CN114315913B - Pt (II) complex with anti-tumor activity and preparation method and application thereof - Google Patents
Pt (II) complex with anti-tumor activity and preparation method and application thereof Download PDFInfo
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Abstract
The application discloses a Pt (II) complex with anti-tumor activity, which comprises the following components: the Pt (II) complex takes benzothiazole functionalized nitrogen heterocyclic carbene compound as a ligand, and a central platinum atom is of a four-coordination structure, wherein one of the cationic structural formulas is as follows:the application also discloses a preparation method of the Pt (II) complex with the anti-tumor activity and application of the Pt (II) complex with the anti-tumor activity in medicines for treating cervical cancer, human colon cancer, human ovarian clear cell carcinoma and liver cancer. The complex has the advantages of changeable structure, convenient synthesis, stable performance and environmental protection, can exist stably in the air for a long time, has strong inhibition effect on the growth of tumor cells, and can be used as a medicine for treating tumors.
Description
Technical Field
The application relates to the technical field of biological medicines, in particular to a Pt (II) complex with anti-tumor activity, and a preparation method and application thereof.
Background
Cancer is one of the most leading causes of death in humans, and the development of antitumor drugs has been a global major topic faced by humans. Cisplatin with anticancer activity was first reported by Rosenberg et al in 1965 (cis- [ Pt (NH 3) 2 Cl 2 ]) Thus, a new field of pharmaceutical inorganic chemistry is created. Cisplatin is a legged old man in the field of anticancer drugs, and has been approved by the FDA for the treatment of prostate cancer and lymphoma since 1978 and has been widely used clinically for over 40 years. Cisplatin is also used to treat various tumors such as lung cancer, cervical cancer, ovarian cancer, etc., and it is estimated that at least 50% of tumor patients receive treatment with platinum-based anticancer drugs. The discovery and application of cisplatin have milestone significance for the development of tumor chemotherapy, and are known as penicillin in the field of antitumor drugs.
Cisplatin has achieved great success in the treatment of cancer, but has poor water solubility, low oral activity and strong toxic and side effects, such as nephrotoxicity, ototoxicity and neurotoxicity, which can be caused by large-dose or continuous administration. In order to overcome the clinical defects of cisplatin, reduce toxicity and improve drug resistance, a series of platinum compounds are researched. The mechanism of cisplatin resistance is complex and has not yet been fully elucidated. If DNA damage caused by cisplatin is discovered by DNA repair mechanisms and activates DNA repair pathways, or DNA damage is completely repaired, cisplatin will lose its efficacy, which is one of the important mechanisms by which cells develop cisplatin resistance. Therefore, research and development of novel platinum drugs to improve cisplatin resistance has attracted considerable attention from researchers.
The antitumor drugs taking the metal complexes as the research objects have breakthrough progress in design routes and synthetic methods, and mainly comprise platinum complexes, copper complexes, ruthenium complexes and the like. The application takes benzothiazole functional N-heterocyclic carbene (NHC) as a ligand to synthesize Pt (II) compound and researches the anti-tumor activity of the Pt (II) compound so as to screen out high-efficiency and low-toxicity anti-tumor drugs.
Disclosure of Invention
The application aims to provide a Pt (II) complex with anti-tumor activity, and a preparation method and application thereof, so as to solve the problems in the prior art.
