37；Measured value: C 50.63, H
5.76, N 5.35.
FT-IR (KBr, ν/cm-1): 3136, 2958, 2922, 2854, 1627, 1597, 1500, 1475,
1462, 1402, 1315, 1300, 1251, 1195, 1138, 1085, 1024, 1008, 887, 756, 688,
630, 596, 516, 474, 418。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.12-8.14 (m, 2H), 7.62 (s, 1H), 7.52-
7.53 (m, 3H), 7.23 (d, J = 3.5 Hz, 1H), 6.54-6.55 (m, 1H), 1.70-1.76(m, 4H),
1.60-1.66(m, 4H), 1.32-1.39 (m, 4H), 0.88 (t, J = 7.3 Hz, 6H)。
13C NMR (125 MHz, CDCl3, δ/ppm): 168.03, 164.17, 149.79, 147.48,
146.28, 132.08, 131.50, 128.82, 127.70, 117.06, 112.22, 50.78, 26.77, 26.44,
22.68, 13.47。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -181.64。
Crystallographic data: anorthic system, space group P, a=1.04219 (11) nm, b=1.19101 (13) nm, c=
1.22031 (13) nm, α=91.2640 (10) °, β=114.5810 (10) °, γ=115.7810 (10) °, Z=2, V=
1.2016(2) nm3, the Mgm of Dc=1.440-3, m (MoK α)=1.096 mm-1, F (000)=532.
Embodiment 5:
The preparation of α-furyl formyl hydrazone double-core organotin complex:
0.496g (2.0mmol) di-nbutyltin oxide, 0.258g (2.05mmol) α-furyl are added in microwave reaction tank
Formylhydrazine, 0.315g (2.10mmol) benzoyl formic acid and 15mL solvent anhydrous methanol react under conditions of temperature is 60 DEG C
50 min are arranged the program cooling conditions of 20 DEG C/h, are down to 25 DEG C, obtain yellow transparent crystal, as α-furyl formyl hydrazone double-core
Organotin complex.Yield: 85.8%.Fusing point: 81 ~ 82 DEG C (dec).
Elemental analysis (C22H30N2O5Sn): calculated value: C 50.70, H 5.80, N 5.37；Measured value: C 50.63, H
5.76, N 5.35.
FT-IR (KBr, ν/cm-1): 3136, 2958, 2922, 2854, 1627, 1597, 1500, 1475,
1462, 1402, 1315, 1300, 1251, 1195, 1138, 1085, 1024, 1008, 887, 756, 688,
630, 596, 516, 474, 418。
1H NMR (500 MHz, CDCl3, δ/ppm): 8.12-8.14 (m, 2H), 7.62 (s, 1H), 7.52-
7.53 (m, 3H), 7.23 (d, J = 3.5 Hz, 1H), 6.54-6.55 (m, 1H), 1.70-1.76(m, 4H),
1.60-1.66(m, 4H), 1.32-1.39 (m, 4H), 0.88 (t, J = 7.3 Hz, 6H)。
13C NMR (125 MHz, CDCl3, δ/ppm): 168.03, 164.17, 149.79, 147.48,
146.28, 132.08, 131.50, 128.82, 127.70, 117.06, 112.22, 50.78, 26.77, 26.44,
22.68, 13.47。
119Sn NMR (187 MHz, CDCl3, δ/ppm): -181.64。
Crystallographic data: anorthic system, space group P, a=1.04219 (11) nm, b=1.19101 (13) nm, c=
1.22031 (13) nm, α=91.2640 (10) °, β=114.5810 (10) °, γ=115.7810 (10) °, Z=2, V=
1.2016(2) nm3, the Mgm of Dc=1.440-3, m (MoK α)=1.096 mm-1, F (000)=532.
Test example:
α-furyl formyl hydrazone double-core organotin complex of the invention, Anticancer Activity in vitro measurement is by MTT experiment method
It realizes.
MTT analytic approach:
It is with metabolism reduction 3- (4,5-Dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide
Basis.The bluish violet that succinate dehydrogenase in living cells mitochondria can make exogenous MTT be reduced to water-insoluble crystallizes first a ceremonial jade-ladle, used in libation
(Formazan) it and is deposited in cell, and dead cell is without this function.Dimethyl sulfoxide (DMSO) can dissolve the first a ceremonial jade-ladle, used in libation in cell,
With the optical density of microplate reader measurement characteristic wavelength, it can reflect living cells quantity indirectly.
The α-furyl formyl hydrazone double-core organotin complex that the preparation of embodiment 1 is measured using mtt assay is thin to human colon carcinoma
Born of the same parents (Colo205), human liver cancer cell (HepG2), human breast cancer cell (MCF7), human cervical carcinoma cell (Hela) and human lung cancer
The inhibitory activity of cell (NCI-H460).
Cell strain and cultivating system: Colo205, HepG2, MCF7, Hela and NCI-H460 cell strain are derived from American tissue
Incubator (ATCC).With the RPMI 1640(GIBICO company for containing 10% fetal calf serum) culture medium, in 5%(volume fraction) CO2、
In vitro culture is carried out in 37 DEG C of saturated humidity incubators.
Test process: test medical fluid (0.1nM ~ 10uM) is added separately in each hole according to the concentration gradient of concentration,
Each 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 adds
Test medicine is not added in culture solution and cell) and blank group (only plus cultivating medicine, cell and test medicine is not added).By the orifice plate after dosing
37 DEG C are placed in, 5%CO272h is cultivated in incubator.The activity of control drug is measured according to the method for test sample.It is cultivating
In orifice plate after 72h, every hole adds MTT 40uL(to be made into 4mg/mL with D-Hanks buffer).After 37 DEG C of placement 4h, remove
Layer clear liquid.Every hole adds 150uL DMSO, vibrates 5min, makes Formazan crystallization dissolution.Finally, being existed using automatic microplate reader
The optical density in each hole is detected at 570nm wavelength.
