CN114315913B - A Pt(II) complex with anti-tumor activity and its preparation method and application - Google Patents

Abstract

The invention discloses a Pt(II) complex with anti-tumor activity, which includes: the Pt(II) complex uses a benzothiazole-functionalized nitrogen heterocyclic carbene compound as a ligand, and the central platinum atom is a tetraligand. bit structure, one of the cationic structural formulas is: The invention also discloses a preparation method of a Pt(II) complex with anti-tumor activity, and a drug for treating cervical cancer, human colon cancer, human ovarian clear cell cancer and liver cancer using the Pt(II) complex with anti-tumor activity. uses in. The complex of the invention has a changeable structure, convenient synthesis, stable performance, environmental friendliness, and can exist stably in the air for a long time. This type of Pt(II) compound has a strong inhibitory effect on the growth of tumor cells and can be used as a drug for tumor treatment.

Description

A Pt(II) complex with anti-tumor activity and its preparation method and application

Technical field

The present invention relates to the field of biomedicine technology, and more specifically, the present invention relates to Pt(II) complexes with anti-tumor activity and their preparation methods and applications.

Background technique

Cancer is one of the main causes of human death, and the research and development of anti-tumor drugs has always been a major global issue facing mankind. In 1965, Rosenberg et al. first reported cisplatin (cis-[Pt(NH3) ₂ Cl ₂ ]) with anticancer activity, thus creating a new field of pharmaceutical inorganic chemistry. Cisplatin is a legendary veteran in the field of anti-cancer drugs. Since its FDA approval in 1978 for the treatment of prostate cancer and lymphoma, cisplatin has been widely used clinically for more than 40 years. Cisplatin is also used to treat various tumors such as lung cancer, cervical cancer, ovarian cancer, etc. It is estimated that at least 50% of cancer patients have received platinum anti-cancer drugs. The discovery and application of cisplatin is a milestone in the development of tumor chemotherapy, and it is known as the "penicillin in the field of anti-tumor drugs".

Cisplatin has achieved great success in treating cancer, but it has poor water solubility, low oral activity, and strong toxic and side effects. For example, large doses or continuous use can lead to nephrotoxicity, ototoxicity, and neurotoxicity. In order to overcome the clinical shortcomings of cisplatin, reduce toxicity and improve drug resistance, a series of platinum compounds have been studied. The resistance mechanism of cisplatin is complex and has not yet been fully elucidated. If the DNA damage caused by cisplatin is discovered by the DNA repair mechanism and activates the DNA repair pathway, or the DNA damage is completely repaired, cisplatin will lose its efficacy. This is one of the important mechanisms by which cells develop cisplatin resistance. Therefore, research and development of new platinum drugs to improve cisplatin resistance has attracted widespread attention from researchers.

Anti-tumor drugs based on metal complexes, mainly platinum complexes, copper complexes and ruthenium complexes, have made breakthroughs in design routes and synthesis methods. The present invention uses benzothiazole functionalized N-heterocyclic carbene (NHC) as a ligand to synthesize Pt(II) compounds and study their anti-tumor activity, in order to screen out high-efficiency, low-toxic anti-tumor drugs.

Contents of the invention

The purpose of the present invention is to provide a Pt(II) complex with anti-tumor activity and its preparation method and application, so as to solve the problems raised in the above background technology.

In order to achieve the above object, the present invention provides the following technical solution: a Pt(II) complex with anti-tumor activity, the Pt(II) complex uses a benzothiazole-functionalized nitrogen heterocyclic carbene compound as a ligand, and the central platinum The atoms have a four-coordinate structure, and the anion of the Pt(II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halide ion, and the cation structural formula is:

Furthermore, the Pt1 compound belongs to the triclinic crystal system, 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)°,/>

A Pt(II) complex with anti-tumor activity. The Pt(II) complex uses a benzothiazole-functionalized nitrogen heterocyclic carbene compound as a ligand, and the central platinum atom has a four-coordination structure. The Pt(II) complex ) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halide ion, and the cation structural formula is:

Furthermore, the Pt2 compound belongs to the triclinic crystal system, P-1 space group, and the unit cell parameters are: α＝82.225(3)°, β＝71.358(4)°, γ＝64.223(4)°,/>

A Pt(II) complex with anti-tumor activity. The Pt(II) complex uses a benzothiazole-functionalized nitrogen heterocyclic carbene compound as a ligand, and the central platinum atom has a four-coordination structure. The Pt(II) complex ) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halide ion, and the cation structural formula is:

Furthermore, the Pt3 compound belongs to the orthorhombic crystal system, P-1 space group, and the unit cell parameters are: α＝90°, β＝90°, γ＝90°,/>