In order to achieve the above purpose, the present application provides the following technical solutions: the Pt (II) complex takes benzothiazole functionalized N-heterocyclic carbene compound as a ligand, a central platinum atom is of a four-coordination structure, and an anion of the Pt (II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halogen ion, wherein the structural formula of the cation is:
further, the Pt1 compound belongs to a triclinic system, the space group P-1, and the unit cell parameters are as follows: a= 7.5537 (3),α＝81.854(5)°,β＝88.595(4)°,γ＝69.934(5)°,/>
the Pt (II) complex takes benzothiazole functionalized N-heterocyclic carbene compound as a ligand, a central platinum atom is of a four-coordination structure, and an anion of the Pt (II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halogen ion, wherein the structural formula of the cation is:
further, the Pt2 compound belongs to the triclinic system, the P-1 space group, and the unit cell parameters are as follows: α＝82.225(3)°,β＝71.358(4)°,γ＝64.223(4)°,/>
the Pt (II) complex takes benzothiazole functionalized N-heterocyclic carbene compound as a ligand, a central platinum atom is of a four-coordination structure, and an anion of the Pt (II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halogen ion, wherein the structural formula of the cation is:
further, the Pt3 compound belongs to an orthorhombic system, the space group P-1, and the unit cell parameters are as follows: α＝90°,β＝90°,γ＝90°,/>
the Pt (II) complex takes benzothiazole functionalized N-heterocyclic carbene compound as a ligand, a central platinum atom is of a four-coordination structure, and an anion of the Pt (II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halogen ion, wherein the structural formula of the cation is:
further, the Pt4 compound belongs to the triclinic system, the P-1 space group, and the unit cell parameters are as follows: α＝89.725(5)°,β＝88.266(5)°,γ＝87.877(5)°,/>
the preparation method of the Pt (II) complex with the anti-tumor activity comprises the following steps:
in acetonitrile or acetone, which is an organic solvent, the molar ratio is 2:1 and silver oxide, reacting at 50 ℃ in the dark for 4-6 hours, filtering, adding Pt (COD) Cl into the filtrate 2 The molar ratio of the benzothiazole functionalized imidazole salt ligand to the benzothiazole functionalized imidazole salt ligand is 1:1, continuing to react for 2-4 hours at room temperature, filtering, and obtaining light yellow blocky crystals which are Pt (II) complexes through an diethyl ether volatilization method.
The application of Pt (II) complexes Pt1, pt2, pt3 and Pt4 with anti-tumor activity in preparing anti-tumor drugs is as follows: taking cancer cells in a growing period, digesting the cancer cells by pancreatin, incubating the plates for 24 hours at 37 ℃ to enable the cells to adhere to the walls, adding benzothiazole functionalized azacyclo-carbene platinum compounds and cisplatin cis-Pt (100 mu L/hole) prepared in examples 1-4 with different concentrations, adding 30 mu L of thiazole blue (MTT, 5 mg/mL) into each hole after culturing for 48 hours, removing the supernatant after culturing for 4 hours, adding 100 mu L of dimethyl sulfoxide (DMSO) into each hole, and oscillating to enable the crystallized products to be fully dissolved.
Compared with the prior art, the method has the following beneficial effects:
the compound prepared by the application has the advantages of changeable structure, convenient synthesis, stable performance and environmental protection, and can exist stably in the air for a long time.
The compound prepared by the application has strong inhibition effect on the growth of tumor cells and can be used as a medicine for treating tumors.
Drawings
FIG. 1 is a single crystal structure diagram of Pt (II) complex Pt1 cation;
FIG. 2 is a single crystal structure diagram of Pt (II) complex Pt2 cation;
FIG. 3 is a single crystal structure diagram of Pt (II) complex Pt3 cation;
FIG. 4 is a single crystal structure diagram of Pt (II) complex Pt4 cation;
FIG. 5 shows the Pt (II) complex Pt1 1 HNMR spectrogram;
FIG. 6 shows Pt (II) complex Pt1 13 CNMR spectrogram;
FIG. 7 shows Pt (II) complex Pt2 1 HNMR spectrogram;
FIG. 8 shows Pt (II) complex Pt2 13 CNMR spectrogram;
FIG. 9 shows Pt (II) complex Pt3 1 HNMR spectrogram;
FIG. 10 shows the Pt (II) complex Pt3 13 CNMR spectrogram;
FIG. 11 shows the Pt (II) complex Pt4 1 HNMR spectrogram;
FIG. 12 shows the Pt (II) complex Pt4 13 CNMR spectra；
FIG. 13 is a graph of cell survival of Pt (II) complexes versus cervical cancer Hela;
FIG. 14 is a graph of cell survival of Pt (II) complexes versus human colon carcinoma HCT 116;
FIG. 15 is a graph of cell survival of Pt (II) complexes versus human colon carcinoma HT-29;
FIG. 16 is a graph of cell survival of Pt (II) complexes against human ovarian clear cell carcinoma ES-2;
FIG. 17 is a graph showing cell survival of Pt (II) complex to liver cancer 7402.
Detailed Description
The following description of the embodiments of the present application will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present application, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the application without making any inventive effort, are intended to be within the scope of the application.
