CN117551137A - 2,2':6', 2' -terpyridine derivative dinuclear platinum complex and synthetic method and application thereof - Google Patents
2,2':6', 2' -terpyridine derivative dinuclear platinum complex and synthetic method and application thereof Download PDFInfo
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- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 title claims abstract description 77
- 229910052697 platinum Inorganic materials 0.000 title claims abstract description 32
- 238000010189 synthetic method Methods 0.000 title description 3
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- 229940079593 drug Drugs 0.000 claims abstract description 8
- 238000001308 synthesis method Methods 0.000 claims abstract description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 39
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 229910052751 metal Inorganic materials 0.000 claims description 8
- 239000002184 metal Substances 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 7
- DBZAKQWXICEWNW-UHFFFAOYSA-N 2-acetylpyrazine Chemical compound CC(=O)C1=CN=CC=N1 DBZAKQWXICEWNW-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
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- 238000001914 filtration Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 238000001291 vacuum drying Methods 0.000 claims description 6
- DRGAZIDRYFYHIJ-UHFFFAOYSA-N 2,2':6',2''-terpyridine Chemical class N1=CC=CC=C1C1=CC=CC(C=2N=CC=CC=2)=N1 DRGAZIDRYFYHIJ-UHFFFAOYSA-N 0.000 claims description 5
- CXXCXICUGGOJPU-UHFFFAOYSA-N 1-(4-formylphenyl)piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1C1=CC=C(C=O)C=C1 CXXCXICUGGOJPU-UHFFFAOYSA-N 0.000 claims description 3
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- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 3
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
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- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
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- JFJNVIPVOCESGZ-UHFFFAOYSA-N 2,3-dipyridin-2-ylpyridine Chemical class N1=CC=CC=C1C1=CC=CN=C1C1=CC=CC=N1 JFJNVIPVOCESGZ-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
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- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
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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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System compounds of the platinum group
- C07F15/0086—Platinum compounds
- C07F15/0093—Platinum compounds without a metal-carbon linkage
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- 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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- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
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Abstract
The invention discloses a 2,2':6', 2' -terpyridine derivative binuclear platinum complex, a synthesis method and application thereof. The invention synthesizes a binuclear platinum complex with potential anticancer effect by taking 4 '-substituted-2, 2':6', 2' -terpyridine derivative as an active ligand. The 2,2':6', 2' -terpyridine derivative binuclear platinum complex has better inhibition effect on ovarian cancer drug-resistant strain cells SK-OV-3CR, is higher than cisplatin drugs, overcomes the drug resistance of clinical drugs, has potential medicinal value, and is expected to be used for preparing various antitumor drugs. The 2,2' -terpyridine derivative binuclear platinum complex can inhibit the growth of SKO3cisR in a targeted manner, has good anticancer activity and tumor targeting, shows excellent in-vitro and in-vivo antitumor activity, has potential medicinal value, and is expected to be used for preparing various antitumor drugs.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to a 2,2':6', 2' -terpyridine derivative binuclear platinum complex, a preparation method and application thereof.
Background
Cancer is generally treated by various methods such as radiation therapy, operation, chemotherapy and the like, but only the operation therapy and the radiation therapy are one of the important means of local treatment, while platinum drugs inhibit the growth of tumor cells during the chemotherapy, and simultaneously have toxic effects to various cells which normally proliferate in the organism to different degrees. Therefore, development and treatment of the targeting non-platinum drugs have shown a better prospect (Guo, Z.; et al chem. Soc. Rev.; 2013,42: 202-224.) in recent years, but at present, clinical application needs further deep observation and accumulation in the clinical trial stage, so that the development and treatment have a larger gap from large-scale clinical popularization and application.
At present, clinical cisplatin and derivatives generate serious adverse reactions, including nephrotoxicity, drug resistance and the like. Therefore, researchers are urgently required to develop a targeted, efficient and low-toxicity platinum anticancer complex.
In recent years, a large number of terpyridine derivative metal complexes are reported successively, and the complexes have good anticancer activity, but the complexes with targeting property are still deficient.
Disclosure of Invention
It is an object of the present invention to provide 2,2':6',2 "-terpyridine derivative dinuclear platinum complexes having potential anticancer effects.
The invention provides a 2,2':6', 2' -terpyridine derivative binuclear platinum complex, the chemical formula of which is [ Pt ] 2 (tpy1)(DMSO) 2 Cl 4 ]·CH 3 OH (tpy 1 Pt) having the chemical formula:
it is another object of the present invention to provide a method for synthesizing the above-mentioned binuclear platinum complex of 2,2':6',2 "-terpyridine derivative.
