A tetranuclear nodal Zn(II) complex with antitumor activity, its preparation method and application

Abstract

The present invention discloses a tetranuclear nodular Zn(II) complex with antitumor activity, its preparation method and application, belonging to the field of pharmaceutical technology. The molecular formula of the tetranuclear nodular Zn(II) complex with antitumor activity is [Zn4 II (C 16 H 12 Br2N8-H)4](ClO4)4·8CH3OH·5H2O, and the ligand is 4,6-bis(6-bromopyridine-2-carbaldehyde)pyrimidine hydrazone. The complex of the present invention has significant inhibitory effects on the proliferation of human breast cancer cells MCF-7 and lung cancer cells A549, and the inhibitory activity is significantly stronger than that of the positive control drug cisplatin, and it has no cytotoxicity to normal cells HL-7702. The inhibitory effect of the complex of the present invention on tumor cells is also stronger than that of using the ligand alone. It shows that the tetranuclear nodular Zn(II) complex with antitumor activity of the present invention has good in vitro antitumor activity and is expected to be developed into an antitumor drug.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and particularly relates to a tetranuclear nodal Zn(II) complex with antitumor activity, a preparation method thereof, and an application thereof. Background Art

[0002] Tumor is a disease that seriously endangers human life and health. At present, chemotherapy is one of the most effective methods for treating various tumors. However, existing chemotherapy drugs generally have limitations such as poor selectivity, strong drug resistance, and serious toxic and side effects, which seriously affect the quality of life of patients after surgery. Therefore, designing and synthesizing antitumor drugs with high efficiency, high selectivity, and low side effects is an important direction in the research of the medical and chemical fields. The discovery of cisplatin has opened up a new field for the research of metal complex antitumor drugs. The successful application of platinum-based antitumor drugs in clinical practice has greatly interested people in the development of metal complex anticancer drugs. Pharmacological studies have shown that after metal ions coordinate with biologically active organic ligands, a dual-effect synergistic effect can be formed, thereby significantly improving their antitumor activity. Research has shown that compared with mononuclear and binuclear complexes, polynuclear homo- and heterometallic complexes often have more significant biological activities. At present, the research on antitumor complexes mainly focuses on mononuclear and binuclear complexes, and there are few reports on polynuclear complexes. There is no literature report on the research of the antitumor activity of tetranuclear Zn(II) complexes.

[0003] Zinc, as an essential trace element in the human body, participates in the synthesis and activity of many enzymes such as carbonic anhydrase, DNA polymerase, and RNA polymerase in the body, is crucial for the division process of many cells, and is an important regulatory ion in cell metabolism. Therefore, by synthesizing a tetranuclear Zn(II) complex with a pyrimidine ring, the present invention is expected to find an antitumor drug with high efficiency, low toxicity, and small side effects by using the dual-effect synergistic effect of the ligand and the metal. Summary of the Invention

[0004] In view of the problems existing in the above-mentioned prior art, the present invention provides a tetranuclear nodal Zn(II) complex with antitumor activity, a preparation method thereof, and an application thereof. The structure of the complex is novel and has significant antitumor activity.

[0005] To achieve the above object, the present invention provides the following technical solutions:

[0006] Technical solution 1: A tetranuclear nodal Zn(II) complex with antitumor activity, the molecular formula of the tetranuclear nodal Zn(II) complex is [Zn4 II (C 16 H 12 Br2N8-H)4](ClO4)4·8CH3OH·5H2O, and the main structure of the complex is as Figure 4 shown;

[0007] The ligand of the tetranuclear node-like Zn(II) complex is 4,6-bis(6-bromopyridine-2-carbaldehyde)pyrimidine hydrazone, with the molecular formula C 16 H 12 Br2N8, and the structural formula is shown in Formula (Ⅰ):

[0008]

[0009] Furthermore, the tetranuclear node-like Zn(II) complex is in the tetragonal crystal system, space group P4(2) / nmc, and the unit cell parameters are as follows: α = 90°, β = 90°, γ = 90°,