Referring to fig. 1-17, a Pt (II) complex with antitumor activity uses benzothiazole functionalized azacyclo-carbene compound as a ligand, a central platinum atom is in a four-coordination structure, and an anion of the Pt (II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halogen ion, wherein a cationic structural formula is:
a Pt (II) complex with antitumor activity, a Pt1 compound belongs to a triclinic system, a P-1 space group and the unit cell parameters are as follows: a= 7.5537 (3),α＝81.854(5)°,β＝88.595(4)°,γ＝69.934(5)°,/>
the Pt (II) complex takes benzothiazole functionalized N-heterocyclic carbene compound as a ligand, a central platinum atom is of a four-coordination structure, and an anion of the Pt (II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halogen ion, wherein the structural formula of the cation is:
a Pt (II) complex with antitumor activity, a Pt2 compound belongs to a triclinic system, a P-1 space group and the unit cell parameters are as follows:α＝82.225(3)°,β＝71.358(4)°,γ＝64.223(4)°,/>
a Pt (II) complex with antitumor activity, wherein the Pt (II) complex uses a benzothiazole functionalized nitrogen heterocyclic carbene compound as a ligand, a central platinum atom is of a four-coordination structure, and an anion of the Pt (II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halogen ion, wherein a cationic structural formula is:
a Pt (II) complex with antitumor activity, a Pt3 compound belongs to an orthorhombic system, a P-1 space group and unit cell parameters are as follows:α＝90°,β＝90°,γ＝90°,/>
the Pt (II) complex takes benzothiazole functionalized N-heterocyclic carbene compound as a ligand, a central platinum atom is of a four-coordination structure, and an anion of the Pt (II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halogen ion, wherein the structural formula of the cation is:
a Pt (II) complex with antitumor activity, a Pt4 compound belongs to a triclinic system, a P-1 space group and the unit cell parameters are as follows:α＝89.725(5)°,β＝88.266(5)°,γ＝87.877(5)°,/>
the preparation method of the Pt (II) complex with the anti-tumor activity comprises the following steps:
in acetonitrile or acetone, which is an organic solvent, the molar ratio is 2:1 and silver oxide, reacting at 50 ℃ in the dark for 4-6 hours, filtering, adding Pt (COD) Cl into the filtrate 2 The molar ratio of the benzothiazole functionalized imidazole salt ligand to the benzothiazole functionalized imidazole salt ligand is 1:1, continuing to react for 2-4 hours at room temperature, filtering, and obtaining light yellow blocky crystals which are Pt (II) complexes through an diethyl ether volatilization method.
The application of Pt (II) complexes Pt1, pt2, pt3 and Pt4 with anti-tumor activity in preparing anti-tumor drugs is as follows: taking cancer cells in a growing period, digesting the cancer cells by pancreatin, incubating the plates for 24 hours at 37 ℃ to enable the cells to adhere to the walls, adding benzothiazole functionalized azacyclo-carbene platinum compounds and cisplatin cis-Pt (100 mu L/hole) prepared in examples 1-4 with different concentrations, adding 30 mu L of thiazole blue (MTT, 5 mg/mL) into each hole after culturing for 48 hours, removing the supernatant after culturing for 4 hours, adding 100 mu L of dimethyl sulfoxide (DMSO) into each hole, and oscillating to enable the crystallized products to be fully dissolved.
The N-heterocyclic carbene platinum compound disclosed by the application has the advantages of variable structure, convenience in synthesis, stable performance and environment friendliness, can exist stably in the air for a long time, and the crystals prepared in the following examples 1 to 4 can be placed in the air without deterioration all the time, so that the N-heterocyclic carbene platinum compound has a wide application prospect in the pharmaceutical and fine chemical industries.
First embodiment: (preparation and performance of Pt (II) complex Pt 1) the reaction equation is as follows:
at 50℃adding ligand HL 1 PF 6 87.4mg (0.2 mmol), acetonitrile 5mL, silver oxide 23mg (0.1 mmol), and the mixture was reacted for 4 hours and filtered. Adding Pt (COD) Cl into the filtrate 2 74.8mg (0.2 mmol) of the mixture was reacted at room temperature for 2 hours, the mixture was centrifuged, the filtrate was concentrated to 2mL, diethyl ether was added to precipitate a yellow solid, the yellow solid was washed with diethyl ether for 2 times, then acetonitrile was used for dissolution, diethyl ether was slowly added, and recrystallization was carried out to obtain 73mg of benzothiazole-functionalized N-heterocyclic carbene ligand-coordinated platinum compound Pt1 in 48% yield. The diethyl ether volatilization method is used for obtaining the crystal of the Pt1 compound, and the single crystal structure is shown in figure 1.
