An N-aryl ketone acid cyanine compound, its preparation method and application

Abstract

This invention belongs to the field of compound drug technology. It relates to an N-aryl ketone acid cyanine compound with the structure of general formula (I), obtained by a dehydration condensation reaction of a ketone acid compound of formula (II) and a diphenylamine derivative of formula (III) upon heating. The product structure has a donor-acceptor-donor conjugated structure. These compounds are structurally stable, possess good light-harvesting ability, and under laser irradiation, simultaneously exhibit reactive oxygen species generation and photothermal conversion capabilities, combining photodynamic and photothermal properties. They are non-toxic to cells, have good biocompatibility, and can be used as photosensitizers in the combined photothermal and photodynamic therapy of tumors.

Description

Technical Field

[0001] This invention belongs to the field of compound drug technology, and relates to an N-aryl ketocyanine compound, its preparation method and application. Background Technology

[0002] Cancer has long been a serious threat to human life and health. Traditional treatments, such as chemotherapy, radiotherapy, and surgery, have certain shortcomings, causing harm to the body while achieving therapeutic goals. Phototherapy, as a non-invasive treatment method, is more competitive compared to traditional methods. Phototherapy mainly includes photothermal therapy and photodynamic therapy. Photothermal therapy uses photosensitizers to convert light energy into heat energy, causing cancer cells to die from high temperatures. Photodynamic therapy, on the other hand, uses light energy to cause photosensitizers to undergo intersystem crossing from singlet to triplet states, producing highly cytotoxic reactive oxygen species, thereby inhibiting cancer cells. Phototherapy causes far less damage to surrounding healthy tissues than traditional treatments and has the advantages of low toxicity, high specificity, and no drug resistance. Currently, common photosensitizers are divided into inorganic and organic materials. Inorganic materials are difficult to metabolize in the human body and have poor biocompatibility, while organic materials can significantly overcome these shortcomings. Organic small-molecule photosensitizers have good stability and biocompatibility and are considered ideal materials for phototherapy. Therefore, the development of organic compounds with photothermal or photodynamic properties is of certain significance in cancer treatment drugs.

[0003] Photothermal therapy and photodynamic therapy exhibit compensatory effects in treatment, and combined therapy may achieve a synergistic therapeutic effect ("1+1>2"). Since the tumor microenvironment is hypoxic, the addition of photothermal effects can accelerate blood flow, thereby improving tissue oxygen supply and increasing the production of reactive oxygen species, which is beneficial for photodynamic therapy. Simultaneously, photodynamic effects can inhibit the expression of heat shock proteins, thereby reducing the heat resistance of tumor cells, which is also beneficial for photothermal therapy. Therefore, developing organic compounds with both photothermal and photodynamic effects as drugs has significant clinical application value in tumor treatment. Summary of the Invention

[0004] In view of this, the purpose of this invention is to provide an N-aryl ketone cyanine compound, its preparation method, and its applications. This compound has a stable structure, good light absorption capacity, and exhibits a significant temperature increase and the generation of reactive oxygen species after laser irradiation, while also possessing photodynamic and photothermal properties.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] 1. An N-aryl ketone acid cyanine compound having the molecular structure shown in the following general formula (I):

[0007] R1 and R2 are independently selected from hydrogen atoms, methyl groups, and methoxy groups, respectively.

[0008] Ethyl, isopropyl, tert-butyl, phenyl, or 1,1,2-triphenyl-vinyl.

[0009] Furthermore, N-aryl ketone cyanine compounds, the compounds represented by general formula (I) are compounds of formula (IV), (V), (VI), (VII), (VIII), (IX), (X), and (XI).

[0010]

[0011]

[0012] Furthermore, R1 is selected from methyl or methoxy.

[0013] The N-aryl ketocyanine compound of general formula (I) provided by this invention includes a ketocyanine group and a diphenylamine derivative group in its compound structure. The ketocyanine part is a strong electron-withdrawing group, which forms a conjugated system with the electron-donating diphenylamine derivative groups on both sides, and has good light absorption ability. Under light irradiation, the N-aryl ketocyanine compound converts light energy into heat energy and has good photothermal properties, which can be used for photothermal therapy of tumors. At the same time, after light irradiation, the N-aryl ketocyanine compound can also generate reactive oxygen species, which have good photodynamic properties and can also be used for photodynamic therapy of tumors.