[0010] Furthermore, the preparation method of the ligand 4,6-bis(6-bromopyridine-2-carbaldehyde)pyrimidine hydrazone includes the following steps:

[0011] (1) Disperse 15 mmol of 4,6-dichloropyrimidine in 15 mL of hydrazine hydrate, stir and react at room temperature for 1 h, then slowly heat the mixture to 60 °C and continue the reaction, and white solid gradually precipitates to obtain the crude product of 4,6-dihydrazinopyrimidine intermediate;

[0012] (2) Wash the crude intermediate product with a mixed solvent of ethanol and water multiple times to obtain the 4,6-dihydrazinopyrimidine intermediate. The volume ratio of ethanol to water is 1:1, and the concentration of ethanol is 99.7%; the number of washing times is 3;

[0013] (3) Dissolve 2 mmol of 4,6-dihydrazinopyrimidine intermediate and 4.2 mmol of 6-bromopyridine-2-carbaldehyde in absolute ethanol respectively, mix them and stir at room temperature for 2 h, and carry out an oil bath reflux reaction. White solid gradually precipitates during the reaction;

[0014] (4) After the reflux reaction is completed, carry out suction filtration, wash with ethanol multiple times, and purify by column chromatography to obtain the product ligand 4,6-bis(6-bromopyridine-2-carbaldehyde)pyrimidine hydrazone.

[0015] Technical solution two: A preparation method of the tetranuclear node-like Zn(II) complex with antitumor activity as described above, including the following steps:

[0016] 1) Dissolve the ligand 4,6-bis(6-bromopyridine-2-carbaldehyde)pyrimidine hydrazone in a mixed solvent of methanol and acetonitrile to obtain a ligand solution;

[0017] 2) Add zinc perchlorate hexahydrate to the ligand solution and stir evenly;

[0018] 3) Filtration. The obtained filtrate was allowed to evaporate naturally at room temperature until red block crystals precipitated, which were the tetra-nuclear nodular Zn(II) complex.

[0019] Furthermore, the volume ratio of methanol to acetonitrile was 2:1; the molar ratio of 4,6-bis(6-bromopyridine-2-carboxaldehyde)pyrimidine hydrazone to zinc perchlorate hexahydrate was 1:1.2.

[0020] Technical solution three: Application of the described tetra-nuclear nodular Zn(II) complex with anti-tumor activity in the preparation of anti-tumor drugs.

[0021] Furthermore, the tumor cells in the anti-tumor drugs include human breast cancer cells MCF-7, lung cancer cells A549, or normal liver cells HL-7702.

[0022] Compared with the prior art, the present invention has the following advantages and technical effects:

[0023] 1. The ligand 4,6-bis(6-bromopyridine-2-carboxaldehyde)pyrimidine hydrazone of the present invention is significantly different in structure from the reported heterocyclic pyrimidine-based anti-tumor derivatives. The present invention is based on pyrimidine-pyridine bis-hydrazone derivatives, and there is no literature report on the anti-tumor activity research of such derivatives and their functional complexes. The ligand synthesis method is simple, the operation is convenient, the yield is relatively high, and it is easy to industrialize.

[0024] 2. The ligand 4,6-bis(6-bromopyridine-2-carboxaldehyde)pyrimidine hydrazone of the present invention belongs to a chelating ligand. Each Zn(II) atom adopts a six-coordination mode, and chelates and coordinates with the N atoms on the pyrimidine ring, the N atoms on the C=N double bond, and the N atoms on the pyridine ring from 2 pyrimidine hydrazone ligands respectively. 4 ligands and 4 Zn(II) centers coordinate to form a tetra-nuclear nodular structure.

[0025] 3. The present invention uses 4,6-bis(6-bromopyridine-2-carboxaldehyde)pyrimidine hydrazone as the ligand and Zn(II) as the central metal, with a feeding ratio of 1:1.2, to prepare the tetra-nuclear nodular Zn(II) complex, effectively solving the problem of the combination of pyrimidine-pyridine bis-hydrazone as the ligand with the transition metal Zn(II).

