Highly conjugated photosensitizer, preparation method thereof and application of highly conjugated photosensitizer in photodynamic therapy

Abstract

The invention discloses a highly conjugated photosensitizer with efficient ROS (reactive oxygen species) generation capability and a preparation method thereof, the photosensitizer is prepared by taking halogenated BOPYIN as a raw material, catalyzing tetra (triphenylphosphine) palladium (0) and K2CO3 under the protection of N2 and coupling with 4-diphenylaminophenylboronic acid, the synthesis method is simple, separation and purification are convenient, and the yield is higher. An aromatic ring is introduced to a parent structure, so that an absorption spectrum is subjected to red shift and has relatively high stability. The compound has the characteristic of long wavelength absorption due to the expanded conjugated structure, and the optical characteristic enables the compound to be effectively applied to the field of photodynamic therapy.

Description

Technical Field

[0001] The present invention relates to the field of fine chemicals, and more specifically, to a highly conjugated photosensitizer with high-efficiency ROS generation ability and a preparation method thereof. Background Art

[0002] As an emerging tumor treatment method, photodynamic therapy (PDT) highly depends on the performance of photosensitizers. An ideal photosensitizer should have high-efficiency reactive oxygen species (ROS) generation ability, suitable light absorption characteristics, and good biocompatibility. However, existing photosensitizers still face many challenges in clinical applications. Although traditional porphyrin-based and phthalocyanine-based photosensitizers have been widely studied, due to their inherent molecular structure limitations, they often have problems such as insufficient ROS yield and poor photostability. Although metal complex photosensitizers developed in recent years have improved the ROS yield to a certain extent, they introduce potential metal toxicity risks.

[0003] With the in-depth study of organic photosensitizers, highly conjugated organic molecules show unique advantages due to their adjustable electronic structures and excellent photophysical properties. By expanding the π-conjugated system, such molecules can effectively enhance the light capture ability, and at the same time, reasonable molecular design can optimize the excited state energy transfer process. However, existing highly conjugated photosensitizers still have deficiencies such as cumbersome synthesis methods and low yields, which restrict their practical applications.

[0004] To address the above problems, the present invention has developed a novel highly conjugated photosensitizer YB-D and its efficient preparation method. This photosensitizer significantly improves the ROS generation efficiency through unique molecular design, and at the same time, its optimized synthesis process solves the problem of difficult balance between yield and purity in the prior art, providing a better choice for photodynamic therapy. Summary of the Invention

[0005] The main object of the present invention is to provide a highly conjugated photosensitizer with high-efficiency ROS generation ability and a preparation method thereof.

[0006] The technical solution of the present invention is as follows: A highly conjugated photosensitizer with high-efficiency ROS generation ability, the chemical structural formula of the photosensitizer is:

[0007] YB-D.

[0008] The preparation method of a highly conjugated photosensitizer with high-efficiency ROS generation ability, the method includes the following synthesis route:

[0009] YBYB-D The method includes the following steps: (1) Under the protection of an inert atmosphere, compound YB, 1,4-dioxane, and 4-diphenylaminophenylboronic acid were placed in a reaction vessel and magnetically stirred to form a homogeneous system. Subsequently, a catalyst, potassium carbonate, and deionized water were added in sequence. After replacing the reaction system with nitrogen, a coupling reaction was carried out within the temperature range from room temperature to reflux temperature to obtain a target reaction mixture. (2) The reaction mixture obtained in step (1) was washed with water, extracted with an organic solvent, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography to obtain the target product YB-D, whose structural characterization confirmed it to be a highly conjugated photosensitizer.

[0010] In the above step (1), the feeding ratio of compound YB, 4-diphenylaminophenylboronic acid, catalyst, and potassium carbonate was 1:1~8:0.01~0.1:2~5.

[0011] The catalyst includes one of tetrakis(triphenylphosphine)palladium(0), tris(dibenzylideneacetone)dipalladium(0), and bis(tri-tert-butylphosphine)palladium(0).

