CN105693761A - 2-carbonyl-3-phenylpropionic acid salicylacylhydrazone diphenyl tin complex as well as preparation method and application thereof - Google Patents
2-carbonyl-3-phenylpropionic acid salicylacylhydrazone diphenyl tin complex as well as preparation method and application thereof Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- NSZRQCQXHMPQEY-UHFFFAOYSA-N C(=O)=C(C(=O)O)CC1=CC=CC=C1 Chemical compound C(=O)=C(C(=O)O)CC1=CC=CC=C1 NSZRQCQXHMPQEY-UHFFFAOYSA-N 0.000 title abstract 3
- KUCPUSUXIGWHFB-UHFFFAOYSA-N diphenyltin Chemical compound C=1C=CC=CC=1[Sn]C1=CC=CC=C1 KUCPUSUXIGWHFB-UHFFFAOYSA-N 0.000 title abstract 3
- 238000010668 complexation reaction Methods 0.000 title 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 54
- XPHZFLYJHXEWEC-UHFFFAOYSA-N C(C=1C(O)=CC=CC=1)(=O)NN=C(C(CC1=CC=CC=C1)=C=O)O Chemical compound C(C=1C(O)=CC=CC=1)(=O)NN=C(C(CC1=CC=CC=C1)=C=O)O XPHZFLYJHXEWEC-UHFFFAOYSA-N 0.000 claims description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- 239000003814 drug Substances 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- -1 diphenyl stannum Chemical compound 0.000 claims description 14
- XSXYESVZDBAKKT-UHFFFAOYSA-N 2-hydroxybenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1O XSXYESVZDBAKKT-UHFFFAOYSA-N 0.000 claims description 13
- 235000010290 biphenyl Nutrition 0.000 claims description 13
- 239000004305 biphenyl Substances 0.000 claims description 13
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 13
- 206010009944 Colon cancer Diseases 0.000 claims description 12
- 208000029742 colonic neoplasm Diseases 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 12
- 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 11
- 238000002425 crystallisation Methods 0.000 claims description 10
- 230000008025 crystallization Effects 0.000 claims description 10
- 238000011275 oncology therapy Methods 0.000 claims description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 claims description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 claims description 9
- 206010006187 Breast cancer Diseases 0.000 claims description 9
- 208000026310 Breast neoplasm Diseases 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 claims description 8
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 8
- 239000013078 crystal Substances 0.000 claims description 8
- 201000007270 liver cancer Diseases 0.000 claims description 8
- 208000014018 liver neoplasm Diseases 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 208000019065 cervical carcinoma Diseases 0.000 claims description 7
- 201000005296 lung carcinoma Diseases 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 2
- 230000005311 nuclear magnetism Effects 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 abstract 1
- 229940041181 antineoplastic drug Drugs 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 47
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- 238000004364 calculation method Methods 0.000 description 7
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- 238000000338 in vitro Methods 0.000 description 6
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 201000005249 lung adenocarcinoma Diseases 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
- 239000002262 Schiff base Substances 0.000 description 2
- 150000004753 Schiff bases Chemical class 0.000 description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical group [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 201000008275 breast carcinoma Diseases 0.000 description 2
- 239000000463 material Substances 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
- 229910052718 tin Inorganic materials 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
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028980 Neoplasm 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
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 201000011510 cancer Diseases 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
- 150000007942 carboxylates Chemical class 0.000 description 1
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- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000012531 culture fluid Substances 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
- 230000000857 drug effect Effects 0.000 description 1
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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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a 2-carbonyl-3-phenylpropionic acid salicylacylhydrazone diphenyl tin complex which is a complex with a structural formula (I) shown in the specification, wherein Ph is phenyl. The invention also discloses a preparation method of the 2-carbonyl-3-phenylpropionic acid salicylacylhydrazone diphenyl tin complex and an application in preparing anti-cancer drugs.