[0026] 4. Compared with the prior art, the present invention provides a novel synthetic method of a Zn(II) complex with 4,6-bis(6-bromopyridine-2-carboxaldehyde)pyrimidine hydrazone as the ligand, and uses the MTT method to study the inhibitory effects of the 4,6-bis(6-bromopyridine-2-carboxaldehyde)pyrimidine hydrazone ligand and its corresponding Zn(II) complex on the proliferation of tumor cell lines such as human breast cancer cells MCF-7 and lung cancer cells A549, and evaluates the cytotoxicity to normal liver cells HL-7702. The experimental results show that the complex has significant inhibitory effects on the proliferation of the selected tumor cells, IC50 The values were 2.83 μM and 3.83 μM respectively, and the inhibitory activity was significantly stronger than that of the positive control drug Cisplatin, and it had no cytotoxicity to normal cells HL-7702. At the same time, it was found that the inhibitory effect of the tetranuclear nodular Zn(II) complex on tumor cells was also significantly stronger than that of the ligand 4,6-bis(6-bromopyridine-2-carboxaldehyde)pyrimidine hydrazone used alone. This indicates that the tetranuclear nodular Zn(II) complex of the present invention has good in vitro anti-tumor activity and is expected to be developed into an anti-tumor drug.

[0027] 5. The preparation method of the present invention is simple, easy to operate, has mild reaction conditions, high purity, low production cost, is easy to be popularized in industrialization, and has good social and economic benefits. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The drawings constituting a part of this application are used to provide a further understanding of this application. The schematic embodiments of this application and their descriptions are used to explain this application and do not constitute an improper limitation to this application. In the drawings:

[0029] Figure 1 is the 1 HNMR spectrum of the ligand 4,6-bis(6-bromopyridine-2-carboxaldehyde)pyrimidine hydrazone prepared in Example 1 of the present invention;

[0030] Figure 2 is the infrared result diagram of the ligand 4,6-bis(6-bromopyridine-2-carboxaldehyde)pyrimidine hydrazone prepared in Example 1 of the present invention;

[0031] Figure 3 is the infrared result diagram of the tetranuclear nodular Zn(II) complex prepared in Example 2 of the present invention;

[0032] Figure 4 is the main molecular spatial configuration diagram of the tetranuclear nodular Zn(II) complex prepared in Example 2 of the present invention;

[0033] Figure 5 is the main molecular spatial configuration diagram of the pyrimidine-pyridine bis-hydrazone Zn(II) complex prepared in Comparative Example 1;

[0034] Figure 6 is the infrared result diagram of the pyrimidine-pyridine bis-hydrazone Zn(II) complex prepared in Comparative Example 1 of the present invention;

[0035] Figure 7 is the IC 50 histogram of the ligand prepared in Example 1 of the present invention, the tetranuclear nodular Zn(II) complex prepared in Example 2, the comparative complex and the positive control drug Cisplatin acting on two kinds of tumor cells for 48 h. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0036] As used herein, terms such as "comprising", "including", "having", "containing", etc. are all open-ended terms, meaning including but not limited to.

[0037] Unless otherwise specified, the "room temperature" in the present invention is calculated as 25 ± 2 °C.

[0038] All raw materials used in the following examples of the present invention are obtained commercially.

[0039] The following examples are further illustrations of the technical solutions of the present invention.

[0040] Example 1

[0041] The ligand 4,6-bis(6-bromopyridine-2-carbaldehyde)pyrimidine hydrazone has the molecular formula C 16 H 12 Br2N8, and the preparation method is as follows:

[0042] (1) Disperse 15 mmol of 4,6-dichloropyrimidine in 15 mL of 80 wt% hydrazine hydrate, stir and react at room temperature for 1 h, then slowly heat the mixture to 60 °C and continue the reaction, and a white solid gradually precipitates to obtain a crude product of 4,6-dihydrazinopyrimidine intermediate;