The physicochemical properties of the Pt1 compound are as follows: pale yellow crystals, which are easily dissolved in acetonitrile, DMSO, DMF, etc., and whose nuclear magnetic resonance data are shown in fig. 5 and 6, are: 1 HNMR(400MHz,Acetone-d 6 )δ8.41(d,J＝8.0,1H),8.25(d,J＝8.0,1H),8.00(s,1H),7.80(t,J＝8.0,1H),7.67(t,J＝8.0,1H),7.48(s,1H),7.21(s,1H),4.77-4.84(m,2H),2.44(s,4H),1.40(d,J＝8.0,3H),1.26(d,J＝8.0,3H). 13 CNMR(100MHz,Acetone-d 6 )δ181.81,146.03,140.14,129.85,129.72,127.11,124.49,120.34,119.65,118.44,52.36,23.44,20.46。
specific embodiment II: (preparation and performance of Pt (II) complex Pt 2) the reaction equation is as follows:
at 50℃adding ligand HL 1 PF 6 87.4mg (0.2 mmol), acetonitrile 5mL, silver oxide 23mg (0.1 mmol), and the mixture was reacted for 4 hours and filtered. Adding Pt (COD) Cl into the filtrate 2 74.8mg (0.2 mmol) and 18mg (0.3 mmol) of acetic acid were reacted further for 2 hours at 50℃and centrifuged, the filtrate was concentrated to 2mL, diethyl ether was added to precipitate a yellow solid, the yellow solid was washed 2 times with diethyl ether and then with acetonitrile, diethyl ether was slowly added and recrystallized to give 53mg of benzothiazole-functionalized N-heterocyclic carbene ligand-coordinated platinum compound Pt2 in 39% yield. The diethyl ether volatilization method is used for obtaining the crystal of the Pt2 compound, and the single crystal structure is shown in figure 2.
The physicochemical properties of the Pt2 compound are as follows: pale yellow crystals, which are easily dissolved in solvents such as acetonitrile, DMSO, DMF, etc., and whose nuclear magnetic resonance data are shown in fig. 7 and 8, are: 1 HNMR(400MHz,CD 3 CN)δ8.36(d,J＝8.0,2H),8.09(d,J＝8.0,2H),7.94(t,J＝8.0,2H),7.72(t,J＝8.0,2H),7.39-7.41(m,6H),7.23(d,J＝4.0,2H),6.38-6.41(m,2H),5.34(d,J＝12.0,2H),4.51(d,J＝16.0,2H),2.33(s,4H),2.24(s,6H). 13 CNMR(100MHz,DMSO)δ182.33,146.03,133.91,129.71,129.12,128.82,127.59,124.46,123.93,119.54,104.99,52.90。
third embodiment: (preparation and performance of Pt (II) complex Pt 3) the reaction equation is as follows:
at 50℃adding ligand HL 1 PF 6 87.4mg (0.2 mmol), 5mL of acetone, 23mg (0.1 mmol) of silver oxide, reacted for 4 hours, and filtered. Adding Pt (COD) Cl into the filtrate 2 74.8mg (0.2 mmol) and the reaction was continued at room temperature for 2 hours, and the filtrate was concentrated to 2mL, and diethyl ether was added to precipitate a yellow solid, which was washed 2 times with diethyl ether. Then acetonitrile is used for dissolution, diethyl ether is slowly added, and the recrystallization is carried out to obtain 96mg of benzothiazole functionalized N-heterocyclic carbene ligand coordinated platinum compound Pt3, and the yield is 61%. The diethyl ether volatilization method is used for obtaining the crystal of the Pt3 compound, and the single crystal structure is shown in figure 3.
