CN106749016A - A kind of ethidium bromide derivative and its preparation and the application in antitumor - Google Patents

Abstract

The invention discloses an ethidium bromide derivative and its preparation and application in antitumor, belonging to the technical field of medicine. The general structural formula of the ethidium bromide derivative of the present invention is as follows, wherein R is H or a halogen element. The ethidium bromide derivative of the present invention can realize the targeted enrichment of tumor cells, has a mitochondrial targeting effect, has a good selective inhibitory effect on tumor cells, and can be used for preparing antitumor drugs. The preparation of the ethidium bromide derivative of the invention is simple and efficient, and has great medical application value.

Description

A kind of ethidium bromide derivative and its preparation and application in antitumor

technical field

The invention belongs to the technical field of medicine, and in particular relates to an ethidium bromide derivative and its preparation and application in antitumor.

Background technique

Tumor is a major disease that threatens human health, and targeted tumor therapy is a major topic in the fields of clinical medicine, biomedicine and life science research. Drug therapy is an effective method to inhibit tumor growth and improve the quality of life of patients, and is widely used in clinical cancer treatment. Traditional antineoplastic drugs include doxorubicin, paclitaxel, cisplatin, camptothecin, etc. However, these anti-tumor drugs have poor selectivity for tumor treatment, thus causing relatively large toxic and side effects during the treatment process. Moreover, these therapeutic drugs cannot effectively reach the target, resulting in a lower therapeutic effect. In order to improve the therapeutic effect on tumors, the method of increasing the dosage is usually adopted, which will further lead to multi-drug resistance of tumor cells, and finally lead to the failure of tumor treatment. Therefore, improving the ability of anti-tumor drugs to target and enrich tumor cells and their sites of action, and to develop highly effective anti-tumor drugs will greatly promote the progress of tumor treatment.

Contents of the invention

The object of the present invention is to provide an ethidium bromide derivative, its preparation method and its application in the preparation of antitumor drugs.

The object of the present invention is achieved through the following technical solutions:

A kind of ethidium bromide derivative, its general structural formula is as follows:

Wherein, R is H or a halogen element, and the halogen element is F, Cl, Br. Preferably, R is H or Cl.

The preparation method of described ethidium bromide derivatives, comprises the steps:

(1) Ethidium bromide (EB) was dissolved in a mixed solvent of trifluoroacetic acid/acetonitrile/dichloromethane with a volume ratio of 0.005-0.05:0.5-2:3-5, under nitrogen protection, at 0-4°C Stir for 5-10 minutes.

(2) Add sodium nitrite to the mixture obtained in step (1), and keep it at 0°C-4°C for 5-10 minutes.

(3) Add sulfamic acid to the reaction solution obtained in step (2), and keep it at 0-4°C for 5-10 minutes.

(4) Dissolve N,N-diethylaniline or N,N-bis(2-chloroethyl)aniline in trifluoroacetic acid/acetonitrile/difluoroacetic acid with a volume ratio of 0.005-0.05:0.5-2:3-5 Add the mixed solvent of methyl chloride to the reaction solution obtained in step (3), keep it at 0-4°C for 60-120 minutes to obtain the ethidium bromide derivative.

The volume ratio of trifluoroacetic acid, acetonitrile, and dichloromethane in the above-mentioned trifluoroacetic acid/acetonitrile/dichloromethane mixed solvent is preferably 0.01:1:4.

A pharmaceutically acceptable salt of the aforementioned ethidium bromide derivative. The ethidium bromide derivative has a good targeting effect on tumor cells and their subcellular organelles, and can effectively inhibit the growth of tumor cells. Based on this, the ethidium bromide derivatives or pharmaceutically acceptable salts thereof can be used to prepare antitumor drugs.

An antitumor drug, comprising the above ethidium bromide derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient of the ethidium bromide derivative.

Compared with the prior art, the present invention has the following advantages and effects: the ethidium bromide derivatives of the present invention can achieve targeted enrichment of tumor cells, and have a mitochondrial targeting effect, and have good selective inhibition of tumor cells By changing the membrane potential of the mitochondria, increasing the level of oxidative free radicals in the cell, reducing the level of reduced glutathione in the cell, reducing the level of ATP in the cell, resulting in the release of cytochrome C in the mitochondria, and finally inducing Apoptosis. In addition, the preparation of such molecules is simple and efficient, and has great medical application value.