[0043] (2) Wash the crude intermediate product 3 times with a mixed solvent of ethanol and water (the volume ratio of ethanol to water is 1:1, and the concentration of ethanol is 99.7%) to obtain the 4,6-dihydrazinopyrimidine intermediate;

[0044] (3) Dissolve 2 mmol of 4,6-dihydrazinopyrimidine intermediate and 4.2 mmol of 6-bromopyridine-2-carbaldehyde in 20 mL of anhydrous ethanol respectively, mix and stir at room temperature for 2 h, and reflux the reaction in an oil bath at 78 °C. During the reaction, a white solid gradually precipitates;

[0045] (4) After the reflux reaction is completed, filter by suction, wash with ethanol multiple times, and purify by column chromatography (the volume ratio of petroleum ether to ethyl acetate = 1:1) to obtain the product ligand 4,6-bis(6-bromopyridine-2-carbaldehyde)pyrimidine hydrazone, with a yield of 84.6% and a purity of 98%.

[0046] The prepared ligand 4,6-bis(6-bromopyridine-2-carbaldehyde)pyrimidine hydrazone 1 HNMR spectrum: 1 HNMR (500 MHz, DMSO-d6) δ (ppm) 11.58 (s, 2H), 8.27 (s, 1H), 8.07 (s, 2H), 7.99 (d, J = 7.5 Hz, 2H), 7.83 (t, J = 7.8 Hz, 2H), 7.62 (d, J = 8.2 Hz, 2H), 6.94 (s, 1H) (as Figure 1as shown).

[0047] The infrared spectrum (cm -1 , KBr) of the prepared 4,6-bis(6-bromopyridine-2-carbaldehyde)pyrimidine hydrazone: 3193, 1582, 1569, 1544, 1454, 1432, 1419, 1394, 1201, 1160, 1137, 1116, 792 (as Figure 2 shown).

[0048] Example 2

[0049] Using the 4,6-bis(6-bromopyridine-2-carbaldehyde)pyrimidine hydrazone prepared in Example 1 as a ligand to prepare a tetra-nuclear nodal Zn(II) complex with anti-tumor activity, the molecular formula is [Zn4 II (C 16 H 12 Br2N8-H)4](ClO4)4·8CH3OH·5H2O, and the preparation method is as follows:

[0050] (1) Dissolve 0.025 mmol of the ligand 4,6-bis(6-bromopyridine-2-carbaldehyde)pyrimidine hydrazone in 10 mL of a mixed solvent (the mixed solvent is composed of methanol and acetonitrile mixed in a volume ratio of 2:1) to obtain a ligand solution;

[0051] (2) Add 0.03 mmol of zinc perchlorate hexahydrate to the ligand solution and stir at room temperature for 2 h;

[0052] (3) Filter, and the obtained filtrate is allowed to evaporate naturally at room temperature. Red block crystals precipitate out after about 10 days, which is the tetra-nuclear nodal Zn(II) complex.

[0053] The infrared spectrum (cm -1 , KBr) of the prepared tetra-nuclear nodal Zn(II) complex: 3070, 1637, 1589, 1538, 1471, 1432, 1398, 1363, 1290, 1228, 1181, 1116, 1016, 624 (as Figure 3 shown).

[0054] The experimental conditions and results of the X-ray single crystal diffraction of the tetra-nuclear nodal Zn(II) complex prepared in this example are as follows:

[0055] The single crystal structure data was determined on a SuperNova Dual diffractometer with a graphite monochromator. A crystal of appropriate size (0.1×0.11×0.12 mm 3 ) was fixed on a glass fiber to collect the crystal data. CuKα radiation was used For the θ and ω scanning modes, 9956 diffraction points were collected in the range of 4.610 < θ < 60.290°, among which the number of independent diffraction points was 3735 (Rint = 0.0628). Empirical absorption correction was carried out using the SADABS program. The molecular structure of the compound was solved by the direct method and refined by full-matrix least-squares method using SHELXTL. All non-hydrogen atoms were refined with anisotropic thermal parameters, and finally the positions of hydrogen atoms were determined by theoretical hydrogenation method.

