Aromatic diamine derivative, preparation method thereof and method for improving active oxygen generation capability of aromatic diamine derivative

Abstract

The invention discloses an aromatic diamine derivative, a preparation method of the aromatic diamine derivative and a method for improving the active oxygen generation capacity of the aromatic diamine derivative, and belongs to the technical field of organic synthesis and biological medicine. A reaction type donor-receptor interaction structure system is developed, the preparation method is simple, NO responsiveness is achieved, photodynamic therapy can be started in a tumor microenvironment with high NO expression, after the aromatic diamine derivative and NO or an NO donor are subjected to a single electron transfer oxidation reaction to generate a triazole derivative, the active oxygen generation capacity is improved, and the photodynamic therapy effect is improved. By targeting the endoplasmic reticulum, the killing effect on tumor cells is further improved, and the nano-material has a good application prospect in the aspect of tumor treatment.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis and biomedicine, and specifically relates to an aromatic diamine derivative and a preparation method thereof and a method for improving the active oxygen generation capacity thereof. Background Art

[0002] Cancer has long been a major problem that seriously troubles human health and life safety. Chemotherapy is one of the important means of cancer treatment at present, but traditional chemotherapy strategies have problems such as poor targeting and strong toxic side effects. After entering the patient's body, chemotherapy drugs are often difficult to accurately target only cancer cells, but will indiscriminately affect normal cells in the body. In order to improve the targeting and therapeutic effect of tumor treatment, many new anti-tumor strategies have been developed. Photodynamic therapy, immunotherapy, gene therapy and targeted therapy have gradually become research hotspots. Among them, photodynamic therapy (PDT) is the use of photosensitive drugs for photoactivation to treat tumors. The photosensitizer taken by tissues is irradiated with light of a specific wavelength, and sensitized to produce reactive oxygen, causing irreversible damage to tumor cells, and ultimately leading to the death of cancer cells. PDT has the advantages of few side effects, less trauma, good selectivity, repeatable treatment, good adaptability and not easy to produce drug resistance. It has been applied to the treatment of surface tumors and intracavitary tumors.

[0003] For example, a Chinese patent document with publication number CN118255762A discloses an AIE-type thermally activated delayed fluorescence photosensitizer mainly used for photodynamic therapy, which is composed of an indolizine acceptor unit and two identical heteroaromatic amines as donor units, has obvious triplet exciton activity, and has a good photodynamic therapy effect. A Chinese patent document with publication number CN115232145A discloses an AIE-type organic photosensitizer, which uses triphenylamine as an electron donor, pyridinium salt as an electron acceptor, and thiophene as an electron π bridge. The photosensitizer shows strong phototoxicity under the irradiation conditions of LED white light.

[0004] However, photodynamic therapy is limited by the characteristics of photosensitizer drugs and the complexity of the tumor microenvironment. The photosensitizer drugs currently used have defects such as poor tissue penetration, low efficiency of reactive oxygen species (ROS) generation, and poor stability. On the other hand, the hypoxic environment in tumor tissue limits the generation of reactive oxygen species, which in turn affects the therapeutic effect of photosensitizers. Therefore, it is particularly important to develop new photofunctional materials based on the tumor microenvironment and realize photodynamic therapy initiated by the tumor microenvironment. Summary of the invention

[0005] The invention provides an aromatic diamine derivative, which has a simple preparation method, NO responsiveness, can initiate photodynamic therapy in a tumor microenvironment with high NO expression, and has a good tumor inhibition effect.

[0006] The specific technical solutions adopted are as follows:

[0007] An aromatic diamine derivative, the structural formula of which is shown below:

[0008]

[0009] In the formula, R1 and R2 are both electron donating groups, and R1 and R2 may be the same or different;

[0010] The R1 and R2 are each independently selected from an oxygen-containing heterocyclic aryl group or an oxygen-containing heterocyclic aryl group derivative;

[0011] The aromatic diamine derivative has NO responsiveness (can undergo single electron transfer oxidation reaction with NO to generate triazole derivatives) and photodynamic anti-tumor effect.

[0012] The present invention constructs an intelligent photosensitizing functional material based on a reactive molecular donor-acceptor (DA) strategy, which has NO responsiveness and photodynamic generation capabilities. Combined with the characteristic of high NO expression in the tumor microenvironment, it has good application prospects in tumor treatment.