Description of drawings

Figure 1 is the electrospray mass spectrum of compound 1.

Figure 2 is the electrospray mass spectrum of compound 2.

Fig. 3 is a fluorescent micrograph of breast cancer cells and Vero cells cultured in a medium containing anti-tumor compound 2 labeled with Hoechst33342.

Fig. 4 is a fluorescent micrograph of breast cancer cells labeled with MitoTracker Green after being cultured in a medium containing anti-tumor compound 2.

Figure 5 is a diagram showing the inhibition of cell activity of (A) breast cancer cells and (B) Vero cells by EB, anti-tumor compound 1 and anti-tumor compound 2, respectively.

Fig. 6 is the fluorescent micrographs of breast cancer cells labeled with JC-1 dye after being cultured in the medium containing anti-tumor compound 2 for different periods of time. 1-4 from left to right in the figure are: 1 is JC-1 monomer fluorescent confocal, 2 is JC-1 polymer fluorescent confocal, 3 is the overlap of 1 and 2, 4 is the corresponding arrow in 3 Fluorescence intensity at JC-1.

Fig. 7 is a graph showing the statistical analysis of fluorescence labeled with JC-1 dye after breast cancer cells were cultured in the medium containing anti-tumor compound 2 for different periods of time. Figure A is the fluorescence ratio of JC-1 monomer and JC-1 polymer in breast cancer cells treated with anti-tumor compound 1 or anti-tumor compound 2 for different time, and Figure B is the fluorescence ratio of breast cancer cells treated with EB and anti-tumor compound respectively Fluorescence intensity of JC-1 monomers in cells after 6 hours of treatment with 1 or antitumor compound 2.

Fig. 8 is a fluorescent micrograph of breast cancer cells cultured with medium containing EB, anti-tumor compound 1 and anti-tumor compound 2 and detected by DCFH-DA dye.

Fig. 9 is a graph showing fluorescence statistical analysis of breast cancer cells detected by DCFH-DA dye after being cultured in medium containing EB, anti-tumor compound 1 and anti-tumor compound 2 respectively.

Fig. 10 is an analysis diagram of the content of reduced glutathione in breast cancer cells cultured in culture medium containing EB, anti-tumor compound 1 and anti-tumor compound 2 respectively.

Fig. 11 is an analysis diagram of the ATP content in the cells after the breast cancer cells are cultured with the medium containing EB, anti-tumor compound 1 and anti-tumor compound 2 respectively.

Fig. 12 is an analysis diagram of the relative content of cytochrome C in the cytoplasm of breast cancer cells cultured with the medium containing anti-tumor compound 1.

Fig. 13 is an analysis diagram of the relative content of cytochrome C in the mitochondria of breast cancer cells cultured with the medium containing anti-tumor compound 1.

Fig. 14 is an analysis chart of the relative content of caspase-3 in breast cancer cells cultured with EB, anti-tumor compound 1 and anti-tumor compound 2 respectively.

Fig. 15 is a diagram showing the change of tumor volume over time within 13 days of mouse culture after treating tumor-forming mice with PBS, EB, anti-tumor compound 1 or anti-tumor compound 2.

Fig. 16 is a picture of the tumors of mice cultured for 13 days after treating tumor-forming mice with PBS, EB, anti-tumor compound 1 or anti-tumor compound 2.

Fig. 17 is a graph showing the tumor weight of mice cultured for 13 days after treating tumorigenic mice with PBS, EB, antitumor compound 1 or antitumor compound 2.

Fig. 18 is a graph showing the change of mouse body weight over time after 13 days of mouse culture after treating tumor-forming mice with PBS, EB, anti-tumor compound 1 or anti-tumor compound 2.

detailed description

The present invention will be described in further detail below in conjunction with the examples, but the embodiments of the present invention are not limited thereto.

Example 1

Synthesis of Antitumor Drug Compound 1:

(1) EB (230 mg) was dissolved in 50 mL of a mixed solvent of trifluoroacetic acid/acetonitrile/dichloromethane with a volume ratio of 0.01:1:4. The mixture was protected with nitrogen and stirred at 0°C for 10 minutes.

(2) Sodium nitrite (150 mg) was added to the mixture obtained in step (1), and the mixture was kept at 0°C and stirred for 5 minutes.