[0056] The crystal parameters of the prepared single crystal of the tetranuclear nodal Zn(II) complex are shown in Table 1, the important bond length and bond angle data are shown in Table 2, and the main structure of the complex crystal is shown in Figure 4 .

[0057] Table 1 List of crystal parameters of the complex prepared in Example 2

[0058]

[0059]

[0060] Table 2 Main bond length and bond angle data of the complex prepared in Example 2

[0061]

[0062] It can be seen that the complex belongs to the tetragonal system, space group P4(2) / nmc. The Zn atom adopts a six-coordinate mode and is chelated and coordinated with the N atoms on the pyrimidine ring, the N atoms on the C=N double bond, and the N atoms on the pyridine ring from 2 pyrimidine-hydrazone ligands respectively, forming an octahedral configuration. The unit cell parameters are α = 90°, β = 90°, γ = 90°,

[0063] Comparative Example 1

[0064] A pyrimidine-pyridine bis-hydrazone Zn(II) complex, which is 2-phenyl-4,6-bis(pyridine-2-carboxaldehyde)pyrimidine Zn(II) complex, with the molecular formula [Zn4 II (C 22 H 18 N8)4](ClO4)8·7CH3OH·11H2O, as shown (where the numbers 1, 2, 3, 4 represent Zn atoms at different positions), and the main molecular structure is shown in Figure (5).

[0065] Among them, the ligand is 2-phenyl-4,6-bis(pyridine-2-carboxaldehyde)pyrimidine hydrazone, with the molecular formula C 22 H 18 N8, and the structural formula is as shown in Formula (Ⅱ):

[0066]

[0067] 1. The preparation method of the ligand 2-phenyl-4,6-bis(pyridine-2-carboxaldehyde)pyrimidine hydrazone is as follows:

[0068] (1) Dissolve 15 mmol of 2-phenyl-4,6-dichloropyrimidine in 15 mL of 80 wt% hydrazine hydrate, and stir the reaction at room temperature for 1 h to obtain a crude product of the 2-phenyl-4,6-dihydrazinopyrimidine intermediate;

[0069] (2) Wash the crude product of the 2-phenyl-4,6-dihydrazinopyrimidine intermediate three times with a mixed solvent of ethanol and water (the volume ratio of ethanol to water is 1:1, and the concentration of ethanol is 99.7%) to obtain the 2-phenyl-4,6-dihydrazinopyrimidine intermediate;

[0070] (3) Dissolve 2 mmol of the 2-phenyl-4,6-dihydrazinopyrimidine intermediate in 20 mL of absolute ethanol, add 2 mL of pyridine-2-carboxaldehyde, and stir at room temperature for 2 h, then carry out an oil bath reflux reaction;

[0071] (4) After the reflux reaction is completed, filter, wash with ethanol multiple times, and purify by column chromatography (the volume ratio of petroleum ether to ethyl acetate = 1:1) to obtain the product ligand 2-phenyl-4,6-bis(pyridine-2-carboxaldehyde)pyrimidine hydrazone.

[0072] The infrared spectrum (cm -1 , KBr) of the prepared ligand 2-phenyl-4,6-bis(pyridine-2-carboxaldehyde)pyrimidine hydrazone: 3199, 1592, 1558, 1467, 1432, 1417, 1392, 1201, 1168, 1147, 1106, 701.

[0073] 2. The preparation method of the pyrimidine-pyridine bis-hydrazone Zn(II) complex is as follows:

[0074] (1) Accurately weigh 0.025 mmol of the ligand 2-phenyl-4,6-bis(pyridine-2-carboxaldehyde)pyrimidine hydrazone and dissolve it in 10 mL of a mixed solvent (the mixed solvent is composed of methanol and acetonitrile with a volume ratio of 2:1) to obtain a ligand solution;

[0075] (3) Accurately weigh 0.03 mmol of ferrous perchlorate hexahydrate and add it to the ligand solution, and stir at room temperature for 2 h;

[0076] (4) Filter, and slowly volatilize the filtrate at room temperature. After about 7 days, dark red block crystals will precipitate, which is the pyrimidine-pyridine bis-hydrazone Zn(II) complex, with a yield of 51.2% and a purity of 98%.