[0013] Preferably, R1 and R2 are the same; the structural formula of the oxygen-containing heterocyclic aryl group or the oxygen-containing heterocyclic aryl group derivative is any one of the following:

[0014]

[0015] In formula (I), X is an oxygen group element, and R3 is hydrogen, a substituted or unsubstituted straight chain, branched chain or cyclic alkyl chain having 1 to 20 carbon atoms.

[0016] Further preferably, the structural formula of the aromatic diamine derivative is:

[0017]

[0018] Aromatic diamine derivatives with corresponding structural formulas have good tumor inhibition effects. By targeting the endoplasmic reticulum of cells and initiating photodynamic therapy after NO reaction, efficient inhibition of tumor cells is achieved.

[0019] The present invention also provides a method for preparing the aromatic diamine derivative, which specifically comprises the following steps:

[0020] (1) Under an inert gas atmosphere, using the compound 2,5-dibromo-3,4-dinitrothiophene as a raw material, 2,5-dibromo-3,4-dinitrothiophene and a donor compound react to prepare an intermediate; the donor compound contains an R1 group and / or an R2 group, and R1 and R2 are as defined above;

[0021] (2) The intermediate undergoes a reduction reaction to convert the nitro group into an amino group, thereby preparing the aromatic diamine derivative.

[0022] Furthermore, in step (1), the molar ratio of 2,5-dibromo-3,4-dinitrothiophene to the donor compound is 1:2.5-3; and a palladium catalyst and a phosphine ligand are added during the reaction.

[0023] Furthermore, in step (2), a reaction system including an intermediate, zinc powder and ammonium chloride is constructed, and a reduction reaction is carried out under an inert gas atmosphere to prepare the aromatic diamine derivative.

[0024] Preferably, the molar ratio of the intermediate, zinc powder and ammonium chloride is 1:30 to 35:10 to 12. The corresponding reaction system can carry out the reduction reaction at room temperature, the reaction conditions are mild and easy to implement, and under the above preferred conditions, the reduction reaction is conducive to improving the yield.

[0025] The present invention also provides the use of the aromatic diamine derivatives in the preparation of tumor treatment products. The aromatic diamine derivatives have a tumor cell killing effect and a solid tumor inhibition effect, can be used for photodynamic anti-tumor, and have broad application prospects in tumor treatment.

[0026] Furthermore, the tumor treatment product is an NO-activated tumor treatment product.

[0027] The present invention also provides a method for improving the active oxygen generation capability of the aromatic diamine derivative, comprising: allowing the aromatic diamine derivative to undergo a single electron transfer oxidation reaction with NO or an NO donor to generate a triazole derivative to improve its active oxygen generation capability.

[0028] After a large number of experiments, the inventors found that the aromatic diamine derivatives can react spontaneously and efficiently with NO to generate triazole derivatives, resulting in enhanced donor-acceptor interaction of the molecule, reduced energy difference between singlet and triplet states, improved photosensitivity, and can be used for photodynamic therapy initiated by tumor microenvironment, reducing phototoxicity and other toxic side effects.

[0029] Furthermore, the molar ratio of the aromatic diamine derivative to NO or NO donor is 1:0.1-1000, and the reaction is carried out under a certain temperature (temperature higher than 4°C) or white light irradiation (20-40mW / cm 2 ) to react.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] 1. The aromatic diamine derivatives of the present invention have good biocompatibility, low dark toxicity, good endoplasmic reticulum targeting ability and excellent NO response ability.

[0032] 2. The aromatic diamine derivatives of the present invention react with NO in the tumor microenvironment to generate triazole derivatives, which have enhanced reactive oxygen production capabilities and can induce cell death under light conditions, thereby achieving efficient inhibition of tumor cells and solid tumors.

[0033] 3. The aromatic diamine derivatives of the present invention are simple to prepare and highly efficient. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 This is a graph showing the changes in the absorption values ​​of the four compounds under NO donor BNN6 and light conditions.

[0035] Figure 2 This is a characterization diagram of the enhanced ability to produce active oxygen after the compound TA-DTO in the example reacts with NO to generate TT-DTO.

[0036] Figure 3 This is a graph showing the results of co-localization imaging experiments between compounds TA-DPA, TA-TPA, TA-TPAMO, TA-DTO and TN-DTO and cells.