[0012] In the above step (1), the volume ratio of 1,4-dioxane to deionized water was 6~9:1.

[0013] In the above step (1), the feeding sequence was to first add compound YB, 1,4-dioxane, and 4-diphenylaminophenylboronic acid, and then add the catalyst and potassium carbonate after complete dissolution. This sequence can ensure the complete dissolution of the reactants and prevent the inactivation of the catalyst under alkaline conditions. Changing the feeding sequence may lead to the decomposition of the catalyst or side reactions of the substrate.

[0014] The heating reflux reaction temperature in the above step (1) was 30~90 °C, and the heating time was 1~5 hours.

[0015] In another aspect, the present invention relates to the use of the highly conjugated photosensitizer or the highly conjugated photosensitizer prepared by the above method in the preparation of a drug for photodynamic therapy of cancer tumor cells.

[0016] The YB-D combined medium group obtained by incubating the highly conjugated photosensitizer in the medium for 3 - 5 h.

[0017] The above highly conjugated photosensitizer or YB-D combined medium group generates reactive oxygen species (ROS) under irradiation with light at 600 - 700 nm, induces apoptosis of cancer cells, and realizes the treatment of tumor cells.

[0018] The cancer tumor cells include human cervical cancer cells, and the human cervical cancer cells include Hela cells.

[0019] The maximum absorption wavelength of the photosensitizer in dimethyl sulfoxide is 641 nm.

[0020] The beneficial effects of the present invention are as follows: (1) The present invention provides a highly conjugated photosensitizer based on halogenated BOPYIN and its preparation method. Through precise molecular design, this photosensitizer achieves high-efficiency ROS generation ability and excellent photostability. Under the irradiation of 600 - 700 nm (preferably 635 nm) laser, it shows significant photodynamic killing effect on Hela tumor cells. At the same time, it has extremely low toxicity to normal cells under dark conditions, with good biosafety and tumor-selective accumulation characteristics. This photosensitizer not only solves the problem that it is difficult to balance ROS production rate and biosafety in the prior art, but also the modifiable sites reserved in its molecular structure provide convenience for the subsequent development of a series of derivatives, showing important clinical application value and broad industrialization prospects in the field of tumor photodynamic therapy.

[0021] (2) The synthesis reaction conditions of the highly conjugated photosensitizer with high-efficiency ROS generation ability described in the present invention are easy to control. Its preparation method realizes the preparation of target products with high yield and high purity by optimizing reaction conditions. The technological process is simple and has industrialization advantages. Description of the Drawings

[0022] Figure 1 is the 1H NMR spectrum of compound YB-D obtained in Example 9.

[0023] Figure 2 is the single crystal diagram of compound YB-D obtained in Example 9.

[0024] Figure 3 is the UV absorption spectrum of compound YB-D obtained in Example 9.

[0025] Figure 4 is the cell live / dead staining image of compound YB-D obtained in Example 9.

[0026] Figure 5 is the detection image of the ROS generation ability of compound YB-D at the cell level obtained in Example 9. Detailed Embodiments

[0027] The following examples are used to further illustrate the present invention, but the scope required to be protected by the present invention is not limited to the scope described in the examples.

[0028] Example 1 In a 50 mL eggplant-shaped reaction flask, compound YB (403.97 mg, 1.0 mmol) and 1,4-dioxane (27.00 mL) were added. After stirring until completely dissolved, 4-diphenylaminophenylboronic acid (289.14 mg, 1.0 mmol), tetrakis(triphenylphosphine)palladium(0) (11.56 mg, 0.01 mmol), potassium carbonate (276.00 mg, 2.0 mmol) and deionized water (3.00 mL) were added successively. After the system was purged with nitrogen three times, it was stirred and reacted at 30 °C in an oil bath for 5 hours (the reaction was monitored by TLC until completion). After the reaction was completed, the reaction mixture was cooled to room temperature, washed with deionized water (3 × 20 mL), extracted with dichloromethane (3 × 30 mL), the organic phases were combined and dried over anhydrous sodium sulfate. After concentration under reduced pressure, it was purified by silica gel column chromatography (eluent: petroleum ether / dichloromethane = 5:1, v / v) to obtain the target product YB-D (210.14 mg, black solid), with a yield of 27%.