Description
Technical field
The present invention relates to a kind of 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound and preparation method thereof and this 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound application in preparing cancer therapy drug。
Background technology
Organotin is the metallo-organic compound that a class contains Sn-C key。Researcher just noticed the Anticancer Activity in vitro of organo-tin compound before very early。1972, Brown found Ph first3SnOOCCH3The growth of mice cancerous cell is inhibited。1980, the research of the chemists such as Crowe showed, many organo-tin compounds have anti tumor activity in vitro。1989, more than 2,000 kinds of organo-tin compounds were carried out antitumor activity screening by American National anticancer research institute (NationalCancerInstitute), and result shows that P388 Lymphocytic leukemia is had inhibitory action by some organo-tin compounds。2002, Gielen et al., the activity of organotin carboxylate's ester compounds has been done comprehensive summing up, thought after research that many organo-tin compounds have good Anticancer Activity in vitro really。
Research shows, the organic group connected on organotin atom and the part participating in coordination decide the biological activity of organo-tin compound, select some itself to have the tin atom coordination in the organic ligand of good biological activity and organotin and cause the great interest of people。Acylhydrazone is the class Schiff compound modifiied by hydrazide kind compound, they are formed by aldehydes or ketones and hydrazides condensation, there is good biological activity, stronger coordination ability and various coordination mode, and have a wide range of applications in medicine, pesticide, material and analytical reagent etc.。In recent years, it is compared in biological activity and in depth studies by domestic and international many research worker, and research finds that acylhydrazone has the various active such as anticancer, sterilization, antiinflammatory。Therefore, acylhydrazone class Schiff part is combined with organotin, it is intended to obtain the noval chemical compound that biological activity is higher, becomes the research direction that people are interested。
Chinese patent CN102718794A discloses a kind of pair of acylhydrazone class Schiff stannous phenide coordination compound and the application in the medicine preparing Antilung gland cancer, colon cancer, leukaemia thereof。
Chinese patent CN101851251A discloses the dibutyl tin coordination compound of a kind of acylhydrazone class Schiff part and treats the application in hepatocarcinoma, adenocarcinoma of lung, breast carcinoma, carcinoma of prostate, colon cancer or the morning young leukemic medicine of grain in preparation。
Document (JournalofOrganometallicChemistry, 2014,75:83-91) report, human colon cancer cell (HCT-116), human lung adenocarcinoma cell (A549), Human umbilical vein endothelial cells (HUVEC) are had relatively strong biological activity, and are better than carboplatin by organotin acylhydrazone class Schiff base complex。
Document (JournalofOrganometallicChemistry, 2013,724:23-31) report, series organotin acylhydrazone class Schiff base complex, organo-tin compound and acylhydrazone class Schiff part inhibitory action to cancerous cell such as human lung adenocarcinoma cell (A549), human colon cancer cell (HCT-8), people in loop (hl-60) respectively。
Document (Bioorganic&MedicinalChemistryLetters, 2015,25:4461-4463) is reported, the multiple acylhydrazone class Schiff part active anticancer to human liver cancer cell (HuH-7) and human lung adenocarcinoma cell (A549)。
It is the material that the experiment proved that and there is active anticancer based on acylhydrazone class Schiff organotin complex, the present invention selects salicylyl hydrazine, Sodium.beta.-phenylpyruvate and diphenyl stannum dichloride to react under certain condition, it is synthetically derived the coordination compound that human colon cancer cell (Colo205), human liver cancer cell (HepG2), breast cancer cell (MCF7), cervical cancer cell (Hela) and human lung carcinoma cell (NCI-H460) are had certain inhibitory activity, provides new approach for exploitation cancer therapy drug。
Summary of the invention