[0037] Figure 4 The statistical chart of cytotoxicity test results, where A is the dark toxicity test of TA-DPA, TA-TPA, TA-TPAMO, and TA-DTO without white light, and B is the dark toxicity test of TA-DPA, TA-TPA, TA-TPAMO, and TA-DTO with white light (18 mW / cm 2 , 15 minutes) under phototoxicity experiment.

[0038] Figure 5 The figures are the in vivo treatment effect diagrams of TA-DTO, where A is the weight statistics of 4T1 tumor mice under different treatments, B is the relative change statistics of primary tumor volume of 4T1 tumor mice under different treatments, C is a typical photo of tumor resection in 4T1 tumor mice at the end of different treatments, I is the PBS group, II is the PBS+light group; III is the TA-DTO NPs group; IV is the TA-DTO NPs+light group. DETAILED DESCRIPTION

[0039] In order to make the purpose, features and advantages of the present invention more obvious and easy to understand, the following is a detailed description through specific embodiments. In the following description, many specific details are set forth in order to fully understand the present invention. However, the present invention can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without violating the connotation of the present invention, so the present invention is not limited by the specific embodiments disclosed below. The technical features in each embodiment of the present invention can be combined accordingly without conflicting with each other.

[0040] The operating methods in the following examples without specifying specific conditions are usually carried out under conventional conditions or according to the conditions recommended by the manufacturer. The contents not described in detail in this specification belong to the prior art known to professionals in the field. The experimental materials used in the following examples, unless otherwise specified, can be purchased from conventional biochemical reagent companies.

[0041] Comparative Example 1

[0042] The compound TA-DPA was synthesized according to the following synthetic route:

[0043]

[0044] Synthesis of compound TN-DPA: Compound 1 (2,5-dibromo-3,4-dinitrothiophene, 1.66 g, 5.0 mmol), compound 2 (5.26 g, 12.5 mmol) and Pd(PPh3)4 (0.57 g, 0.50 mmol) were dissolved in 120 mL of tetrahydrofuran THF and 120 mL of toluene, and then evacuated under an argon atmosphere. After stirring the resulting mixture at 50 ° C for 10 minutes, 80 mL of degassed K2CO3 (2M) aqueous solution was added, and then refluxed overnight. Stop the reaction, return to room temperature, and evaporate THF and toluene. Dissolve the residual solid with dichloromethane and wash with water (3×100 mL). Extract the organic layer, dry it with anhydrous sodium sulfate, and concentrate the organic layer by rotary evaporation. The product was purified by column chromatography (silica gel) using petroleum ether / dichloromethane (8 / 1, v / v) as the eluent to obtain TN-DPA as an orange solid with a yield of 2.5 g (yield 65.78%).

[0045] The H NMR spectrum data of compound TN-DPA is: 1 H NMR(500MHz,Methylene Chloride-d2)δ7.93(s,4H),7.86(s,2H),7.52(s,4H),7.41(s,4H),7.29(s,7H),7.22(s,4H),7.08(s,3H),6.93(s,4H).

[0046]

[0047] Synthesis of compound TA-DPA: In a 50mL two-necked bottle, weigh compound TN-DPA (1g, 1.31mmol), zinc powder (2.7g, 41.3mmol) and ammonium chloride (0.703g, 13.1mmol), degas, inject nitrogen, inject dichloromethane (7mL) and 90% degassed methanol solution (13mL), and react at room temperature for 4 hours. After the reaction is completed, the reaction solution is filtered with diatomaceous earth, and then extracted with dichloromethane and saturated brine. Collect the organic phase three times. Dry with anhydrous magnesium sulfate, filter the dried organic phase, and remove the solvent by rotary evaporation to obtain a black powder compound TA-DPA, yield: 0.46 g (yield 50.5%).

[0048] The H NMR spectrum data of compound TA-DPA is: 1 H NMR(500MHz,Methylene Chloride-d2)δ7.94(s,4H),7.81(s,2H),7.50(d,J=8.4Hz,4H),7.34(d,J=29.5Hz,8H),7.21(s,4H),7.03(s,8H),6.95(s,2H),3.62(s,4H).