[0029]

[0030] YB-D Example 2 In a 50 mL eggplant-shaped reaction flask, compound YB (403.97 mg, 1.0 mmol) and 1,4-dioxane (27.00 mL) were added. After stirring until completely dissolved, 4-diphenylaminophenylboronic acid (1156.56 mg, 4.0 mmol), tetrakis(triphenylphosphine)palladium(0) (11.56 mg, 0.01 mmol), potassium carbonate (276.00 mg, 2.0 mmol) and deionized water (3.00 mL) were added successively. After the system was purged with nitrogen three times, it was stirred and reacted at 30 °C in an oil bath for 5 hours (the reaction was monitored by TLC until completion). After the reaction was completed, the reaction mixture was cooled to room temperature, washed with deionized water (3 × 20 mL), extracted with dichloromethane (3 × 30 mL), the organic phases were combined and dried over anhydrous sodium sulfate. After concentration under reduced pressure, it was purified by silica gel column chromatography (eluent: petroleum ether / dichloromethane = 5:1, v / v) to obtain the target product YB-D (264.63 mg, black solid), with a yield of 34%. When the amount of 4-diphenylaminophenylboronic acid was increased by 3.0 mmol compared with Example 1, the yield of product YB-D increased by 7%.

[0031]

[0032] YB-D Example 3 In a 50 mL eggplant-shaped reaction flask, compound YB (403.97 mg, 1.0 mmol) and 1,4-dioxane (27.00 mL) were added. After stirring until completely dissolved, 4-diphenylaminophenylboronic acid (2313.12 mg, 8.0 mmol), tetrakis(triphenylphosphine)palladium(0) (11.56 mg, 0.01 mmol), potassium carbonate (276.00 mg, 2.0 mmol), and deionized water (3.00 mL) were added successively. After the system was purged with nitrogen three times, it was stirred and reacted for 5 hours under an oil bath condition at 30 °C (the reaction was monitored by TLC until completion). After the reaction was completed, the reaction mixture was cooled to room temperature, washed with deionized water (3 × 20 mL), extracted with dichloromethane (3 × 30 mL), the organic phases were combined and dried over anhydrous sodium sulfate. After concentration under reduced pressure, it was purified by silica gel column chromatography (eluent: petroleum ether / dichloromethane = 5:1, v / v) to obtain the target product YB-D (365.81 mg, black solid), with a yield of 47%. When the amount of 4-diphenylaminophenylboronic acid was increased by 4.0 mmol compared to Example 2, the yield of product YB-D increased by 13%.

[0033]

[0034] YB-D Example 4 In a 50 mL eggplant-shaped reaction flask, compound YB (403.97 mg, 1.0 mmol) and 1,4-dioxane (27.00 mL) were added. After stirring until completely dissolved, 4-diphenylaminophenylboronic acid (2313.12 mg, 8.0 mmol), tetrakis(triphenylphosphine)palladium(0) (11.56 mg, 0.01 mmol), potassium carbonate (276.00 mg, 2.0 mmol), and deionized water (3.00 mL) were added successively. After the system was purged with nitrogen three times, it was stirred and reacted for 4 hours under an oil bath condition at 60 °C (the reaction was monitored by TLC until completion). After the reaction was completed, the reaction mixture was cooled to room temperature, washed with deionized water (3 × 20 mL), extracted with dichloromethane (3 × 30 mL), the organic phases were combined and dried over anhydrous sodium sulfate. After concentration under reduced pressure, it was purified by silica gel column chromatography (eluent: petroleum ether / dichloromethane = 5:1, v / v) to obtain the target product YB-D (381.38 mg, black solid), with a yield of 49%. When the reaction temperature was increased by 30 °C compared to Example 3, the yield of product YB-D increased by 2%, and the reaction time was reduced by 1 hour.