The first object of the present invention there is provided a kind of 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound。
The second object of the present invention is to provide above-mentioned 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide complex preparation method。
The third object of the present invention is to provide the application in preparing cancer therapy drug of the above-mentioned 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound。
As a kind of 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound of a first aspect of the present invention, for the coordination compound of structural formula (I)
(I)
Wherein Ph is phenyl。
2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide the coordination compound of the present invention is through elementary analysis, infrared spectrum and nuclear magnetic resoance spectrum structural analysis, and result is as follows:
Elementary analysis (C28H22N2O4Sn): value of calculation: C59.08, H3.90, N4.92;Measured value: C59.14, H3.86, N4.89。
FT-IR(KBr,ν/cm-1):3423,3055,3030,1591,1512,1490,1454,1325,1192,731,694,596,567,455。
1HNMR(500MHz,CD3Cl)δ(ppm):11.44(s,1H),8.19-8.21(dd,J1=8.1Hz,J2=1.7Hz,1H),7.76(m,4H),7.40-7.52(m,9H),7.28-7.29(m,2H),7.20-7.23(m,1H),7.00-7.04(m,2H),4.34(s,2H),1.26(s,2H)。
13CNMR(125MHz,CD3Cl)δ(ppm):175.89,162.97,160.97,155.28,136.04,135.49,134.96,133.34,131.73,130.9,129.59,129.47,129.11,127.49,119.51,117.91,114.76,33.56。
Being structurally characterized in that of the 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound of the present invention: in molecule, tin atom is hexa-coordinate distorted octahedron configuration。
2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide the coordination compound of the present invention has certain thermally-stabilised scope, can stable existence below 254 DEG C。
Preparation method as a kind of 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound of a second aspect of the present invention; the reaction vessel have nitrogen protection adds diphenyl stannum dichloride, salicylyl hydrazine, Sodium.beta.-phenylpyruvate and solvent absolute methanol; 5 ~ 24h is reacted when temperature is 45 ~ 65 DEG C; cooling; filter; control solvent volatilization crystallization when 20 ~ 35 DEG C, obtain yellow transparent crystal, be 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound。
In a preferred embodiment of the invention, described diphenyl stannum dichloride, salicylyl hydrazine, Sodium.beta.-phenylpyruvate three amount of substance than for 1:(1 ~ 1.05): (1.05 ~ 1.15)。
In a preferred embodiment of the invention, described solvent absolute methanol consumption be every mM of diphenyl stannum dichloride add 15 ~ 35 milliliters。
As the application in preparing cancer therapy drug of a kind of 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound of a third aspect of the present invention。
Above-mentioned 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound has been carried out anti tumor activity in vitro and has determined research by applicant, confirm 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound and there is certain anticancer bioactive, that is the purposes of above-mentioned coordination compound is the application in preparing cancer therapy drug, is exactly the application in preparing anti-human colon cancer, people's hepatocarcinoma, human breast carcinoma, human cervical carcinoma, people's lung-cancer medicament specifically。
Human colon cancer cell, human liver cancer cell, human breast cancer cell, human cervical carcinoma cell, human lung carcinoma cell etc. are demonstrated good active anticancer by the 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound of the present invention, the features such as the 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound active anticancer of the present invention is high, cost is low, preparation method is simple, provide new way for developing new cancer therapy drug。
Accompanying drawing explanation
Fig. 1 is the IR spectrogram of 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound。
Fig. 2 is 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound1HNMR spectrogram。
Fig. 3 is 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound13CNMR spectrogram。
Fig. 4 is the TG-DTG curve of 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound。
Detailed description of the invention