Pt3 compound, reasonThe chemical properties are as follows: pale yellow crystals, which are easily dissolved in solvents such as acetonitrile, DMSO, DMF, etc., and whose nuclear magnetic resonance data are shown in fig. 9 and 10, are: 1 HNMR(400MHz,CD 3 CN)δ8.18(d,J＝8.0,1H),8.12(d,J＝8.0,1H),8.07(s,1H),7.69(t,J＝8.0,1H),7.62(t,J＝8.0,1H),7.46-7.51(m,5H),7.41(s,1H),6.29-6.34(m,1H),6.17-6.22(m,1H),5.87(d,J＝16.0,1H),5.57(d,J＝16.0,1H),5.00-5.10(m,1H),4.87-4.97(m,1H),2.77-2.86(m,1H),2.63-2.72(m,1H),2.42-2.61(m,6H). 13 CNMR(100MHz,CD 3 CN)δ152.28,149.49,134.12,133.59,129.18,129.07,128.58,127.79,126.83,124.68,123.31,123.13,122.68,119.10,96.71,96.34。
specific example four (preparation and performance of Pt (II) complex Pt 4) the reaction equation is as follows:
at 50℃adding ligand HL 2 PF 6 77.8mg (0.2 mmol), acetone 5mL, silver oxide 23mg (0.1 mmol), reacted for 4 hours, filtered. Adding Pt (COD) Cl into the filtrate 2 74.8mg (0.2 mmol) and the reaction was continued at room temperature for 2 hours, and the filtrate was concentrated to 2mL, and diethyl ether was added to precipitate a yellow solid, which was washed 2 times with diethyl ether. Then acetonitrile is used for dissolution, diethyl ether is slowly added, and recrystallization is carried out to obtain 83mg of benzothiazole functionalized nitrogen heterocyclic carbene ligand coordinated platinum compound Pt4, and the yield is 56%. The diethyl ether volatilization method is used for obtaining the crystal of the Pt4 compound, and the single crystal structure is shown in figure 4.
The physical and chemical properties of the Pt4 complex are as follows: pale yellow crystals, which are easily dissolved in solvents such as acetonitrile, DMSO, DMF, etc., and whose nuclear magnetic resonance data are shown in fig. 11 and 12, are: 1 HNMR(400MHz,DMSO)δ8.48(s,1H),8.31(d,J＝8.0,1H),8.20(s,1H),8.12(d,J＝8.0,1H),7.66(t,J＝8.0,8.0,1H),7.59(t,J＝8.0,8.0,1H),6.34-6.29(m,1H),6.10-6.04(m,1H),5.23-5.14(m,2H),4.97-4.92(m,1H),2.91-2.81(m,1H),2.78-2.71(m,1H),2.64-2.58(m,3H),2.45-2.30(m,3H),1.63(d,J＝4.0,3H),1.50(d,J＝8.0,3H). 13 CNMR(100MHz,DMSO)δ157.41,150.28,149.45,133.63,128.13,126.96,124.30,123.62,123.27,122.11,118.52,116.92,96.97,95.79,55.69,32.91,31.15,29.54,27.78,23.18,22.14。
specific example five (Pt (II) Complex application in antitumor drug
The benzothiazole functionalized azacyclo-carbene platinum compounds obtained in examples 1-4 demonstrate the anticancer bioactivity of the azacyclo-carbene platinum compounds of the present application by in vitro cytotoxicity experiments:
cancer cells (Hela), human colon cancer (HCT 116 and HT-29), human ovarian clear cell carcinoma (ES-2) and liver cancer (7402)) in the growing period are taken, after pancreatin digestion, the plates (96-well plates, 5×103 cells/well) are incubated at 37 ℃ for 24 hours to adhere the cells, benzothiazole-functionalized N-heterocyclic carbene platinum compounds and cis-platinum cis-Pt (100 μl/well) prepared in examples 1-4 with different concentrations are added, after 48 hours of culture, 30 μl of thiazole blue (MTT, 5 mg/mL) is added to each well, after 4 hours of continuous culture, the supernatant is removed, 100 μl of dimethyl sulfoxide (DMSO) is added to each well, shaking is carried out to fully dissolve the crystallization products, the absorbance of each well is detected at 492nm on an enzyme-labeled instrument, a cell survival curve is drawn, as shown in FIGS. 13 to 17, and the half-inhibition concentration (IC 50) value of each group of nanoparticles on the cells is calculated. The in vitro toxicity results of the antitumor drug liposome on various tumor cells are shown in table 1.
Table 1: benzothiazole functionalized Azacyclo-carbene platinum Compounds and cisplatin to cancer cells IC50 (. Mu.M) in examples 1-4
The Pt (II) complex with anti-tumor activity is used for preparing medicines for treating cervical cancer (Hela), human colon cancer (HCT 116 and HT-29), human ovarian clear cell carcinoma (ES-2) and liver cancer (7402). Compared with cisplatin, the Pt (II) complex prepared by the application has higher anti-tumor activity in four cancer cells, and can effectively inhibit the division and proliferation of the cancer cells.