A Pt(II) complex with anti-tumor activity. The Pt(II) complex uses a benzothiazole-functionalized nitrogen heterocyclic carbene compound as a ligand, and the central platinum atom has a four-coordination structure. The Pt(II) complex ) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halide ion, and the cation structural formula is:

Furthermore, the Pt4 compound belongs to the triclinic crystal system, P-1 space group, and the unit cell parameters are: α＝89.725(5)°, β＝88.266(5)°, γ＝87.877(5)°,/>

A method for preparing a Pt(II) complex with anti-tumor activity, including the following steps:

In the organic solvent acetonitrile or acetone, add benzothiazole functionalized imidazole salt ligand and silver oxide with a molar ratio of 2:1, react for 4-6 hours at 50°C in the dark, filter, and add Pt(COD) to the filtrate )Cl ₂ , the molar ratio of it to the benzothiazole functionalized imidazole salt ligand is 1:1, continue the reaction at room temperature for 2-4 hours, filter, and obtain light yellow block crystals through the diethyl ether evaporation method, which is Pt(II) complex things.

The application of Pt(II) complexes Pt1, Pt2, Pt3 and Pt4 with anti-tumor activity in the preparation of anti-tumor drugs. The specific application method is as follows: take the cancer cells in the growth phase, digest them with trypsin, seed the plate, and incubate at 37°C for 24 hours. Make the cells adhere to the wall, add different concentrations of the benzothiazole-functionalized nitrogen heterocyclic carbene platinum compound prepared in Examples 1-4 and cisplatin cis-Pt (100 μL/well). After culturing for 48 hours, add 30 μL of thiazole to each well. Blue (MTT, 5 mg/mL), continue culturing for 4 hours, remove the supernatant, add 100 μL dimethyl sulfoxide (DMSO) to each well, and shake to fully dissolve the crystallized product.

Compared with existing technology, it has the following beneficial effects:

The compound prepared by the invention has variable structure, convenient synthesis, stable performance, environmental friendliness, and can exist stably in the air for a long time.

The compound prepared by the invention has a strong inhibitory effect on the growth of tumor cells and can be used as a drug for tumor treatment.

Description of drawings

Figure 1 is a single crystal structure diagram of the Pt(II) complex Pt1 cation;

Figure 2 is a single crystal structure diagram of the Pt(II) complex Pt2 cation;

Figure 3 is a single crystal structure diagram of Pt(II) complex Pt3 cation;

Figure 4 is a single crystal structure diagram of the Pt(II) complex Pt4 cation;

Figure 5 is the ¹ HNMR spectrum of Pt(II) complex Pt1;

Figure 6 is the ¹³ CNMR spectrum of Pt(II) complex Pt1;

Figure 7 is the ¹ HNMR spectrum of Pt(II) complex Pt2;

Figure 8 is the ¹³ CNMR spectrum of Pt(II) complex Pt2;

Figure 9 is the ¹ HNMR spectrum of Pt(II) complex Pt3;

Figure 10 is the ¹³ CNMR spectrum of Pt(II) complex Pt3;

Figure 11 is the ¹ HNMR spectrum of Pt(II) complex Pt4;

Figure 12 is the ¹³ CNMR spectrum of Pt(II) complex Pt4;

Figure 13 is a cell survival curve of Pt(II) complex against cervical cancer Hela;

Figure 14 is a cell survival curve of Pt(II) complex against human colon cancer HCT116;

Figure 15 is a cell survival curve of Pt(II) complex against human colon cancer HT-29;

Figure 16 is a cell survival curve of Pt(II) complex against human ovarian clear cell carcinoma ES-2;

Figure 17 is a cell survival curve of Pt(II) complex against liver cancer 7402.

Detailed ways

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only some of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts fall within the scope of protection of the present invention.

Please refer to Figure 1-17, a Pt(II) complex with anti-tumor activity. The Pt(II) complex uses a benzothiazole-functionalized nitrogen heterocyclic carbene compound as a ligand, and the central platinum atom is four-coordinated. Structure, the anion of the Pt(II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halide ion, wherein the cation structural formula is:

A Pt(II) complex with anti-tumor activity. The Pt1 compound belongs to the triclinic crystal system, P-1 space group, and the unit cell parameter is: a=7.5537(3), α＝81.854(5)°, β＝88.595(4)°, γ＝69.934(5)°,/>

A Pt(II) complex with anti-tumor activity. The Pt(II) complex uses a benzothiazole-functionalized nitrogen heterocyclic carbene compound as a ligand, and the central platinum atom has a four-coordination structure. The Pt(II) complex ) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halide ion, and the cation structural formula is:

A Pt(II) complex with anti-tumor activity. The Pt2 compound belongs to the triclinic crystal system and P-1 space group. The unit cell parameters are: α＝82.225(3)°, β＝71.358(4)°, γ＝64.223(4)°,/>

A Pt(II) complex with anti-tumor activity. The Pt(II) complex uses a benzothiazole-functionalized nitrogen heterocyclic carbene compound as a ligand, and the central platinum atom has a four-coordination structure. The Pt (II) The anion of the complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halide ion, and the cation structural formula is:

A Pt(II) complex with anti-tumor activity. The Pt3 compound belongs to the orthorhombic crystal system, P-1 space group, and the unit cell parameters are: α＝90°, β＝90°, γ＝90°,/>

A Pt(II) complex with anti-tumor activity. The Pt(II) complex uses a benzothiazole-functionalized nitrogen heterocyclic carbene compound as a ligand, and the central platinum atom has a four-coordination structure. The Pt(II) complex ) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halide ion, and the cation structural formula is:

A Pt(II) complex with anti-tumor activity. The Pt4 compound belongs to the triclinic crystal system and P-1 space group. The unit cell parameters are: α＝89.725(5)°, β＝88.266(5)°, γ＝87.877(5)°,/>

A method for preparing a Pt(II) complex with anti-tumor activity, including the following steps:

In the organic solvent acetonitrile or acetone, add benzothiazole functionalized imidazole salt ligand and silver oxide with a molar ratio of 2:1, react for 4-6 hours at 50°C in the dark, filter, and add Pt(COD) to the filtrate )Cl ₂ , the molar ratio of it to the benzothiazole functionalized imidazole salt ligand is 1:1, continue the reaction at room temperature for 2-4 hours, filter, and obtain light yellow block crystals through the diethyl ether evaporation method, which is Pt(II) complex things.

The application of Pt(II) complexes Pt1, Pt2, Pt3 and Pt4 with anti-tumor activity in the preparation of anti-tumor drugs. The specific application method is as follows: take the cancer cells in the growth phase, digest them with trypsin, seed the plate, and incubate at 37°C for 24 hours. Make the cells adhere to the wall, add different concentrations of the benzothiazole-functionalized nitrogen heterocyclic carbene platinum compound prepared in Examples 1-4 and cisplatin cis-Pt (100 μL/well). After culturing for 48 hours, add 30 μL of thiazole to each well. Blue (MTT, 5 mg/mL), continue culturing for 4 hours, remove the supernatant, add 100 μL dimethyl sulfoxide (DMSO) to each well, and shake to fully dissolve the crystallized product.

The nitrogen heterocyclic carbene platinum compound of the present application has a changeable structure, convenient synthesis, stable performance, environmental friendliness, and can exist stably in the air for a long time. The crystals prepared in the following Examples 1 to 4 can be placed in the air without deterioration. It has broad application prospects in the pharmaceutical and fine chemical industries.

Specific Example 1: (Preparation and properties of Pt(II) complex Pt1), the reaction equation is as follows:

At 50°C, add ligand HL ¹ PF ₆ 87.4 mg (0.2 mmol), acetonitrile 5 mL, and silver oxide 23 mg (0.1 mmol), react for 4 hours, and filter. Add Pt(COD)Cl ₂ 74.8mg (0.2mmol) to the filtrate, continue the reaction at room temperature for 2 hours, centrifuge and filter, concentrate the filtrate to 2mL, add diethyl ether to precipitate a yellow solid, wash the yellow solid twice with diethyl ether, and then dissolve it with acetonitrile. Slowly add diethyl ether and recrystallize to obtain 73 mg of platinum compound Pt1 coordinated by benzothiazole functionalized nitrogen heterocyclic carbene ligand, with a yield of 48%. The crystal of Pt1 compound was obtained by the diethyl ether evaporation method. The single crystal structure is shown in Figure 1.

The physical and chemical properties of Pt1 compound are: light yellow crystal, easily soluble in acetonitrile, DMSO, DMF, etc. Its nuclear magnetic resonance data is shown in Figure 5 and Figure 6, which is: 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 Example 2: (Preparation and properties of Pt(II) complex Pt2), the reaction equation is as follows:

At 50°C, add ligand HL ¹ PF ₆ 87.4 mg (0.2 mmol), acetonitrile 5 mL, and silver oxide 23 mg (0.1 mmol), react for 4 hours, and filter. Add 74.8 mg of Pt(COD)Cl ₂ (0.2 mmol) and 18 mg of acetic acid (0.3 mmol) to the filtrate. Continue the reaction at 50°C for 2 hours. Centrifuge and filter. The filtrate is concentrated to 2 mL. Add diethyl ether to precipitate a yellow solid. Wash the yellow solid with diethyl ether. Dissolve it twice with acetonitrile, slowly add diethyl ether, and recrystallize to obtain 53 mg of benzothiazole-functionalized nitrogen heterocyclic carbene ligand-coordinated platinum compound Pt2, with a yield of 39%. The crystal of Pt2 compound was obtained by the diethyl ether evaporation method, and the single crystal structure is shown in Figure 2.