[0049] Comparative Example 2

[0050] The compound TA-TPA was synthesized according to the following synthetic route:

[0051]

[0052] Synthesis of compound TN-TPA: Compound 1 (2,5-dibromo-3,4-dinitrothiophene, 1.66 g, 5.0 mmol), compound 3 (4-(diphenylamino)phenylboronic acid, 3.6 g, 12.5 mmol) and Pd(PPh3)4 (0.57 g, 0.50 mmol) were dissolved in 120 mL of tetrahydrofuran THF and 120 mL of toluene, and then evacuated under an argon atmosphere. After stirring the resulting mixture at 50 ° C for 10 minutes, 80 mL of degassed K2CO3 (2M) aqueous solution was added, and then refluxed overnight. Stop the reaction, return to room temperature, and remove THF and toluene by rotary evaporation. Dissolve the residual solid with dichloromethane and wash with water (3×100 mL). Extract the organic layer, dry it with anhydrous sodium sulfate, and concentrate the organic layer by rotary evaporation. The product was purified by column chromatography (silica gel) using petroleum ether / dichloromethane (6 / 1, v / v) as the eluent to obtain TN-TPA as an orange solid with a yield of 2.54 g (yield 76.96%).

[0053] The H NMR spectrum data of compound TN-TPA is: 1H NMR(500MHz,Methylene Chloride-d2)δ7.40–7.28(m,12H),7.14(dd,J=15.2,7.7Hz,12H),7.02(d,J=8.5Hz,4H).

[0054]

[0055] Synthesis of compound TA-TPA: In a 50mL double-necked flask, weigh compound TN-TPA (1g, 1.51mmol), zinc powder (3.11g, 47.56mmol) and ammonium chloride (0.807g, 15.1mmol), degas, inject nitrogen, inject dichloromethane (7mL) and 90% degassed methanol solution (13mL), and react at room temperature for 4 hours. After the reaction is completed, the reaction solution is filtered with diatomaceous earth, and then extracted with dichloromethane and saturated brine. Collect the organic phase three times. Dry with anhydrous magnesium sulfate, filter the organic phase, and remove the solvent by rotary evaporation to obtain a black powder compound TA-TPA, yield: 0.4 grams (yield 44.44%).

[0056] The H NMR spectrum data of compound TA-TPA is: 1 H NMR(500MHz,Methylene Chloride-d2)δ7.38(d,J=8.3Hz,4H),7.27(t,J=7.7Hz,8H),7.10(dd,J=8.4,6.6Hz,12H),7.04(t,J=7.4Hz,4H),3.66(s,4H).

[0057] Example 1

[0058] The compound TA-DTO was synthesized according to the following synthetic route:

[0059]

[0060] Synthesis of compound TN-DTO: Under anhydrous and deoxygenated conditions, Pd2(dba)3 (0.366 g, 0.4 mmol) and P(o-tol)3 (0.365 g, 1.2 mmol) were added to a solution of compound 1 (2,5-dibromo-3,4-dinitrothiophene, 1.6 g, 5.0 mmol) and compound 5 (5.39 g, 12.5 mmol) in anhydrous toluene (30 mL). The mixture was refluxed at 110 ° C under nitrogen for 24 hours. After cooling to room temperature, the solvent was removed by rotary evaporation, and the crude product was purified by column chromatography (PE / DCM) to obtain the product brown-red solid TN-DTO, yield: 1.5 g (yield 68%).

[0061] The H-NMR spectrum data of compound TN-DTO are: 1 H NMR(500MHz,Chloroform-d)δ6.31(s,2H),4.34–4.29(m,4H),4.27–4.22(m,4H).

[0062]

[0063] Synthesis of compound TA-DTO: In a 50mL double-necked flask, weigh compound TN-DTO (0.5g, 1.1mmol), zinc powder (2.262g, 34.6mmol) and ammonium chloride (0.588g, 11.0mmol) respectively. Degas, inject nitrogen, inject dichloromethane (7mL) and 90% degassed methanol solution (13mL), and react at room temperature for 4 hours. After the reaction is completed, the reaction solution is filtered with diatomaceous earth, and then extracted with dichloromethane and saturated brine. Collect the organic phase three times. Dry with anhydrous magnesium sulfate, filter the organic phase, and remove the solvent by rotary evaporation to obtain a black powder compound TA-DTO, yield: 0.26 grams (yield 59%).

[0064] The H-NMR spectrum data of compound TA-DTO are: 1 H NMR(500MHz,Chloroform-d)δ6.30(s,2H),4.34–4.19(m,8H),3.98–3.64(m,4H).