Further describe the present invention by following example, but it should be noted that the scope of the present invention is not by any restriction of these embodiments。
Embodiment 1:
The preparation of 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound:
The 100mL there-necked flask have nitrogen protection adds 0.344g (1.0mmol) diphenyl stannum dichloride, 0.152g (1.0mmol) salicylyl hydrazine, 0.205g (1.1mmol) Sodium.beta.-phenylpyruvate and 25mL solvent absolute methanol; 8h is reacted when temperature is 45 ~ 65 DEG C; cooling; filter; solvent volatilization crystallization is controlled when 20 ~ 35 DEG C; obtain yellow transparent crystal, be 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound。Productivity: 72.4%。Fusing point: 254 ~ 255 DEG C (dec)。
Elementary analysis (C28H22N2O4Sn): value of calculation: C59.08, H3.90, N4.92;Measured value: C59.14, H3.86, N4.89。
FT-IR(KBr,ν/cm-1):3423,3055,3030,1591,1512,1490,1454,1325,1192,731,694,596,567,455。
1HNMR(500MHz,CD3Cl)δ(ppm):11.44(s,1H),8.19-8.21(dd,J1=8.1Hz,J2=1.7Hz,1H),7.76(m,4H),7.40-7.52(m,9H),7.28-7.29(m,2H),7.20-7.23(m,1H),7.00-7.04(m,2H),4.34(s,2H),1.26(s,2H)。
13CNMR(125MHz,CD3Cl)δ(ppm):175.89,162.97,160.97,155.28,136.04,135.49,134.96,133.34,131.73,130.9,129.59,129.47,129.11,127.49,119.51,117.91,114.76,33.56。
Embodiment 2:
The preparation of 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound:
The 100mL there-necked flask have nitrogen protection adds 0.344g (1.0mmol) diphenyl stannum dichloride, 0.152g (1.0mmol) salicylyl hydrazine, 0.195g (1.05mmol) Sodium.beta.-phenylpyruvate and 35mL solvent absolute methanol; 5h is reacted when temperature is 45 ~ 65 DEG C; cooling; filter; solvent volatilization crystallization is controlled when 20 ~ 35 DEG C; obtain yellow transparent crystal, be 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound。Productivity: 75.8%。Fusing point: 254 ~ 255 DEG C (dec)。
Elementary analysis (C28H22N2O4Sn): value of calculation: C59.08, H3.90, N4.92;Measured value: C59.14, H3.86, N4.89。
FT-IR(KBr,ν/cm-1):3423,3055,3030,1591,1512,1490,1454,1325,1192,731,694,596,567,455。
1HNMR(500MHz,CD3Cl)δ(ppm):11.44(s,1H),8.19-8.21(dd,J1=8.1Hz,J2=1.7Hz,1H),7.76(m,4H),7.40-7.52(m,9H),7.28-7.29(m,2H),7.20-7.23(m,1H),7.00-7.04(m,2H),4.34(s,2H),1.26(s,2H)。
13CNMR(125MHz,CD3Cl)δ(ppm):175.89,162.97,160.97,155.28,136.04,135.49,134.96,133.34,131.73,130.9,129.59,129.47,129.11,127.49,119.51,117.91,114.76,33.56。
Embodiment 3:
The preparation of 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound:
The 100mL there-necked flask have nitrogen protection adds 0.344g (1.0mmol) diphenyl stannum dichloride, 0.160g (1.05mmol) salicylyl hydrazine, 0.214g (1.15mmol) Sodium.beta.-phenylpyruvate and 30mL solvent absolute methanol; 15h is reacted when temperature is 45 ~ 65 DEG C; cooling; filter; solvent volatilization crystallization is controlled when 20 ~ 35 DEG C; obtain yellow transparent crystal, be 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound。Productivity: 74.6%。Fusing point: 254 ~ 255 DEG C (dec)。
Elementary analysis (C28H22N2O4Sn): value of calculation: C59.08, H3.90, N4.92;Measured value: C59.14, H3.86, N4.89。
FT-IR(KBr,ν/cm-1):3423,3055,3030,1591,1512,1490,1454,1325,1192,731,694,596,567,455。
1HNMR(500MHz,CD3Cl)δ(ppm):11.44(s,1H),8.19-8.21(dd,J1=8.1Hz,J2=1.7Hz,1H),7.76(m,4H),7.40-7.52(m,9H),7.28-7.29(m,2H),7.20-7.23(m,1H),7.00-7.04(m,2H),4.34(s,2H),1.26(s,2H)。
13CNMR(125MHz,CD3Cl)δ(ppm):175.89,162.97,160.97,155.28,136.04,135.49,134.96,133.34,131.73,130.9,129.59,129.47,129.11,127.49,119.51,117.91,114.76,33.56。
Embodiment 4:
The preparation of 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound:
The 250mL there-necked flask have nitrogen protection adds 1.720g (5.0mmol) diphenyl stannum dichloride, 0.775g (5.1mmol) salicylyl hydrazine, 1.004g (5.4mmol) Sodium.beta.-phenylpyruvate and 100mL solvent absolute methanol; 20h is reacted when temperature is 45 ~ 65 DEG C; cooling; filter; solvent volatilization crystallization is controlled when 20 ~ 35 DEG C; obtain yellow transparent crystal, be 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound。Productivity: 73.2%。Fusing point: 254 ~ 255 DEG C (dec)。
Elementary analysis (C28H22N2O4Sn): value of calculation: C59.08, H3.90, N4.92;Measured value: C59.14, H3.86, N4.89。
FT-IR(KBr,ν/cm-1):3423,3055,3030,1591,1512,1490,1454,1325,1192,731,694,596,567,455。