The physical and chemical properties of Pt2 compound are: light yellow crystal, easily soluble in acetonitrile, DMSO, DMF and other solvents. Its nuclear magnetic resonance data is shown in Figure 7 and Figure 8, which is: 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.

Specific Example 3: (Preparation and properties of Pt(II) complex Pt3), the reaction equation is as follows:

At 50°C, add ligand HL ¹ PF ₆ 87.4 mg (0.2 mmol), acetone 5 mL, and silver oxide 23 mg (0.1 mmol), react for 4 hours, and filter. Add 74.8 mg (0.2 mmol) of Pt(COD)Cl ₂ to the filtrate, continue the reaction at room temperature for 2 hours, centrifuge and filter, concentrate the filtrate to 2 mL, add diethyl ether to precipitate a yellow solid, and wash the yellow solid twice with diethyl ether. Then dissolve with acetonitrile, slowly add diethyl ether, and recrystallize to obtain 96 mg of platinum compound Pt3 coordinated by benzothiazole functionalized nitrogen heterocyclic carbene ligand, with a yield of 61%. The crystal of Pt3 compound was obtained by the diethyl ether evaporation method, and the single crystal structure is shown in Figure 3.

The physical and chemical properties of Pt3 compound are: light yellow crystal, easily soluble in acetonitrile, DMSO, DMF and other solvents. Its nuclear magnetic resonance data is shown in Figure 9 and Figure 10, which is: 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 4 (Preparation and Properties of Pt(II) Complex Pt4), the reaction equation is as follows:

At 50°C, add ligand HL ² PF ₆ 77.8 mg (0.2 mmol), acetone 5 mL, and silver oxide 23 mg (0.1 mmol), react for 4 hours, and filter. Add 74.8 mg (0.2 mmol) of Pt(COD)Cl ₂ to the filtrate, continue the reaction at room temperature for 2 hours, centrifuge and filter, concentrate the filtrate to 2 mL, add diethyl ether to precipitate a yellow solid, and wash the yellow solid twice with diethyl ether. Then dissolve with acetonitrile, slowly add diethyl ether, and recrystallize to obtain 83 mg of platinum compound Pt4 coordinated by benzothiazole functionalized nitrogen heterocyclic carbene ligand, with a yield of 56%. The crystal of Pt4 compound was obtained by the diethyl ether evaporation method, and the single crystal structure is shown in Figure 4.

The physical and chemical properties of Pt4 complex are: light yellow crystal, easily soluble in acetonitrile, DMSO, DMF and other solvents. Its nuclear magnetic resonance data is shown in Figure 11 and Figure 12, which is: 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 5 (Application of Pt(II) complexes in anti-tumor drugs)

The benzothiazole-functionalized nitrogen-heterocyclic carbene platinum compound obtained in Examples 1-4 was used to elucidate the anti-cancer biological activity of the nitrogen-heterocyclic carbene platinum compound of the present invention through in vitro cytotoxicity experiments:

Cancer cells in the growth phase (cervical cancer (Hela), human colon cancer (HCT116 and HT-29), human ovarian clear cell carcinoma (ES-2) and liver cancer (7402)) were taken, digested with trypsin, and seeded on a 96-well plate plate, 5×103 cells/well), incubate at 37°C for 24 hours to allow the cells to adhere, and add different concentrations of the benzothiazole-functionalized nitrogen heterocyclic carbene platinum compound and cisplatin cis-Pt prepared in Examples 1-4. (100 μL/well), after 48 hours of culture, add 30 μL thiazole blue (MTT, 5 mg/mL) to each well, continue to culture for 4 hours, remove the supernatant, add 100 μL dimethyl sulfoxide (DMSO) to each well, and shake to crystallize the product. Fully dissolve, measure the absorbance of each well at 492nm on a microplate reader, draw a cell survival curve, as shown in Figures 13 to 17, and calculate the half inhibitory concentration (IC50) value of each group of nanoparticles on cells. The in vitro toxicity results of anti-tumor drug liposomes on various tumor cells are shown in Table 1.