(3) Add sulfamic acid (200mg) into the reaction solution obtained in step (2), and keep stirring at 0°C for 10 minutes.

(4) Dissolve N,N-diethylaniline (200 μL) in 2 mL of trifluoroacetic acid/acetonitrile/dichloromethane mixed solvent with a volume ratio of 0.01:1:4, and add it to the reaction solution obtained in step (3) , kept stirring at 0°C for 60 minutes.

(5) After the reaction, the reaction solution obtained in step (4) was diluted with dichloromethane, washed with water three times, and the organic phase was collected and dried overnight with dichloromethane.

(6) The obtained product was purified by column chromatography, and the eluent was a methanol/dichloromethane mixed solvent with a volume ratio of 1:9.

(7) The molecular structure of the compound was characterized by electrospray mass spectrometry, and the obtained product was stored at -20°C in the dark.

The results of electrospray mass spectrometry are shown in Figure 1, which proves the successful synthesis of compound 1.

Example 2

Synthesis of antitumor drug compound 2:

(1) EB (230 mg) was dissolved in 50 mL of a mixed solvent of trifluoroacetic acid/acetonitrile/dichloromethane with a volume ratio of 0.01:1:4. The mixture was protected with nitrogen and stirred at 0°C for 5 minutes.

(2) Sodium nitrite (150 mg) was added to the mixture obtained in step (1), and the mixture was kept at 0° C. and stirred for 10 minutes.

(3) Add sulfamic acid (200mg) into the reaction solution obtained in step (2), keep stirring at 0°C for 5 minutes.

(4) Dissolve N,N-bis(2-chloroethyl)aniline (200 μL) in 2 mL of trifluoroacetic acid/acetonitrile/dichloromethane mixed solvent with a volume ratio of 0.01:1:4, and add to step (3 ) in the resulting reaction solution, kept stirring at 0°C for 60 minutes.

(5) After the reaction, the reaction solution obtained in step (4) was diluted with dichloromethane, washed with water three times, and the organic phase was collected and dried overnight with dichloromethane.

(6) The obtained product was purified by column chromatography, and the eluent was a methanol/dichloromethane mixed solvent with a volume ratio of 1:9.

(7) The molecular structure of the compound was characterized by electrospray mass spectrometry, and the obtained product was stored at -20°C in the dark.

The results of electrospray mass spectrometry are shown in Figure 2, which proves the successful synthesis of compound 2.

Example 3

Breast cancer cells (4T1 cells) and African green monkey kidney cells (COS7 cells) were inoculated into confocal small dishes at a density of 1×10 ⁵ cells/well, and cultured in 1 mL RPMI-1640 medium at 37°C . After 24 hours, the anti-tumor compound 2 was dissolved in the medium, and 1 mL of the medium containing the anti-tumor compound 2 (20 μmol/L) was added to the breast cancer cells and Vero cells. After culturing for 2 hours, the medium containing the anti-tumor compound 2 was aspirated, the cells were washed three times with PBS buffer solution, and the nuclei were labeled with Hoechst 33342, and then the fluorescence intensity of the anti-tumor compound 2 in the cells was observed with a confocal laser microscope.

The results are shown in Figure 3, compared with the African green monkey kidney cells, the anti-tumor compound 2 has a better enrichment effect on breast cancer cells, indicating that the anti-tumor compound 2 has a good targeted enrichment effect on tumor cells.

Example 4

Breast cancer cells were seeded into confocal small dishes at a density of 1×10 ⁵ cells/well, and cultured in 1 mL of culture medium at 37°C. After 24 hours, the antitumor compound 2 was dissolved in the medium, and 1 mL of the medium containing the antitumor compound 2 (20 μmol/L) was added to the breast cancer cells. After culturing for 2 hours, the medium containing anti-tumor compound 2 was aspirated, the cells were washed three times with PBS buffer solution, and the mitochondria were labeled with mitochondrial dye (MitoTracker Green), and then the distribution of anti-tumor compound 2 in the cells was observed by confocal laser microscopy.

The results are shown in Figure 4, the fluorescence of the anti-tumor compound 2 in tumor cells overlaps well with the fluorescence of the mitochondrial dye, which proves that the anti-tumor compound 2 has the effect of targeting the mitochondria of tumor cells.