Specifically, the synthesis method comprises the following steps: 2-acetylpyrazine, 1- (4-formylphenyl) piperidine-4-carboxylic acid, absolute ethyl alcohol, KOH and ammonia water, and stirring and reacting for 48.0h at 55 ℃ to obtain a white ligand 2,2':6', 2' -terpyridine derivative tpy1; ligand tpy1, metal salt cis-Pt (DMSO) 2 Cl 2 Anhydrous CH 3 And (3) carrying out coordination reaction on OH and acetone at 45-80 ℃ for 3 days, filtering, and drying in a vacuum drying oven at 45 ℃ to obtain yellow massive crystals tpy1Pt.
The synthetic route is as follows:
the synthesis temperature of the binuclear platinum complex tpy1Pt of the invention must be 45-80 ℃, if the synthesis temperature exceeds 80 ℃, the pipe is burnt completely, the yield is low, if the synthesis temperature is lower than 45 ℃, almost no product is generated, the yield is extremely low, the separation is difficult, after the optimized condition, the reaction system reacts at 80 ℃, and the target product obtained by the system is 88.4 percent at the highest.
The reaction of the present invention must contain a mixed solution of acetone and methanol in a total volume of 1.5-10.0mL, too low impurities, too high yields, and very low yields, and wherein the mixed solution contains 3.5mL of anhydrous CH 3 OH andthe reaction condition was the highest yield at 0.5mL of acetone. Without acetone, little product is produced; without methanol, the byproducts are relatively large, and the separation and the treatment are difficult.
The reaction days are 3 days, and the product is relatively pure and easy to separate. Over 3 days, the quality of the product is not increased any more.
A third object of the present invention provides the use of the above-mentioned 2,2':6', 2' -terpyridine derivative dinuclear platinum complex.
In particular to application of 2,2':6', 2' -terpyridine derivative binuclear platinum complex in preparing targeted medicaments for treating ovarian cancer. Further relates to application of the 2,2':6', 2' -terpyridine derivative binuclear platinum complex in preparing medicaments for targeted treatment of ovarian cancer of drug-resistant strains.
Compared with the prior art, the invention synthesizes the binuclear platinum complex [ Pt ] with potential anticancer effect by taking the 4 '-substituted-2, 2':6', 2' -terpyridine derivative tpy1 as an active ligand 2 (tpy1)(DMSO) 2 Cl 4 ]·CH 3 OH (tpy 1 Pt) and examined their activity and toxicity experiments on human ovarian cancer SK-OV-3 (SKO 3) and cisplatin-resistant strain SK-OV-3/DDP (SKO 3 cisR) and normal HL-7702 cells. Experimental results show that tpy1Pt targets to inhibit proliferation of human ovarian cancer SKO3cisR and IC thereof 50 The value is 0.23+/-0.08 mu M, and the activity is far greater than that of the ligand tpy1, cis-Pt (DMSO) 2 Cl 2 And clinical medicine cisplatin, and its inhibition to normal HL-7702 cell is very small>50.0 mu M), the binuclear platinum complex tpy1Pt can inhibit the growth of SKO3cisR in a targeted manner, and has good anticancer activity and tumor targeting. More importantly, in vivo tumor inhibition experiments show that SKO3cisR has good tumor inhibition effect on a nude mouse model of human ovarian cancer SKO3, and the inhibition rate is up to 52.4 percent, which is higher than the inhibition effect (50.0 percent) of clinical medicine cisplatin. In a word, the binuclear platinum complex tpy1Pt shows excellent in-vitro and in-vivo antitumor activity, has potential medicinal value, and is expected to be used for preparing various antitumor drugs.
Drawings
FIG. 1 is a hydrogen nuclear magnetic resonance spectrum of ligand tpy1 prepared in example 1 of the present invention;
FIG. 2 is a nuclear magnetic resonance carbon spectrum of ligand tpy1 prepared in example 1 of the present invention;
FIG. 3 is a diagram showing the structure of an X-ray single crystal of a binuclear platinum complex tpy1Pt prepared in example 1 of the present invention;
FIG. 4 is a nuclear magnetic resonance hydrogen spectrum of a binuclear platinum complex tpy1Pt prepared in example 1 of the present invention.
Detailed Description
The present invention will be further illustrated by the following specific examples, but the present invention is not limited to these examples.