[0065] Comparative Example 3

[0066] The compound TA-TPAMO was synthesized according to the following synthetic route:

[0067]

[0068] Synthesis of compound TN-TPAMO: Compound 1 (2,5-dibromo-3,4-dinitrothiophene, 1.66 g, 5.0 mmol), compound 4 (5.39 g, 12.5 mmol) and Pd(PPh3)4 (0.577 g, 0.50 mmol) were dissolved in 120 mL tetrahydrofuran THF and 120 mL toluene under argon atmosphere. After stirring the resulting mixture at 50 ° C for 10 minutes, 80 mL of degassed K2CO3 (2M) aqueous solution was added and then refluxed overnight. Stop the reaction, return to room temperature, and evaporate THF and toluene. Dissolve the residual solid with dichloromethane and wash with water (3×100 mL). Extract the organic layer, dry it with anhydrous sodium sulfate, and concentrate the organic layer by rotary evaporation. The product was purified by column chromatography (silica gel) using petroleum ether / dichloromethane (1 / 8, v / v) as the eluent to obtain red solid TN-TPAMO with a yield of 2.6 g (yield 66.67%).

[0069] The H NMR spectrum data of the compound TN-TPAMO is: 1 H NMR(500MHz,Methylene Chloride-d2)δ7.28(d,J=8.6Hz,4H),7.13(d,J=8.6Hz,8H),6.87(dd,J=19.7,8.5Hz,12H),3.80(s,12H).

[0070]

[0071] Synthesis of compound TA-TPAMO: In a 50mL double-necked flask, weigh compound TN-TPAMO (1g, 1.28mmol), zinc powder (2.632g, 40.25mmol) and ammonium chloride (0.685g, 12.8mmol), degas, inject nitrogen inert gas, inject dichloromethane (7mL) and 90% degassed methanol solution (13mL), and react at room temperature for 4 hours. After the reaction is completed, the reaction solution is filtered with diatomaceous earth, and then extracted with dichloromethane and saturated brine. Collect the organic phase three times. Dry with anhydrous magnesium sulfate, filter the organic phase, and remove the solvent by rotary evaporation to obtain a black powder compound TA-TPAMO, yield: 0.4 grams (yield 44.64%).

[0072] The H NMR spectrum data of the compound TA-TPAMO is: 1 H NMR (500MHz, Chloroform-d) δ7.30 (d, J = 8.4Hz, 4H), 7.13–7.04 (m, 8H), 7.01–6.92 (m, 4H), 6.89–6.79 (m, 8H), 3.80 (s, 12H).

[0073] Sample analysis

[0074] (1) Study on the reactivity of aromatic diamine derivatives with NO and photocatalytic cyclization

[0075] After the aromatic diamine derivatives react with NO, the red shift of the absorption spectrum is used to determine the progress of the reaction. The product compounds prepared in the examples and comparative examples were mixed with the NO donor BNN6 (TA-DPA, TA-TPA, TA-TPAMO and TA-DTO were dissolved in THF to a final concentration of 20 μM, and then BNN6 (20 μM) was added), and the changes in the absorption spectrum were detected using an ultraviolet-visible spectrometer. In order to further study the effect of light on the reaction, the trend of the absorption spectrum under light conditions was studied (white light irradiation (35 mW / cm 2 )), see the results Figure 1It can be seen that after adding BNN6, the absorption spectrum of TA-DTO undergoes a significant red shift over time, indicating successful reaction with NO. Similar phenomena can also be observed under light, indicating that light can also promote the reaction. The statistical results of the photophysical properties of the four compounds are shown in Table 1;

[0076] Table 1 Photophysical properties of the four compounds

[0077]

[0078] In addition, from Figure 2 The results show that the ability of TA-DTO to produce active oxygen is improved after the single electron transfer oxidation reaction with NO or NO donor.

[0079] (2) Aromatic diamine derivatives for photodynamic anti-tumor therapy

[0080] 4T1 cells were plated in a cell culture dish and exposed to culture medium containing TA-DPA, TA-TPA, TA-TPAMO, TA-DTO, and TN-DTO for 4 hours. After the cells interacted, they were imaged and characterized using a laser confocal microscope. The results are shown in the figure. Figure 3 The results showed that TA-TPA and TA-DPA were mainly distributed in lysosomes, TA-TPAMO was distributed in lipid droplets, and TA-DTO was distributed in the endoplasmic reticulum.