[0035]

[0036] YB-D Example 5 In a 50 mL eggplant-shaped reaction flask, compound YB (403.97 mg, 1.0 mmol) and 1,4-dioxane (27.00 mL) were added. After stirring until completely dissolved, 4-diphenylaminophenylboronic acid (2313.12 mg, 8.0 mmol), tetrakis(triphenylphosphine)palladium(0) (11.56 mg, 0.01 mmol), potassium carbonate (276.00 mg, 2.0 mmol), and deionized water (3.00 mL) were added in sequence. After the system was purged with nitrogen three times, it was stirred and reacted in an oil bath at 90 °C for 2 hours (the reaction was monitored by TLC until completion). After the reaction was completed, the reaction mixture was cooled to room temperature, washed with deionized water (3 × 20 mL), extracted with dichloromethane (3 × 30 mL), and the combined organic phases were dried over anhydrous sodium sulfate. After concentration under reduced pressure, it was purified by silica gel column chromatography (eluent: petroleum ether / dichloromethane = 5:1, v / v) to obtain the target product YB-D (428.07 mg, black solid), with a yield of 55%. When the reaction temperature was increased by 30 °C compared to Example 4, the yield of product YB-D increased by 6%, and the reaction time was reduced by 2 hours.

[0037]

[0038] YB-D Example 6 In a 50 mL eggplant-shaped reaction flask, compound YB (403.97 mg, 1.0 mmol) and 1,4-dioxane (27.00 mL) were added. After stirring until completely dissolved, 4-diphenylaminophenylboronic acid (2313.12 mg, 8.0 mmol), tetrakis(triphenylphosphine)palladium(0) (34.68 mg, 0.03 mmol), potassium carbonate (276.00 mg, 2.0 mmol), and deionized water (3.00 mL) were added in sequence. After the system was purged with nitrogen three times, it was stirred and reacted in an oil bath at 90 °C for 2 hours (the reaction was monitored by TLC until completion). After the reaction was completed, the reaction mixture was cooled to room temperature, washed with deionized water (3 × 20 mL), extracted with dichloromethane (3 × 30 mL), and the combined organic phases were dried over anhydrous sodium sulfate. After concentration under reduced pressure, it was purified by silica gel column chromatography (eluent: petroleum ether / dichloromethane = 5:1, v / v) to obtain the target product YB-D (490.34 mg, black solid), with a yield of 63%. When the amount of tetrakis(triphenylphosphine)palladium(0) was increased by 0.02 mmol compared to Example 5, the yield of product YB-D increased by 8%.

[0039]

[0040] YB-D Example 7 In a 50 mL eggplant-shaped reaction flask, compound YB (403.97 mg, 1.0 mmol) and 1,4-dioxane (27.00 mL) were added. After stirring until completely dissolved, 4-diphenylaminophenylboronic acid (2313.12 mg, 8.0 mmol), tetrakis(triphenylphosphine)palladium(0) (57.80 mg, 0.05 mmol), potassium carbonate (276.00 mg, 2.0 mmol), and deionized water (3.00 mL) were added successively. After the system was purged with nitrogen three times, it was stirred and reacted in an oil bath at 90 °C for 2 hours (the reaction was monitored by TLC until completion). After the reaction was completed, the reaction mixture was cooled to room temperature, washed with deionized water (3 × 20 mL), extracted with dichloromethane (3 × 30 mL), and the organic phases were combined and dried over anhydrous sodium sulfate. After concentration under reduced pressure, it was purified by silica gel column chromatography (eluent: petroleum ether / dichloromethane = 5:1, v / v) to obtain the target product YB-D (505.90 mg, black solid), with a yield of 65%. When the amount of tetrakis(triphenylphosphine)palladium(0) was increased by 0.02 mmol compared to Example 6, the yield of product YB-D increased by 2%.