The metal salt cis-Pt (DMSO) involved in the synthesis method of the invention 2 Cl 2 The preparation can be carried out with reference to the prior art (Al-Allaf, T.A.K.; et Al Transit.Met.chem.,1998, 23:403-406.).
Example 1
(a) The ligand tpy1 is synthesized by the synthetic method of the reference (K.Czerwi ń ska, B.Machura, S.Kula, S.Krompiec, K.Erfurt, C.Roma-Rodrigues, A.R.Fernandes, L.S.Shul 'pina, N.S. Ikonnikov and G.B. Shul' pin, dalton Trans.,2017,46,9591-9604.): in a 250mL round bottom flask, 12.0mmol of 2-acetylpyrazine, 6.0mmol of 1- (4-formylphenyl) piperidine-4-carboxylic acid, 55.0mL of absolute ethyl alcohol, 25.0mmol of KOH and 100.0mmol of ammonia water (25% -28%) are added, stirred at 55 ℃ for reaction for 48.0H, white solid is precipitated, and the mixture is filtered by suction, and H is used for the reaction 2 O (25.0 mL) and EtOH (10.0 mL) were each washed once, and then the final white ligand tpy1 was obtained (yield: 68.4%).
(b) Into a 15.0mL high temperature pressure tube, 0.1mmol of ligand tpy1 and 0.2mmol of metal salt cis-Pt (DMSO) were added 2 Cl 2 3.5mL of anhydrous CH 3 OH and 0.5mL of acetone, carrying out coordination reaction for 3.0 days at 80 ℃, filtering, and drying in a vacuum drying oven at 45 ℃ to obtain yellow massive crystals tpy1Pt. The yield was 88.4%.
The product obtained was identified:
(1) The nuclear magnetic resonance hydrogen spectrum of the ligand tpy1 is shown in figure 1.
1 H NMR(400MHz,DMSO-d 6 )δ9.86(s,2H),8.81(d,J＝9.8Hz,4H),8.65(s,2H),7.83(d,J＝7.6Hz,2H),7.11(d,J＝9.0Hz,2H),3.81(d,J＝10.1Hz,2H),2.90(d,J＝8.6Hz,1H),1.92(d,J＝10.8Hz,2H),1.64(d,J＝11.0Hz,2H).
(2) FIG. 2 is a nuclear magnetic resonance carbon spectrum of ligand tpy1 prepared in example 1 of the present invention.
13 C NMR(101MHz,DMSO-d 6 )δ175.11,155.30,152.16,151.61,145.33,144.39,143.02,138.41,127.68,117.53,115.40,47.04,40.05,39.52,27.30.
(3) Infrared spectrum results for ligand tpy 1.
IR(KBr):3417,3047,2933,2820,2517,1936,1719,1600,1521,1471,1448,1432,1378,1307,1292,1255,1202,1171,1119,1033,934,855,821,760,740,614,576,526,488,406cm -1 .
(4) The elemental analysis results are shown in table 1.
Table 1 elemental analysis results for ligand tpy1 and Complex tpy1Pt in the examples
(5) The X-ray single crystal structure diagram of the complex tpy1Pt is shown in FIG. 3.
(6) The nuclear magnetic resonance hydrogen spectrum of the complex tpy1Pt is shown in fig. 4.
1 H NMR(400MHz,DMSO-d 6 )δ12.28(s,1H),9.83(s,2H),8.79(dd,J＝10.9,7.0Hz,4H),8.61(s,2H),7.80(d,J＝8.6Hz,2H),7.08(d,J＝8.7Hz,2H),3.81(d,J＝12.4Hz,2H),2.90(d,J＝6.6Hz,2H),2.73(s,1H),2.54(s,12H),1.93(d,J＝11.5Hz,2H),1.64(dd,J＝23.4,11.9Hz,2H).
(7) Infrared spectrum results of the complex tpy1Pt.
IR(KBr):3934,3424,3097,3011,2954,2919,1722,1660,1598,1581,1520,1469,1435,1377,1315,1256,1204,1181,1137,1110,1059,1026,998,930,882,845,822,733,690,614,576,550,508,496,471,440,417,407cm -1 .
(8) The elemental analysis results are shown in table 1.