Table 1: IC50 (μM) of benzothiazole-functionalized nitrogen heterocyclic carbene platinum compounds and cisplatin on cancer cells in Examples 1-4

The above-mentioned Pt(II) complexes with anti-tumor activity are used in the treatment of cervical cancer (Hela), human colon cancer (HCT116 and HT-29), human ovarian clear cell carcinoma (ES-2) and liver cancer (7402). the use of. In vitro tumor cell growth inhibition experiments have confirmed that compared with cisplatin, the Pt(II) complex prepared by the present invention exhibits higher anti-tumor activity in four types of cancer cells and can effectively inhibit the division and proliferation of cancer cells. .

In the description of this specification, reference to the terms "one embodiment," "some embodiments," "an example," "specific examples," or "some examples" or the like means that specific features are described in connection with the embodiment or example. , structures, materials or features are included in at least one embodiment or example of the invention. In this specification, the schematic expressions of the above terms are not necessarily directed to the same embodiment or example. Furthermore, the specific features, structures, materials or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, those skilled in the art may join and combine the different embodiments or examples described in this specification.

Although the embodiments of the present invention have been shown and described, those of ordinary skill in the art will appreciate that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and purposes of the invention. The scope of the invention is defined by the claims and their equivalents.

Claims (10)

1. A Pt(II) complex with anti-tumor activity, characterized in that: the Pt(II) complex uses a benzothiazole-functionalized nitrogen heterocyclic carbene compound as a ligand, and the central platinum atom has a four-coordinate structure , the anion of the Pt(II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halide ion, wherein the cation structural formula is: 2. The crystal of a Pt(II) complex with anti-tumor activity as claimed in claim 1, characterized in that the crystal belongs to the triclinic system, 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 with anti-tumor activity, characterized in that: the Pt(II) complex uses a benzothiazole-functionalized nitrogen heterocyclic carbene compound as a ligand, and the central platinum atom has a four-coordination structure. , the anion of the Pt(II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halide ion, wherein the cation structural formula is: 4. The crystal of a Pt(II) complex with anti-tumor activity as claimed in claim 3, characterized in that the crystal belongs to the triclinic system, 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 with anti-tumor activity, characterized in that: the Pt(II) complex uses a benzothiazole-functionalized nitrogen heterocyclic carbene compound as a ligand, and the central platinum atom has a four-coordination structure. , the anion of the Pt(II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halide ion, wherein the cation structural formula is: 6. The crystal of a Pt(II) complex with anti-tumor activity as claimed in claim 5, characterized in that the crystal belongs to the orthorhombic crystal system, P-1 space group, and the unit cell parameters are: α＝90°, β＝90°, γ＝90°,/> 7. A Pt(II) complex with anti-tumor activity, characterized in that: the Pt(II) complex uses a benzothiazole-functionalized nitrogen heterocyclic carbene compound as a ligand, and the central platinum atom has a four-coordination structure. , the anion of the Pt(II) complex is one of hexafluorophosphate ion, tetrafluoroborate ion or halide ion, wherein the cation structural formula is: 8. The crystal of a Pt(II) complex with anti-tumor activity as claimed in claim 7, characterized in that 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 preparation method of Pt(II) complex with anti-tumor activity as claimed in claim 1, characterized in that it includes the following steps: In the organic solvent acetonitrile, add benzothiazole functionalized imidazole salt ligand and silver oxide with a molar ratio of 2:1, react for 4-6 hours at 50°C in the dark, filter, and add Pt(COD)Cl to the filtrate. ₂ , the molar ratio between it and the benzothiazole functionalized imidazole salt ligand is 1:1, continue the reaction at room temperature for 2-4 hours, filter, and obtain light yellow block crystals through the diethyl ether evaporation method, which is the Pt(II) complex. 10. The application of the Pt(II) complex with anti-tumor activity in the preparation of anti-tumor drugs as claimed in any one of claims 1, 3, 5 and 7, characterized in that the specific application method is as follows: take the growth phase Cancer cells were digested with trypsin, seeded on a plate, and incubated at 37°C for 24 hours to allow the cells to adhere. Add the prepared benzothiazole-functionalized nitrogen heterocyclic carbene platinum compound and cisplatin cis-Pt 100 μL/well. The benzothiazole-functionalized The nitrogen heterocyclic carbene platinum compound is selected from the following structure: After culturing for 48 hours, add 30 μL of thiazole blue to each well. After continuing to culture for 4 hours, remove the supernatant. Add 100 μL of dimethyl sulfoxide to each well and shake to fully dissolve the crystallized product. The growth phase cancer cells are selected from cervical cancer and colon cancer. , ovarian clear cell carcinoma or liver cancer.