1HNMR(500MHz,CD3Cl)δ(ppm):11.44(s,1H),8.19-8.21(dd,J1=8.1Hz,J2=1.7Hz,1H),7.76(m,4H),7.40-7.52(m,9H),7.28-7.29(m,2H),7.20-7.23(m,1H),7.00-7.04(m,2H),4.34(s,2H),1.26(s,2H)。
13CNMR(125MHz,CD3Cl)δ(ppm):175.89,162.97,160.97,155.28,136.04,135.49,134.96,133.34,131.73,130.9,129.59,129.47,129.11,127.49,119.51,117.91,114.76,33.56。
Embodiment 5:
The preparation of 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound:
The 250mL there-necked flask have nitrogen protection adds 1.720g (5.0mmol) diphenyl stannum dichloride, 0.790g (5.2mmol) salicylyl hydrazine, 1.042g (5.6mmol) Sodium.beta.-phenylpyruvate and 150mL solvent absolute methanol; 22h is reacted when temperature is 45 ~ 65 DEG C; cooling; filter; solvent volatilization crystallization is controlled when 20 ~ 35 DEG C; obtain yellow transparent crystal, be 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound。Productivity: 74.4%。Fusing point: 254 ~ 255 DEG C (dec)。
Elementary analysis (C28H22N2O4Sn): value of calculation: C59.08, H3.90, N4.92;Measured value: C59.14, H3.86, N4.89。
FT-IR(KBr,ν/cm-1):3423,3055,3030,1591,1512,1490,1454,1325,1192,731,694,596,567,455。
1HNMR(500MHz,CD3Cl)δ(ppm):11.44(s,1H),8.19-8.21(dd,J1=8.1Hz,J2=1.7Hz,1H),7.76(m,4H),7.40-7.52(m,9H),7.28-7.29(m,2H),7.20-7.23(m,1H),7.00-7.04(m,2H),4.34(s,2H),1.26(s,2H)。
13CNMR(125MHz,CD3Cl)δ(ppm):175.89,162.97,160.97,155.28,136.04,135.49,134.96,133.34,131.73,130.9,129.59,129.47,129.11,127.49,119.51,117.91,114.76,33.56。
Embodiment 6:
The preparation of 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound:
The 250mL there-necked flask have nitrogen protection adds 3.440g (10.0mmol) diphenyl stannum dichloride, 1.550g (10.2mmol) salicylyl hydrazine, 1.972g (10.6mmol) Sodium.beta.-phenylpyruvate and 150mL solvent absolute methanol; 24h is reacted when temperature is 45 ~ 65 DEG C; cooling; filter; solvent volatilization crystallization is controlled when 20 ~ 35 DEG C; obtain yellow transparent crystal, be 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound。Productivity: 70.7%。Fusing point: 254 ~ 255 DEG C (dec)。
Elementary analysis (C28H22N2O4Sn): value of calculation: C59.08, H3.90, N4.92;Measured value: C59.14, H3.86, N4.89。
FT-IR(KBr,ν/cm-1):3423,3055,3030,1591,1512,1490,1454,1325,1192,731,694,596,567,455。
1HNMR(500MHz,CD3Cl)δ(ppm):11.44(s,1H),8.19-8.21(dd,J1=8.1Hz,J2=1.7Hz,1H),7.76(m,4H),7.40-7.52(m,9H),7.28-7.29(m,2H),7.20-7.23(m,1H),7.00-7.04(m,2H),4.34(s,2H),1.26(s,2H)。
13CNMR(125MHz,CD3Cl)δ(ppm):175.89,162.97,160.97,155.28,136.04,135.49,134.96,133.34,131.73,130.9,129.59,129.47,129.11,127.49,119.51,117.91,114.76,33.56。
Test example:
2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide the coordination compound of the present invention, its Anticancer Activity in vitro is measured and is realized by MTT experiment method。
MTT analytic process:
Based on metabolism reduction 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide。Succinate dehydrogenase in living cells mitochondrion can make exogenous MTT be reduced to water-insoluble bluish violet crystallization first a ceremonial jade-ladle, used in libation (Formazan) and be deposited in cell, and dead cell is without this function。First a ceremonial jade-ladle, used in libation in dimethyl sulfoxide (DMSO) energy dissolved cell, measures the optical density of characteristic wavelength, can indirectly reflect living cells quantity by microplate reader。
Mtt assay is adopted to measure the 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound of the embodiment 1 preparation inhibitory activity to human colon cancer cell (Colo205), human liver cancer cell (HepG2), human breast cancer cell (MCF7), human cervical carcinoma cell (Hela) and human lung carcinoma cell (NCI-H460)。
Cell strain and cultivating system: Colo205, HepG2, MCF7, Hela and NCI-H460 cell strain take from American. tissue incubator (ATCC)。RPMI1640(GIBICO company with containing 10% hyclone) culture medium, in 5%(volume fraction) CO2, carry out In vitro culture in 37 DEG C of saturated humidity incubators。