[0041]

[0042] YB-D Example 8 In a 50 mL eggplant-shaped reaction flask, compound YB (403.97 mg, 1.0 mmol) and 1,4-dioxane (27.00 mL) were added. After stirring until completely dissolved, 4-diphenylaminophenylboronic acid (2313.12 mg, 8.0 mmol), tetrakis(triphenylphosphine)palladium(0) (57.80 mg, 0.05 mmol), potassium carbonate (552.00 mg, 4.0 mmol), and deionized water (3.00 mL) were added successively. After the system was purged with nitrogen three times, it was stirred and reacted in an oil bath at 90 °C for 2 hours (the reaction was monitored by TLC until completion). After the reaction was completed, the reaction mixture was cooled to room temperature, washed with deionized water (3 × 20 mL), extracted with dichloromethane (3 × 30 mL), and the organic phases were combined and dried over anhydrous sodium sulfate. After concentration under reduced pressure, it was purified by silica gel column chromatography (eluent: petroleum ether / dichloromethane = 5:1, v / v) to obtain the target product YB-D (560.38 mg, black solid), with a yield of 72%. When the amount of potassium carbonate was increased by 2 mmol compared to Example 7, the yield of product YB-D increased by 7%.

[0043]

[0044] YB-D Example 9 In a 50 mL eggplant-shaped reaction flask, compound YB (403.97 mg, 1.0 mmol) and 1,4-dioxane (27.00 mL) were added. After stirring until completely dissolved, 4-diphenylaminophenylboronic acid (2313.12 mg, 8.0 mmol), tetrakis(triphenylphosphine)palladium(0) (57.80 mg, 0.05 mmol), potassium carbonate (690.00 mg, 5.0 mmol) and deionized water (3.00 mL) were added successively. After the system was purged with nitrogen three times, it was stirred and reacted at 90 °C in an oil bath for 2 hours (the reaction was monitored by TLC until complete). After the reaction was completed, the reaction mixture was cooled to room temperature, washed with deionized water (3 × 20 mL), extracted with dichloromethane (3 × 30 mL), and the organic phases were combined and dried over anhydrous sodium sulfate. After concentration under reduced pressure, it was purified by silica gel column chromatography (eluent: petroleum ether / dichloromethane = 5:1, v / v) to obtain the target product YB-D (575.95 mg, black solid), with a yield of 74%. When the amount of potassium carbonate was increased by 1.0 mmol compared to Example 8, the yield of product YB-D increased by 2%.

[0045] Take the black solid YB-D (7.78 mg, 0.01 mmol) and dissolve it in 1 mL of dichloromethane to prepare a stock solution. Take 3 μL of the stock solution and add it to 3 mL of toluene, dichloromethane, ethyl acetate, acetone, methanol, and dimethyl sulfoxide respectively to measure the absorption wavelength of this compound (see Figure 3 ). This compound has a relatively long absorption wavelength and has a maximum absorption wavelength (651 nm) in toluene solvent.

[0046]

[0047] YB-D Example 10 In a 50 mL eggplant-shaped reaction flask, compound YB (403.97 mg, 1.0 mmol) and 1,4-dioxane (27.00 mL) were added. After stirring until completely dissolved, 4-diphenylaminophenylboronic acid (2313.12 mg, 8.0 mmol), tris(dibenzylideneacetone)dipalladium(0) (45.79 mg, 0.05 mmol), potassium carbonate (690.00 mg, 5.0 mmol) and deionized water (3.00 mL) were added successively. After the system was purged with nitrogen three times, the reaction was stirred at 90 °C in an oil bath for 2 hours (monitored by TLC until the reaction was complete). After the reaction was completed, the reaction mixture was cooled to room temperature, washed with deionized water (3 × 20 mL), extracted with dichloromethane (3 × 30 mL), the organic phases were combined and dried over anhydrous sodium sulfate. After concentration under reduced pressure, purification by silica gel column chromatography was carried out (eluent: petroleum ether / dichloromethane = 5:1, v / v) to obtain the target product YB-D (575.95 mg, black solid), with a yield of 72%. When the catalyst was changed from tetrakis(triphenylphosphine)palladium(0) in Example 9 to tris(dibenzylideneacetone)dipalladium(0), the yield of product YB-D decreased by 2%.