[0081] The dark toxicity group was as follows: 4T1 cells were plated in a 96-well plate and cultured for 24 hours, then firstly treated with a culture medium solution containing different concentrations of the product compounds of the embodiments and comparative examples for 24 hours, then MTT was added and cultured for 4 hours, and the ultraviolet absorption intensity at 570 nm was measured. The light irradiation group was as follows: 4T1 cells were plated in a 96-well plate and firstly treated with a culture medium solution containing different concentrations of the product compounds of the embodiments and comparative examples for 4 hours, then cultured for 20 hours after irradiation with white light for 20 minutes, then MTT was added and cultured for 4 hours, and the ultraviolet absorption intensity at 570 nm was measured. The results are shown in Table 1. Figure 4 A and B in the figure. The results show that TA-DTO distributed in the endoplasmic reticulum exhibits a significant tumor inhibitory effect at a lower concentration.

[0082] SPF female BALB / c nude mice weighing 16-18 g were selected and 4T1 cells were inoculated subcutaneously in the right hind leg. Each nude mouse was injected with 100 μL of 5×10 6 The cells were irradiated with saline solution, and TA-DTO was injected into the tail vein 7 days later. On the eighth day, the cells were irradiated with white light (light condition: white light: 200 mW / cm 2 , 20 minutes), the weight and tumor size of nude mice were recorded at any time after inoculation. The results are shown in Figure 5 AC in. From the results, it can be seen that TA-DTO has a good tumor inhibition effect.

[0083] The embodiments described above provide a detailed description of the technical solutions of the present invention. It should be understood that the above are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, supplements or similar substitutions made within the scope of the principles of the present invention should be included in the protection scope of the present invention.

Claims

1. An aromatic diamine derivative, characterized in that: The structural formula is shown below: In the formula, R1 and R2 are both electron donating groups, and R1 and R2 may be the same or different; The R1 and R2 are each independently selected from an oxygen-containing heterocyclic aryl group or an oxygen-containing heterocyclic aryl group derivative; The aromatic diamine derivative has NO responsiveness and photodynamic anti-tumor effect.

2. The aromatic diamine derivative according to claim 1, characterized in that R1 and R2 are the same; the structural formula of the oxygen-containing heterocyclic aryl group or the oxygen-containing heterocyclic aryl group derivative is any one of the following: In formula (I), X is an oxygen group element, and R3 is hydrogen, a substituted or unsubstituted straight chain, branched chain or cyclic alkyl chain having 1 to 20 carbon atoms.

3. The aromatic diamine derivative according to claim 1, characterized in that The structural formula of the aromatic diamine derivative is:

4. The method for preparing an aromatic diamine derivative according to any one of claims 1 to 3, characterized in that: The specific steps include: (1) Under an inert gas atmosphere, using the compound 2,5-dibromo-3,4-dinitrothiophene as a raw material, 2,5-dibromo-3,4-dinitrothiophene and a donor compound react to prepare an intermediate; the donor compound contains an R1 group and / or an R2 group, and R1 and R2 are as defined above; (2) The intermediate undergoes a reduction reaction to convert the nitro group into an amino group, thereby preparing the aromatic diamine derivative.

5. The method for preparing an aromatic diamine derivative according to claim 4, characterized in that: In step (1), the molar ratio of 2,5-dibromo-3,4-dinitrothiophene to the donor compound is 1:2.5-3.

6. The method for preparing an aromatic diamine derivative according to claim 4, characterized in that: In step (2), a reaction system including an intermediate, zinc powder and ammonium chloride is constructed, and a reduction reaction is carried out under an inert gas atmosphere to prepare the aromatic diamine derivative.

7. The method for preparing an aromatic diamine derivative according to claim 6, characterized in that: The molar ratio of the intermediate, zinc powder and ammonium chloride is 1:30-35:10-12.

8. Use of the aromatic diamine derivative according to any one of claims 1 to 3 in the preparation of tumor treatment products, characterized in that: The tumor treatment product is an NO-activated tumor treatment product.

9. A method for improving the active oxygen generation capacity of aromatic diamine derivatives, characterized in that: include: The aromatic diamine derivative according to any one of claims 1 to 3 is subjected to a single electron transfer oxidation reaction with NO or an NO donor to enhance its ability to generate active oxygen.

10. The method for improving the active oxygen generating ability of aromatic diamine derivatives according to claim 9, characterized in that: The molar ratio of the aromatic diamine derivative to NO or NO donor is 1:0.1-1000, and the reaction occurs at a certain temperature or under white light irradiation.

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