Example 5

Breast cancer cells and Vero cells were seeded in a 96-well plate at a density of 6000 cells/well, and cultured in 100 μL medium for 24 hours. Then, 100 μL of solutions containing EB, antitumor compound 2, and antitumor compound 1 at different concentrations prepared in culture medium were added to each well. All cells were cultured at 37°C for 48 hours in the dark. Then 20 μL of 5 mg/mL MTT (MTT dissolved in PBS buffer) was added to each well. After 4 hours of co-cultivation, the medium was aspirated and 150 μL of DMSO was added. The microplate reader measured the absorbance at 570 nanometers in each well, calculated the cell survival rate, and then obtained the toxicity of EB, anti-tumor compound 2, and anti-tumor compound 1 to breast cancer cells and African green monkey kidney cells.

The results are shown in Figure 5, anti-tumor compound 2 and anti-tumor compound 1 are extremely toxic to breast cancer cells and Vero cells. And compared with the African green monkey kidney cells, anti-tumor compound 2 and anti-tumor compound 1 have greater toxicity to breast cancer cells; anti-tumor compound 1 has greater cytotoxicity than anti-tumor compound 2. Thus it was proved that anti-tumor compound 2 and anti-tumor compound 1 have higher toxicity to tumor cells.

Example 6

Breast cancer cells were seeded in confocal small dishes at a density of 1×10 ⁵ cells/well, and cultured in 1 mL of culture medium at 37°C. After 24 hours, the antitumor compound (2 or 1) was dissolved in the medium, and 1 mL of the medium containing the antitumor compound (20 μmol/L) was added to the breast cancer cells. After culturing for 1 hour, the medium containing anti-tumor compounds was aspirated, and the cells were washed three times with PBS buffer solution. After the cells were cultured for 1 hour, 2 hours, 6 hours, 12 hours and 23 hours, the mitochondrial dye (JC- 1) After staining for half an hour, observe the distribution of JC-1 fluorescence in the cells with a confocal laser microscope. At the same time, the change of JC-1 fluorescence intensity in cells over time was analyzed by ImageJ.

The results are shown in Figure 6, when the anti-tumor compound 2 interacted with the cells for a short period of time, the mitochondrial membrane potential of the tumor cells did not change, but the destruction of the mitochondrial membrane of the tumor cells was enhanced with the increase of the culture time. At the same time, as shown in Figure 7A, anti-tumor compound 1 has a stronger damaging effect on the mitochondrial membrane of cancer cells than anti-tumor compound 2. Therefore, both antitumor compound 2 and antitumor compound 1 have the effect of disrupting mitochondrial membrane potential.

Example 7

Breast cancer cells were seeded in a six-well plate at a density of ¹ ×105 cells/well, and cultured in 1 mL of medium at 37°C. After 24 hours, EB, anti-tumor compound 2 and anti-tumor compound 1 were dissolved in the culture medium, and 1 mL of culture medium containing EB, anti-tumor compound 2 or anti-tumor compound 1 (20 μmol/L) was added to the breast cancer cells, respectively. Base or only blank medium was added as a blank control. After culturing for 1 hour, the culture medium containing EB, anti-tumor compound 2 and anti-tumor compound 1, and the blank medium were aspirated, and the cells were washed three times with PBS buffer solution. After the cells were cultured for another 6 hours, the mitochondrial dye (JC- 1) Stain for half an hour, and then analyze the distribution of JC-1 monomer fluorescence in the cells by flow cytometry.

The results are shown in Figure 7B, anti-tumor compound 2 and anti-tumor compound 1 have higher JC-1 monomer fluorescence, while EB is almost the same as the blank control group, thus proving again that anti-tumor compound 2 and anti-tumor compound 1 have mitochondrial Ability to disrupt membrane potential.

Example 8

Breast cancer cells were seeded in confocal small dishes at a density of 1×10 ⁵ cells/well, and cultured in 1 mL of culture medium at 37°C. After 24 hours, EB, anti-tumor compound 2 and anti-tumor compound 1 were dissolved in the culture medium, and 1 mL of culture medium containing EB, anti-tumor compound 2 or anti-tumor compound 1 (20 μmol/L) was added to the breast cancer cells, respectively. Base or only blank medium was added as a blank control. After culturing for 1 hour, the medium containing EB, antitumor compound 2 and antitumor compound 1, and the blank medium were aspirated, and the cells were washed three times with PBS buffer solution. -DA was co-cultured for half an hour, and then the fluorescence intensity in the cells was observed with a confocal laser microscope. At the same time, the intracellular fluorescence intensity under different conditions was analyzed by ImageJ.