In the description of the present specification, a description referring to terms "one embodiment," "some embodiments," "examples," "specific examples," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present application. In this specification, schematic representations of the above terms are not necessarily directed to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Further, one skilled in the art can engage and combine the different embodiments or examples described in this specification.
While embodiments of the present application have been shown and described, it will be understood by those of ordinary skill in the art that: many changes, modifications, substitutions and variations may be made to the embodiments without departing from the spirit and principles of the application, the scope of which is defined by the claims and their equivalents.
Claims (10)
1. A Pt (II) complex having antitumor activity, characterized in that: the Pt (II) complex takes benzothiazole functionalized N-heterocyclic carbene compound as a ligand, a central platinum atom is of a four-coordination structure, and an anion of the Pt (II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halogen ion, wherein the cationic structural formula is as follows:
2. a crystal of Pt (II) complex having antitumor activity according to claim 1, wherein the crystal belongs to the triclinic system, the P-1 space group, and the unit cell parameters are: a= 7.5537 (3),α＝81.854(5)°,β＝88.595(4)°,γ＝69.934(5)°,/>
3. a Pt (II) complex having antitumor activity, characterized in that: the Pt (II) complex takes benzothiazole functionalized N-heterocyclic carbene compound as a ligand, a central platinum atom is of a four-coordination structure, and an anion of the Pt (II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halogen ion, wherein the cationic structural formula is as follows:
4. a crystal of Pt (II) complex having antitumor activity as claimed in claim 3, wherein the crystal belongs to the triclinic system, the P-1 space group, and the unit cell parameters are: α＝82.225(3)°,β＝71.358(4)°,γ＝64.223(4)°,/>
5. a Pt (II) complex having antitumor activity, characterized in that: the Pt (II) complex takes benzothiazole functionalized N-heterocyclic carbene compound as a ligand, a central platinum atom is of a four-coordination structure, and an anion of the Pt (II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halogen ion, wherein the cationic structural formula is as follows:
6. the crystal of Pt (II) complex having antitumor activity according to claim 5, wherein the crystal belongs to orthorhombic system, P-1 space group, and the unit cell parameters are: α＝90°,β＝90°,γ＝90°,/>
7. a Pt (II) complex having antitumor activity, characterized in that: the Pt (II) complex takes benzothiazole functionalized N-heterocyclic carbene compound as a ligand, a central platinum atom is of a four-coordination structure, and an anion of the Pt (II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halogen ion, wherein the cationic structural formula is as follows:
8. the crystal of Pt (II) complex having antitumor activity as claimed in claim 7, wherein the crystal belongs to the triclinic system, P-1 space group, and the unit cell parameters are: α＝89.725(5)°,β＝88.266(5)°,γ＝87.877(5)°,/>
9. the method for preparing a Pt (II) complex having antitumor activity as claimed in claim 1, comprising the steps of:
in acetonitrile which is an organic solvent, the molar ratio is 2:1 and silver oxide, reacting at 50 ℃ in the dark for 4-6 hours, filtering, adding Pt (COD) Cl into the filtrate 2 The molar ratio of the benzothiazole functionalized imidazole salt ligand to the benzothiazole functionalized imidazole salt ligand is 1:1, continuing to react for 2-4 hours at room temperature, filtering, and obtaining light yellow blocky crystals which are Pt (II) complexes through an diethyl ether volatilization method.
10. The use of a Pt (II) complex having anti-tumor activity according to any one of claims 1, 3, 5, 7 for the preparation of an anti-tumor medicament, in the following manner: taking cancer cells in a growing period, digesting the cancer cells by pancreatin, incubating the plates for 24 hours at 37 ℃ to enable the cells to adhere to the walls, and adding the prepared benzothiazole functionalized azacyclo-carbene platinum compound and cisplatin cis-Pt100 mu L/hole, wherein the benzothiazole functionalized azacyclo-carbene platinum compound is selected from the following structures:
after 48h of incubation, 30. Mu.L of thiazole blue was added to each well, the supernatant was removed after further incubation for 4h, and 100. Mu.L of dimethyl was added to each wellAnd (3) the base sulfoxide is oscillated to fully dissolve the crystallization product, wherein the cancer cells in the growing period are selected from cervical cancer, colon cancer, ovarian clear cell carcinoma or liver cancer.
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