[0048] Example 11 In a 50 mL eggplant-shaped reaction flask, compound YB (403.97 mg, 1.0 mmol) and 1,4-dioxane (27.00 mL) were added. After stirring until completely dissolved, 4-diphenylaminophenylboronic acid (2313.12 mg, 8.0 mmol), bis(tri-tert-butylphosphine)palladium(0) (45.79 mg, 0.05 mmol), potassium carbonate (690.00 mg, 5.0 mmol) and deionized water (3.00 mL) were added successively. After the system was purged with nitrogen three times, the reaction was stirred at 90 °C in an oil bath for 2 hours (monitored by TLC until the reaction was complete). After the reaction was completed, the reaction mixture was cooled to room temperature, washed with deionized water (3 × 20 mL), extracted with dichloromethane (3 × 30 mL), the organic phases were combined and dried over anhydrous sodium sulfate. After concentration under reduced pressure, purification by silica gel column chromatography was carried out (eluent: petroleum ether / dichloromethane = 5:1, v / v) to obtain the target product YB-D (575.95 mg, black solid), with a yield of 70%. When the catalyst was changed from tetrakis(triphenylphosphine)palladium(0) in Example 9 to bis(tri-tert-butylphosphine)palladium(0), the yield of product YB-D decreased by 4%.

[0049] Example 12 Cell Viability and Cytotoxicity Staining Assay of Compound YB-D The cell viability and cytotoxicity staining assay was performed using the Hela cell line. Cells in good growth state were seeded at a density of 1.0×10 per well 5Cells were seeded at a density of [number of cells] per well in a 6-well cell culture plate (Corning Costar) and incubated overnight in a 37°C, 5% CO₂ incubator. Four groups of treatments were set up in the experiment: (1) control group (fresh medium only for culturing Hela cells); (2) light-only group (635 nm, 1.0 W / cm 2 ); (3) YB-D-only treatment group (medium containing YB-D); (4) YB-D combined with light treatment group. After changing the corresponding medium, incubation was continued for 4 hours.

[0050] Subsequently, the cells in each group were stained with 10 μL of Calein-AM (1.0 mM, for live cell staining) and 10 μL of PI (1.0 mM, for dead cell staining). Among them, the cells in the second and fourth groups were irradiated with a 635 nm laser (1.0 W / cm 2 ) after staining. After all groups were incubated for an additional 30 minutes, they were observed and photographed using a fluorescence microscope (Olympus, BX51). The experimental results showed that the cell survival rate was the highest in the control group; a small number of cell deaths occurred in the light-only group; partial cell deaths occurred in the YB-D-only treatment group; while in the YB-D combined with light treatment group, almost all cancer cells were killed, indicating that YB-D has a significant photodynamic therapy effect under the condition of 635 nm laser irradiation.

[0051] Example 13 Detection experiment of the ability of compound YB-D to generate ROS at the cellular level Hela cells (ATCC CCL-2) in the logarithmic growth phase were digested with 0.25% trypsin-EDTA and seeded at a density of 1.0×10 5 cells per well in a 6-well cell culture plate (Corning Costar). 2 mL of DMEM high-glucose medium (HyClone) containing 10% fetal bovine serum (Gibco) was added to each well. The cells were incubated overnight in a cell culture incubator (Thermo Scientific) at 37°C, 5% CO₂, and saturated humidity. In the experimental group, complete medium containing 5 μM YB-D (medium with YB-D added) was added, and in the control group, an equal volume of DMSO (final concentration <0.1%) was added. After continuing to incubate for 4 hours, the medium was aspirated, and a working solution of 10 μM DCFH-DA (Sigma-Aldrich, dissolved in serum-free medium) was added, and the cells were incubated at 37°C in the dark for 30 minutes. They were gently washed 3 times with pre-cooled PBS (pH 7.4) for 5 minutes each time to thoroughly remove extracellular probes.