Test process: being added separately in each hole by test medicinal liquid (0.1ng/mL ~ 10ug/mL) according to the Concentraton gradient of concentration, each concentration sets 6 parallel holes。Experiment is divided into drug study group (being separately added into the test medicine of variable concentrations), matched group (only adding culture fluid and cell, be not added with test medicine) and blank group (only adding cultivation medicine, be not added with cell and test medicine)。Orifice plate after dosing is placed in 37 DEG C, 5%CO2Incubator is cultivated 72h。The activity of control drug measures according to the method for test sample。In orifice plate after having cultivated 72h, every hole adds MTT40uL(D-Hanks buffer and is made into 4mg/mL)。After placing 4h at 37 DEG C, remove the supernatant。Every hole adds 150uLDMSO, and vibrate 5min, makes Formazan crystallization dissolve。Finally, automatic microplate reader is utilized to detect the optical density in each hole at 570nm wavelength place。
Data process: data process and use GraphPadPrismversion5.0 program, coordination compound IC50It is fitted obtaining by program has the nonlinear regression model (NLRM) of S shape dose response。
With MTT analytic process, human colon cancer cell (Colo205), human liver cancer cell (HepG2), human breast cancer cell (MCF7), human cervical carcinoma cell (Hela) and human lung carcinoma cell (NCI-H460) cell strain are analyzed, measure its IC50Value, result is as shown in table 1, conclusion is: from data in table, it is used as cancer therapy drug with the 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound of the present invention, human colon cancer cell (Colo205), human liver cancer cell (HepG2), human breast cancer cell (MCF7), human cervical carcinoma cell (Hela) and human lung carcinoma cell (NCI-H460) are had certain drug effect, can as the candidate compound of cancer therapy drug。
Table 12-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound cancer therapy drug external activity test data。
2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound prepared by all the other embodiments is with the mtt assay same test example of active anticancer method of testing to human colon cancer cell (Colo205), human liver cancer cell (HepG2), human breast cancer cell (MCF7), human cervical carcinoma cell (Hela) and human lung carcinoma cell (NCI-H460), and test result is essentially identical with table 1。
Claims (8)
1. a 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound, for the coordination compound of following structural formula (I):
(I)
Wherein Ph is phenyl。
2. as claimed in claim 1 containing a kind of 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound, its ir data: FT-IR (KBr, ν/cm-1): 3423,3055,3030,1591,1512,1490,1454,1325,1192,731,694,596,567,455;Its nuclear-magnetism modal data:1HNMR(500MHz,CD3Cl)δ(ppm):11.44(s,1H),8.19-8.21(dd,J1=8.1Hz,J2=1.7Hz, 1H), 7.76 (m, 4H), 7.40-7.52 (m, 9H), 7.28-7.29 (m, 2H), 7.20-7.23 (m, 1H), 7.00-7.04 (m, 2H), 4.34 (s, 2H), 1.26 (s, 2H);13CNMR(125MHz,CD3Cl)δ(ppm):175.89,162.97,160.97,155.28,136.04,135.49,134.96,133.34,131.73,130.9,129.59,129.47,129.11,127.49,119.51,117.91,114.76,33.56。
3. described in claim 1,2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound has certain thermally-stabilised scope, can stable existence below 254 DEG C。
4. the preparation method of the 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound described in claim 1; it is characterized in that adding diphenyl stannum dichloride, salicylyl hydrazine, Sodium.beta.-phenylpyruvate and solvent absolute methanol in the reaction vessel have nitrogen protection; 5 ~ 24h is reacted when temperature is 45 ~ 65 DEG C; cooling; filter; control solvent volatilization crystallization when 20 ~ 35 DEG C, obtain yellow transparent crystal, be 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound。
5. the method for preparation as claimed in claim 4, it is characterised in that described diphenyl stannum dichloride, salicylyl hydrazine, Sodium.beta.-phenylpyruvate three amount of substance ratio for 1:(1 ~ 1.05): (1.05 ~ 1.15)。
6. the method for preparation as claimed in claim 4, it is characterised in that described solvent absolute methanol consumption be every mM of diphenyl stannum dichloride add 15 ~ 35 milliliters。
7. 2-carbonyl-3-phenylpropionic acid salicyloyl hydrazone stannous phenide coordination compound application in preparing cancer therapy drug described in claim 1。
8. the application described in claim 7, wherein said cancerous cell is human colon cancer cell, human liver cancer cell, human breast cancer cell, human cervical carcinoma cell, human lung carcinoma cell。
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