[0077] The infrared spectrum (cm -1, KBr): 3095, 1633, 1610, 1598, 1567, 1562, 1548, 1533, 1509, 1481, 1469, 1444, 1407, 1294, 1228, 1193, 1155, 1116, 1097, 1012, 933, 775, 701, 624 (such as Figure 6 as shown).

[0078] Experimental Example

[0079] The above ligands and complexes were used in an in vitro anti-tumor activity experiment. The method for measuring the in vitro anti-tumor activity is as follows:

[0080] The MTT colorimetric method was used in the experiment. The light absorption value was measured at a wavelength of 570 nm using an enzyme-linked immunosorbent assay detector, and the cell survival rate and IC 50 value were further calculated.

[0081] (1) Cell seeding: Human breast cancer cells MCF-7, lung cancer cells A549, and normal cells HL-7702 were used as experimental cells. The number of cells per well was adjusted to 5000 according to Equation 1 and seeded into a 96-well plate. Each plate was set with a blank group (only adding complete medium without adding cells), a negative control group (cell group without adding drugs), and drug treatment groups with drug concentrations of 20 μg / mL, 10 μg / mL, 5 μg / mL, 2.5 μg / mL, and 1.25 μg / mL (cell groups of the ligand prepared in Example 1 of the present invention and the complex prepared in Example 2), with 4 replicates in each group. The inhibition rate at each concentration was calculated according to Equation 2. The experimental methods for the control example complex and the positive control Cisplatin were the same as above.

[0082] (2) After culturing the cells for 24 h and successful adherent growth, they were taken out of the incubator and the original medium was aspirated. 200 μL of complete medium was added to the blank group and the control group, and 200 μL of the drug was added to each well of the drug treatment groups in the order of the diluted drug concentrations. 200 μL of PBS was added around the perimeter to ensure a moist environment for cell culture.

[0083] (3) Drug action: Put it into the incubator and continue to culture for 48 h. After 48 h, take out the 96-well plate, and add 20 μL of 5 mg / mL MTT to each well (pay attention to avoiding light during the operation).

[0084] (4) Continue to culture in the incubator for 4 h. Carefully aspirate the original medium to avoid taking out the cells. Add 150 μL of DMSO to each well in turn, gently blow the cells to fully dissolve the crystal particles (try to avoid generating bubbles during the pipetting process). Shake on a shaker for about 10 min. At a wavelength of 490 nm of the microplate reader, accurately measure the optical density value (OD value) of each well. Finally, calculate the IC50 value of the drug.

[0085]

[0086] Inhibition rate = (negative control group - (drug - added group - blank)) / (negative control group - blank) (Equation 2)

[0087] The IC 50 (μM) values of the in vitro anti - tumor activity of the complex prepared in Example 2 of the present invention are shown in Table 3, and the bar chart is shown in Figure 7 .

[0088] Table 3 IC 50 values (μM) of the ligand in Example 1, the complex in Example 2, the complex in the control example and cisplatin against 2 kinds of tumor cells and normal cells

[0089]

[0090] Note: "--" indicates that the sample has no inhibitory effect on the experimental cells.

[0091] From the measurement results of the in vitro anti - tumor activity experiment, the four - nuclear node - shaped Zn(II) complex prepared in the present invention has significant inhibitory effects on the proliferation of human breast cancer cells MCF - 7 and lung cancer cells A549. The IC50 values are only 2.83 μM and 3.83 μM respectively. The inhibitory activity is significantly stronger than that of the positive control drug cisplatin, and it has no cytotoxicity to normal cells HL - 7702. The complex in the control example also has a relatively significant inhibitory effect on the proliferation of MCF - 7 and A549 tumor cells, but the inhibitory activity is significantly inferior to the Zn(II) complex of the present invention, and it has greater toxicity to normal liver cells HL - 7702. At the same time, it is found that the four - nuclear node - shaped Zn(II) complex prepared in Example 2 of the present invention also has a stronger inhibitory effect on tumor cells than the ligand alone. This shows that the four - nuclear node - shaped Zn(II) complex synthesized in the present invention has obvious advantages and exhibits excellent in vitro anti - tumor activity.