[0052] A 635 nm near-infrared laser (Beijing Hi-Tech Optoelectronic, power density 1.0 W / cm 2, the light spot with a diameter of 3 cm was perpendicularly irradiated on the cells for 15 minutes at an irradiation distance of 10 cm. Immediately after the light irradiation, 4% paraformaldehyde was added for fixation for 15 minutes. After washing with PBS, an anti-fluorescence quenching mounting medium (containing 1 μg / mL DAPI, Beyotime) was added for mounting.

[0053] Observation was carried out using a fluorescence microscope (Olympus BX51, equipped with a DP72 digital camera). The U-MNIBA filter set (excitation wavelength 470 - 495 nm, emission wavelength 510 - 550 nm) was used to detect DCFH-DA fluorescence (green), and the U-MWU filter set (excitation wavelength 330 - 385 nm, emission wavelength 420 nm) was used to detect DAPI (blue). It was observed that the number of cells showing green coloration was relatively large, indicating that the photosensitizer had a strong ability to produce reactive oxygen species (ROS).

Claims

1. A highly conjugated photosensitizer, characterized in that, The chemical structural formula of the photosensitizer is as follows: YB-D.

2. The preparation method of the highly conjugated photosensitizer according to claim 1, characterized in that, The method includes the following synthesis route: YBYB-D (1) Under the protection of an inert atmosphere, compound YB, 1,4-dioxane, and 4-diphenylaminophenylboronic acid are placed in a reaction vessel and stirred to form a homogeneous system; subsequently, a catalyst, potassium carbonate, and deionized water are added in sequence. After the reaction system is replaced with nitrogen, a coupling reaction is carried out within the temperature range from room temperature to reflux temperature to obtain a target reaction mixture; (2) The reaction mixture obtained in step (1) is washed with water, extracted with an organic solvent, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and then purified by column chromatography to obtain the target product YB-D.

3. The preparation method according to claim 2, wherein, In step (1) described above, the feeding ratio of compound YB, 4-diphenylaminophenylboronic acid, catalyst, and potassium carbonate is 1:1~8:0.01~0.1:2~5.

4. The preparation method according to claim 2, characterized in that, The catalyst described in step (1) includes one of tetrakis(triphenylphosphine)palladium(0), tris(dibenzylideneacetone)dipalladium(0), and bis(tri-tert-butylphosphine)palladium(0).

5. The preparation method according to claim 2, wherein The heating temperature in step (1) is 30~90 °C, and the heating time is 1~5 hours.

6. Use of the highly conjugated photosensitizer according to claim 1 or the highly conjugated photosensitizer prepared by the method according to any one of claims 2-6 in the preparation of a drug for photodynamic therapy of cancer tumor cells.

7. The use according to claim 6, wherein The YB-D combined culture medium group obtained after incubating the highly conjugated photosensitizer in the culture medium for 3-5 h.

8. The use according to claim 7, characterized in that, The highly conjugated photosensitizer or the YB-D combined culture medium group generates reactive oxygen species (ROS) under irradiation with light of 600-700 nm, induces apoptosis of cancer cells, and realizes the treatment of tumor cells.

9. The use according to claim 8, characterized in that, The cancer tumor cells include human cervical cancer cells, and the human cervical cancer cells include Hela cells.

10. The use according to claim 9, characterized in that, The absorption wavelength of the photosensitizer is 641 nm.

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