Thus, the resulting ligand tpy1 and complex tpy1Pt can be determined as follows:
example 2
Into a 15.0mL high temperature pressure tube, 0.1mmol of ligand tpy1, 0.2mmol of metal salt cis-Pt (DMSO) was added 2 Cl 2 1.0mL of anhydrous CH 3 OH and 2.5mL of acetone, carrying out coordination reaction for 3.0 days at 45 ℃, filtering, and drying in a vacuum drying oven at 45 ℃ to obtain yellow massive crystals tpy1Pt. The yield was 70.2%.
Example 3
Into a 15.0mL high temperature pressure tube, 0.1mmol of ligand tpy1, 0.2mmol of metal salt cis-Pt (DMSO) was added 2 Cl 2 2.5mL of anhydrous CH 3 OH and 1.5mL of acetone, carrying out coordination reaction for 3.0 days at 60 ℃, filtering, and drying in a vacuum drying oven at 45 ℃ to obtain yellow massive crystals tpy1Pt. The yield was 78.4%.
Example 4
Into a 15.0mL high temperature pressure tube, 0.1mmol of ligand tpy1, 0.2mmol of metal salt cis-Pt (DMSO) was added 2 Cl 2 5.5mL of anhydrous CH 3 OH and 0.5mL of acetone, carrying out coordination reaction for 3.0 days at 50 ℃, filtering, and drying in a vacuum drying oven at 45 ℃ to obtain yellow massive crystals tpy1Pt. The yield was 80.0%.
In order to fully illustrate the application of the binuclear platinum complex tpy1Pt in pharmacy, the inventor performs in-vitro and in-vitro anti-tumor activity experiments.
1. Proliferation inhibition activity experiment of binuclear platinum complex tpy1Pt on three human cell lines
1. Cell strain and cell culture
The experiment selects 3 human cell lines such as human ovarian cancer SK-OV-3 (SKO 3) and cisplatin-resistant strain SK-OV-3/DDP (SKO 3 cisR) and normal HL-7702 cells.
All the humanized cell lines were cultured inIn RPMI-1640 culture solution containing 100U/mL penicillin, 10wt% calf blood and 100U/mL streptomycin, placing the culture solution at 37deg.C and containing 5% CO by volume 2 Culturing in incubator.
2. Preparation of test Compounds
All compounds used were required to have a purity of 95.0% or more, their DMSO stock was diluted with physiological buffer to a final solution of 40. Mu. Mol/L (final concentration of DMSO 1.0%) and the extent of inhibition of each compound at this concentration on growth of normal cells or selected tumor cells was tested.
3. Cell growth inhibition experiment (CCK-8 method)
(1) Cell digestion, counting and concentration of 5X 10 4 mu.L of cell suspension was added per well to each of the 96-well cell culture plates per mL of cell suspension.
(2) 96-well cell culture plates were placed at 37℃with 5% CO 2 Culturing in an incubator for 24 hours.
(3) The drug was diluted to the desired concentration with complete medium, 100 μl of the corresponding drug-containing medium was added per well, while a negative control group was established.
(4) 96-well cell culture plates were placed at 37℃with 5% CO 2 Culturing in an incubator for 48 hours.
(5) CCK-8 staining was performed, λ=450 nm, and OD values were determined.
i) 10 mu L of CCK-8 is added into each hole, and the culture is continued for 2 hours in an incubator;
ii) gently mixing the mixture for 10min on a shaking table;
iii) Lambda=450 nm, the OD value of each well is read by an enzyme labeling instrument, and the number of living cells is judged according to the measured optical density value (OD value), and the larger the OD value is, the stronger the cell activity is. Using the formula:
calculating the inhibition rate of each compound on the growth of the selected cells, and calculating the IC of each tested compound on each selected cell strain by using a Bliss method 50 Values. The results are shown in Table 2 below.
TABLE 2 Compound pairsIC of cell lines 50 Value (mu M)
IC from Table 2 50 As can be seen from the results of the activity screening, tpy1Pt targets to inhibit proliferation of SKO3cisR, a human ovarian cancer, IC 50 The value is 0.23+/-0.08 mu M, and the activity is far greater than that of the ligand tpy1, cis-Pt (DMSO) 2 Cl 2 And clinical medicine cisplatin, and its inhibition to normal HL-7702 cell is very small>50.0 mu M), the binuclear platinum complex tpy1Pt can inhibit the growth of SKO3cisR in a targeted manner, and has good anticancer activity and tumor targeting.