Data processing: data processing uses 7.0 program of Graph Pad Prism version, complex IC50Pass through journey
Nonlinear regression model (NLRM) in sequence with S-shaped dose response is fitted to obtain.
The α-furyl formyl hydrazone double-core organotin complex of each embodiment preparation is with MTT analytic approach to human colon cancer cell
(Colo205), human liver cancer cell (HepG2), human breast cancer cell (MCF7), human cervical carcinoma cell (Hela) and human lung cancer are thin
Born of the same parents (NCI-H460) cell strain is analyzed, its IC is measured50Value, average result is as shown in table 1, conclusion are as follows: can by data in table
Know, anticancer drug is used as with α-furyl formyl hydrazone double-core organotin complex of the invention, to human colon cancer cell
(Colo205), human liver cancer cell (HepG2), human breast cancer cell (MCF7), human cervical carcinoma cell (Hela) and human lung cancer are thin
Born of the same parents (NCI-H460) have certain drug effect, can be used as the candidate compound of anticancer drug.
1 α-furyl formyl hydrazone double-core organotin complex anticancer drug external activity test data of table.
Claims (10)
1. a kind of α-furyl formyl hydrazone double-core organotin complex is the complex of following structure formula (I):
(I)
Wherein R is normal-butyl, and Ph is phenyl.
2. containing a kind of α-furyl formyl hydrazone double-core organotin complex as described in claim 1, ir data:
FT-IR (KBr, ν/cm-1): 3136, 2958, 2922, 2854, 1627, 1597, 1500, 1475, 1462,
1402, 1315, 1300, 1251, 1195, 1138, 1085, 1024, 1008, 887, 756, 688, 630,
596, 516, 474, 418；Its nuclear-magnetism modal data:1H NMR (500 MHz, CDCl3, δ/ppm): 8.12-8.14 (m,
2H), 7.62 (s, 1H), 7.52-7.53 (m, 3H), 7.23 (d, J = 3.5 Hz, 1H), 6.54-6.55 (m,
1H), 1.70-1.76(m, 4H), 1.60-1.66(m, 4H), 1.32-1.39 (m, 4H), 0.88 (t, J = 7.3
Hz, 6H)；13C NMR (125 MHz, CDCl3, δ/ppm): 168.03, 164.17, 149.79, 147.48,
146.28, 132.08, 131.50, 128.82, 127.70, 117.06, 112.22, 50.78, 26.77, 26.44,
22.68, 13.47；119Sn NMR (187 MHz, CDCl3, δ/ppm): -181.64。
3. α-furyl formyl hydrazone double-core organotin complex as described in claim 1, wherein the α-furyl formyl hydrazone
Double-core organotin complex is crystal structure, and crystallographic data is as follows: anorthic system, space group P, a=1.04219 (11)
Nm, b=1.19101 (13) nm, c=1.22031 (13) nm, α=91.2640 (10) °, β=114.5810 (10) °, γ
=115.7810 (10) °, Z=2, V=1.2016 (2) nm3, the Mgm of Dc=1.440-3, m (MoK α)=1.096 mm-1, F
(000) = 532；Tin atom is seven coordination distortion pentagonal bipyramid configurations in molecule.
4. α-furyl formyl hydrazone double-core organotin complex described in claim 1, which is characterized in that have certain thermostabilization model
It encloses, can be stabilized at 81 DEG C or less.
5. the preparation method of α-furyl formyl hydrazone double-core organotin complex described in claim 1, it is characterized in that using microwave
It is anhydrous that di-nbutyltin oxide, α-furyl formylhydrazine, benzoyl formic acid and solvent is added in one pot process in microwave reaction tank
Methanol, reacts 10 ~ 100 min under conditions of temperature is 60 ~ 120 DEG C, and program is cooled to 25 DEG C, obtains yellow transparent crystal, i.e.,
For α-furyl formyl hydrazone double-core organotin complex.
6. the method prepared as claimed in claim 5, which is characterized in that the di-nbutyltin oxide, α-furyl formylhydrazine,
The mass ratio of the material of benzoyl formic acid three is 1:(1 ~ 1.05): (1 ~ 1.1).
7. the method prepared as claimed in claim 5, which is characterized in that the solvent anhydrous methanol dosage is the positive fourth of every milli two
Base tin oxide adds 5 ~ 35 milliliters.
8. preparation method as claimed in claim 5, which is characterized in that described program cooling conditions are 0.1 ~ 20 DEG C/h.
9. α-furyl formyl hydrazone double-core organotin complex described in claim 1 is preparing the application in anticancer drug.
10. application as claimed in claim 9, wherein the cancer cell of the application is human colon cancer cell, human liver cancer cell, human milk
Adenocarcinoma cell, human cervical carcinoma cell, human lung carcinoma cell.
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| HONG MIN等: "Bis[μ-furan-2-carbaldehyde (1-carboxyethylidene)hydrazonato(2-)]bis[methanoldimethyltin(IV)]", 《ACTA CRYSTALLOGRAPHICA, SECTION E: STRUCTURE REPORTS ONLINE》 * |
| MIN HONG等: "Weakly-bridged dimeric diorganotin(IV) compounds derived from pyruvic acid hydrazone Schiff base ligands: Synthesis, characterization and crystal structures", 《SOLID STATE SCIENCES》 * |
| YIN HANDONG等: "Synthesis, characterization and crystal structures of the organotin(IV) compounds with the Schiff base ligands of pyruvic acid thiophene-2-carboxylic hydrazone and salicylaldehyde thiophene-2-carboxylic hydrazone", 《INORGANICA CHIMICA ACTA》 * |
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