[0092] In summary, the four - nuclear node - shaped Zn(II) complex prepared in Example 2 of the present invention exhibits excellent in vitro anti - tumor activity, showing a positive synergistic effect after the ligand coordinates with Zn(II) ions. This complex has potential medicinal value and is expected to be used in the preparation of anti - tumor drugs.

[0093] The above is only a preferred specific embodiment of the present application, but the protection scope of the present application is not limited thereto. Any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed in the present application should be covered by the protection scope of the present application. Therefore, the protection scope of the present application should be subject to the protection scope of the claims.

Claims

1. A tetra-nuclear nodal Zn(II) complex with anti-tumor activity, characterized in that, The molecular formula of the tetranuclear nodular Zn(II) complex is [Zn4 II (C 16 H 12 Br2N8-H)4](ClO4)4·8CH3OH·5H2O; The ligand of the tetranuclear nodular Zn(II) complex is 4,6-bis(6-bromopyridine-2-carbaldehyde)pyrimidine hydrazone, with the molecular formula C 16 H 12 Br2N8, and the structural formula is shown in Formula (I):

2. The tetra-nuclear nodal Zn(II) complex with anti-tumor activity according to claim 1, characterized in that, The tetranuclear nodular Zn(II) complex is in the tetragonal crystal system, space group P4(2) / nmc, and the unit cell parameters are as follows: α = 90°, β = 90°, γ = 90°, 3. A method for preparing a tetranuclear nodal Zn(II) complex with antitumor activity as described in any one of claims 1-2, characterized in that, It includes the following steps: 1) Dissolve the ligand 4,6-bis(6-bromopyridine-2-carbaldehyde)pyrimidine hydrazone in a mixed solvent of methanol and acetonitrile to obtain a ligand solution; 2) Add zinc perchlorate hexahydrate to the ligand solution and stir evenly; 3) Filter, and let it volatilize naturally at room temperature until red block crystals precipitate, which is the tetranuclear nodular Zn(II) complex; The preparation method of the ligand 4,6-bis(6-bromopyridine-2-carbaldehyde)pyrimidine hydrazone includes the following steps: 1) Disperse 4,6-dichloropyrimidine in hydrazine hydrate and stir at room temperature. Heat the obtained mixture until white solid gradually precipitates to obtain a crude product of 4,6-dihydrazinopyrimidine intermediate; 2) Wash the crude product of 4,6-dihydrazinopyrimidine intermediate with a mixed solvent of ethanol and water to obtain 4,6-dihydrazinopyrimidine intermediate; 3) Dissolve 4,6-dihydrazinopyrimidine intermediate and 6-bromopyridine-2-carbaldehyde in absolute ethanol respectively and mix them. Stir, reflux in an oil bath. After the reaction is completed, filter, wash, and purify by column chromatography to obtain the ligand 4,6-bis(6-bromopyridine-2-carbaldehyde)pyrimidine hydrazone; the molar ratio of the 4,6-dihydrazinopyrimidine intermediate to 6-bromopyridine-2-carbaldehyde is 1∶2.

1.

4. The preparation method according to claim 3, wherein The volume ratio of the methanol to the acetonitrile is 2∶1; the molar ratio of the 4,6-bis(6-bromopyridine-2-carbaldehyde)pyrimidine hydrazone to zinc perchlorate hexahydrate is 1∶1.

2.

5. Use of a tetranuclear nodular Zn(II) complex with antitumor activity as described in any one of claims 1-2 in the preparation of antitumor drugs.

6. The application according to claim 5, wherein The tumor cells in the antitumor drugs include human breast cancer cells MCF-7 or lung cancer cells A549.

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