2. In vivo tumor inhibition experiment of tumor-bearing nude mice
Collecting human ovarian cancer SKO3 in logarithmic growth phase, and preparing into 5×10 with serum-free culture medium cells 6 individual/mL viable cell concentration suspension. 0.2mL of the suspension was withdrawn using a 1.0mL syringe containing about 1X 10 7 The living cells are inoculated under the skin of the right armpit of the nude mouse until the subcutaneous tumor grows to about 1cm 3 At this time, as a tumor source for subcutaneous tumor model preparation, the mice were passaged. Transferring 4 generations of human ovarian cancer SKO3 on nude mice, selecting tumor-bearing mice with vigorous tumor growth and no ulcer, killing cervical vertebra dislocation, sterilizing animal skin with 75.0% medical alcohol, dissecting tissue block, removing necrotic part, cutting tumor tissue into 1.5mm 3 Left and right small pieces were inoculated subcutaneously in the right armpit of nude mice with a trocar. Measuring the diameter of transplanted tumor by using an electronic vernier caliper, and when the tumor volume grows to 100-300mm 3 At that time, animals were randomly grouped.
Nude mice bearing human ovarian carcinoma SKO3 tumor were randomly divided into vehicle group, tpy1Pt dosing group and blank control group, each group of 6 animals. Intraperitoneal administration was started on the day of grouping, once every 1 day. The tumor diameter and the body weight are measured by an electronic vernier caliper every three days. Cervical dislocation was sacrificed on day 21, tumors were dissected, weighed, photographed, and tumor suppression rates were calculated.
Tumor volume calculation formula: v=a×b 2 2, wherein a is a long diameter and b is a short diameter;
relative tumor volume rtv=v t /V 0 Wherein V is t For the volume at each measurement, V 0 Is the volume when grouped;
relative tumor proliferation rate T/C% = (T RTV /C RTV )×100％；
Tumor growth inhibition (%) = (mean tumor weight in vehicle group-mean tumor weight in treatment group)/mean tumor weight in vehicle group x 100%.
TABLE 3 in vivo tumor inhibition of ovarian cancer SKO3 tumor bearing nude by binuclear Complex tpy1Pt
From the in vivo tumor inhibition experiments in Table 3, the tpy1Pt has good tumor inhibition effect on a nude mouse model carrying human ovarian cancer SKO3, and the inhibition rate is up to 52.4 percent, which is far higher than the inhibition effect (50.0 percent) of clinical medicine cisplatin. In which cisplatin in vivo anticancer data are derived from literature related reports (J.Qi, Y.Zheng, B.Li, L.Wei, J.Li, X.Xu, S.Zhao, X.Zheng and Y.Wang, eur.J.Med.Chem.,2022,237,114415.), studies have also found that the binuclear platinum complex tpy1Pt has no effect on the body weight of nude mice, nor injure organs such as viscera and kidneys of mice. In a word, the binuclear platinum complex tpy1Pt shows excellent in-vivo anti-tumor activity, has potential medicinal value, and is expected to be used for preparing various anti-tumor medicaments.
Claims (6)
1. A2, 2':6', 2' -terpyridine derivative binuclear platinum complex is characterized by having a chemical structural formula as shown in the specification:
2.2,2':6',2 '-terpyridine derivative binuclear platinum complex synthesis method, which is characterized in that 2-acetylpyrazine, 1- (4-formylphenyl) piperidine-4-carboxylic acid, absolute ethyl alcohol, KOH and ammonia water are stirred and reacted for 48.0h at 55 ℃ to obtain 2,2':6', 2' -terpyridine derivative, namely ligand tpy1; the ligand tpy1, metal salt cis-Pt (DMSO) 2 Cl 2 Anhydrous CH 3 Carrying out coordination reaction on OH and acetone at 45-80 ℃ for 3 days, filtering, and drying in a vacuum drying oven at 45 ℃ to obtain the catalyst.
3. The method for synthesizing a 2,2':6',2 "-terpyridine derivative dinuclear platinum complex according to claim 2, wherein the total volume of the mixed solution of anhydrous acetone and methanol is 1.5-10.0mL.
4. The method for synthesizing a binuclear platinum complex as defined in claim 3, wherein said anhydrous CH is 3 OH was 3.5mL and acetone was 0.5mL.
5. Use of a binuclear platinum complex of a 2,2':6',2 "-terpyridine derivative according to claim 1 in the preparation of a medicament for targeted treatment of ovarian cancer.
6. Use of a binuclear platinum complex of a 2,2':6',2 "-terpyridine derivative in the preparation of a medicament for targeted treatment of ovarian cancer of drug-resistant strains according to claim 1.
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