The results are shown in Figure 8, the fluorescence intensities in blank cells and cells co-cultured with EBs were lower, while the fluorescence intensities in cells co-cultured with anti-tumor compound 2 and anti-tumor compound 1 were higher, thus proving that the anti-tumor Tumor compound 2 and antitumor compound 1 have the ability to enhance intracellular active free radicals. At the same time, as shown in Figure 9, the active free radicals in the cells after the action of anti-tumor compound 1 are higher than the active free radicals after the action of anti-tumor compound 2, which proves that the anti-tumor compound 1 has a stronger anti-tumor effect. effect.

Example 9

Breast cancer cells were seeded in a six-well plate at a density of ¹ ×105 cells/well, and cultured in 1 mL of medium at 37°C. After 24 hours, EB, antitumor compound 2, and antitumor compound 1 were dissolved in the medium, respectively, and 1 mL of medium containing EB, antitumor compound 2, or antitumor compound 1 (20 μmol/L) was added to the breast cancer cells Or just add blank culture medium as blank control. After culturing for 1 hour, the culture medium containing EB, anti-tumor compound 2 and anti-tumor compound 1, and the blank medium were aspirated, and the cells were washed three times with PBS buffer solution, and the cells were cultured for another 24 hours, and then the cells were lysed, and the cells were lysed at 6000 rpm. After centrifugation for 5 minutes, 50 μL of the supernatant was added to 200 μL Ellman detection reagent, and the absorbance at 406 nanometers after different sample treatments was detected with a microplate reader.

The results are shown in Figure 10, the reduced glutathione levels in tumor cells after the action of anti-tumor compound 2 and anti-tumor compound 1 were significantly reduced, proving again that anti-tumor compound 2 and anti-tumor compound 1 have the ability to regulate intracellular oxidation Ability to restore internal pressure.

Example 10

Breast cancer cells were seeded in a six-well plate at a density of ¹ ×105 cells/well, and cultured in 1 mL of medium at 37°C. After 24 hours, EB, antitumor compound 2, and antitumor compound 1 were dissolved in the medium, respectively, and 1 mL of medium containing EB, antitumor compound 2, or antitumor compound 1 (20 μmol/L) was added to the breast cancer cells Or just add blank culture medium as blank control. After culturing for 1 hour, suck out the medium containing EB, antitumor compound 2 and antitumor compound 1, and the blank medium, wash the cells three times with PBS buffer solution, and culture the cells for another 24 hours, then lyse the cells and detect with ATP The kit detects the ATP content in different samples.

The results are shown in Figure 11, the ATP levels in tumor cells after the action of anti-tumor compound 2 and anti-tumor compound 1 were significantly reduced, proving that anti-tumor compound 2 and anti-tumor compound 1 have the ability to inhibit the synthesis of ATP in tumor cells.

Example 11

Breast cancer cells were seeded in a six-well plate at a density of ¹ ×105 cells/well, and cultured in 1 mL of medium at 37°C. After 24 hours, the anti-tumor compound 1 was dissolved in the medium, and 1 mL of the medium containing the anti-tumor compound 1 (20 μmol/L) was added to the breast cancer cells or only a blank medium was added as a blank control. After culturing for 6 hours, the medium containing anti-tumor compound 1 and the blank medium were aspirated, the cells were washed three times with PBS buffer solution, and the cells were cultured for another 24 hours to extract protein, and western blot was used to analyze the cytochrome in tumor cell cytoplasm and mitochondria The relative content of C.

The results are shown in FIG. 12 , the level of cytochrome C in the cytoplasm of tumor cells treated with antitumor compound 1 was higher than that of control blank cells. At the same time, as shown in FIG. 13 , the level of cytochrome C in mitochondria of tumor cells treated with antitumor compound 1 was lower than that of control blank cells. The above results indicate that antitumor compounds can induce the release of cytochrome c from mitochondria.

Example 12

Breast cancer cells were seeded in a six-well plate at a density of ¹ ×105 cells/well, and cultured in 1 mL of medium at 37°C. After 24 hours, EB, antitumor compound 2, and antitumor compound 1 were dissolved in the medium, respectively, and 1 mL of medium containing EB, antitumor compound 2, or antitumor compound 1 (20 μmol/L) was added to the breast cancer cells Or just add blank culture medium as blank control. After culturing for 6 hours, suck out the culture medium containing EB, anti-tumor compound 2 and anti-tumor compound 1, and the blank medium, wash the cells three times with PBS buffer solution, culture the cells for another 24 hours, extract protein, and analyze the tumor by western blot The relative content of activated caspase-3 in cells.

The results are shown in Figure 14, the expression of activated caspase-3 in tumor cells after the action of anti-tumor compound 2 and anti-tumor compound 1 is increased, which proves that anti-tumor compound 2 and anti-tumor compound 1 can induce apoptosis of tumor cells .

Example 13

5-6 week old mice (BALB/c) were subcutaneously injected with 100 μL of breast cancer cell suspension in PBS containing 1×10 ⁶ cells in the outer thigh to create tumors, when the tumor volume grew to about 200 mm ³ . The mice were randomly divided into 4 groups. PBS and EB, antitumor compound 2 and antitumor compound 1. The opposite material was injected on the first and fifth day, respectively. The tumor volume was measured every other day, and the body weight of the mice was weighed. The tumor volume is calculated according to the formula V=W ² ×L/2, where W is the shorter tumor width, L is the longer tumor width, and the relative tumor volume (V/V ₀ , V is the real-time tumor volume, V ₀ is Tumor volume before treatment) to reflect changes in tumor volume. After the mice were cultured to the 13th day, the tumors of the mice were removed, and the weights of the tumors of the mice were measured respectively.

The results are shown in Figure 15, Figure 16 and Figure 17, the tumor growth of the mice treated with anti-tumor compound 2 and anti-tumor compound 1 was inhibited, and the anti-tumor compound 1 had a better tumor inhibitory effect than the tumor compound 2. At the same time, as shown in Figure 18, the weight of the mice did not change significantly with the treatment effect, indicating that the anti-tumor compound 2 and the anti-tumor compound 1 had no strong toxic side effects on the mice.

The above-mentioned embodiment is a preferred embodiment of the present invention, but the embodiment of the present invention is not limited by the above-mentioned embodiment, and any other changes, modifications, substitutions, combinations, Simplifications should be equivalent replacement methods, and all are included in the protection scope of the present invention.

Claims (8)

1. an ethidium bromide derivative, characterized in that: the general structural formula is as follows: Wherein, R is H or a halogen element. 2. The ethidium bromide derivative according to claim 1, characterized in that: R is H or Cl. 3. the preparation method of ethidium bromide derivative described in claim 1, is characterized in that: comprise the steps: (1) Ethidium bromide was dissolved in a mixed solvent of trifluoroacetic acid/acetonitrile/dichloromethane with a volume ratio of 0.005-0.05:0.5-2:3-5, protected by nitrogen gas, and stirred at 0-4°C for 5 -10 minutes; (2) Sodium nitrite is added to the mixture obtained in step (1), and kept at 0-4°C for 5-10 minutes; (3) adding sulfamic acid to the reaction solution obtained in step (2), keeping it at 0-4°C for 5-10 minutes; (4) Dissolve N,N-diethylaniline or N,N-bis(2-chloroethyl)aniline in trifluoroacetic acid/acetonitrile/difluoroacetic acid with a volume ratio of 0.005-0.05:0.5-2:3-5 Add the mixed solvent of methyl chloride to the reaction solution obtained in step (3), keep it at 0-4°C for 60-120 minutes to obtain the ethidium bromide derivative. 4. the preparation method of ethidium bromide derivative according to claim 3 is characterized in that: the volume ratio of trifluoroacetic acid, acetonitrile, methylene chloride in described trifluoroacetic acid/acetonitrile/methylene chloride mixed solvent It is 0.01:1:4. 5. A pharmaceutically acceptable salt of the ethidium bromide derivative as claimed in claim 1. 6. Use of the ethidium bromide derivative as claimed in claim 1 or the salt as claimed in claim 5 in the preparation of antitumor drugs. 7. An antitumor drug, characterized in that it comprises the ethidium bromide derivative as claimed in claim 1 or the salt as claimed in claim 5. 8. The antitumor drug according to claim 7, characterized in that it comprises a pharmaceutically acceptable carrier or excipient of the ethidium bromide derivative as claimed in claim 1.