[0014] 2. The preparation method of N-aryl ketone acid cyanine compounds specifically includes the following steps:

[0015] Compounds of formula (II) and (III) were added to an organic solvent in a molar ratio of 1:2 to 4, and a dehydration condensation reaction was carried out by heating to obtain the N-aryl ketone acid cyanine compound.

[0016] The compound of formula (II) has the following molecular structure:

[0017]

[0018] The compound of formula (III) has the following molecular structure:

[0019] R1 and R2 are independently selected from hydrogen atoms, methyl groups, methoxy groups, ethyl groups, and hydrogen atoms, respectively.

[0020] Isopropyl, tert-butyl, phenyl, or 1,1,2-triphenyl-vinyl.

[0021] In the further preparation method of N-aryl ketone cyanine compounds, a purification step is also included after the condensation reaction.

[0022] In the further preparation method of N-aryl ketocyanine compounds, the organic solvent is a mixture of toluene and n-butanol.

[0023] Preferably, the volume ratio of toluene to n-butanol is 1:1 to 3:1.

[0024] Preferably, the dehydration condensation reaction is carried out at a temperature of 100-130°C for 10-20 hours.

[0025] Preferably, the molar ratio of compound (II) and compound (III) is 1:2.

[0026] Preferably, the purification is performed by silica gel column chromatography, pulping and filtration, or / and thin-layer chromatography.

[0027] Preferably, the purification involves removing the solvent from the reaction solution, performing silica gel column chromatography on the solid substance, eluting with an organic solvent, collecting the eluent, removing the organic solvent from the eluent, pulping the obtained solid or preparing thin-layer chromatography, filtering or removing the solvent, and obtaining the N-aryl ketone cyanocyanate compound.

[0028] Preferably, the organic solvent is a mixture of dichloromethane and methanol.

[0029] Preferably, the eluent is a mixed solvent of dichloromethane and methanol with a volume ratio of 200:0.5-200:5.

[0030] Preferably, the solvent used during pulping is a mixture of ethyl acetate and methanol.

[0031] Preferably, the solvent used in preparing thin-layer chromatography is a mixture of dichloromethane and methanol, or a mixture of dichloromethane and ethyl acetate.

[0032] 3. It also provides the application of N-aryl ketocyanine compounds in the preparation of tumor therapeutic drugs.

[0033] Preferably, the drug is a photothermal photosensitizer;

[0034] Preferably, the drug is a photodynamic therapy photosensitizer;

[0035] Preferably, the drug is a photosensitizer for photothermal therapy combined with photodynamic therapy.

[0036] The beneficial effects of the present invention are as follows: The N-aryl ketocyanine compound with molecular structure such as general formula (I) provided by the present invention has a DAD (donor-acceptor-donor) conjugated structure constructed by ketocyanine group and diphenylamine derivative group. Experiments have shown that this structure not only has good light absorption capacity, but also has the ability to generate reactive oxygen species and photothermal conversion capacity under light conditions. It has both photodynamic and photothermal properties, is non-toxic to cells, has good biocompatibility, and can be used as a photosensitizer in the combined photothermal and photodynamic therapy of tumors. Attached Figure Description

[0037] To make the objectives, technical solutions, and beneficial effects of this invention clearer, the following figures are provided for illustration:

[0038] Figure 1 The absorption spectra of DMSO solutions of compounds IV, V, VI, and VII are shown.

[0039] Figure 2 The image shows the temperature change of DMSO solution of compound IV after irradiation with a 660nm laser at different concentrations and light powers.

[0040] Figure 3 The graph shows the photothermal stability of compound V in DMSO solution.

[0041] Figure 4 The graph shows the heating and cooling curves of the DMSO solution of compound VI, and the negative natural logarithm of time versus temperature during the natural cooling phase.

[0042] Figure 5 The graph shows the temperature changes of DMSO solution of compound VII after irradiation with a 660nm laser at different concentrations and light powers.

[0043] Figure 6 The graph shows the reactive oxygen species generation capacity of DMSO solutions containing compounds IV, V, VI, and VII.

[0044] Figure 7 The graph shows the dark toxicity and phototoxicity of compound IV on 4T1 cells. Detailed Implementation

[0045] Various exemplary embodiments of the present invention will now be described in detail with reference to the accompanying drawings. This detailed description should not be considered as a limitation of the invention, but rather as a more detailed description of certain aspects, characteristics, and embodiments of the invention. Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Unless otherwise specified, the raw materials, reagents, or apparatus used in the following examples are available from conventional commercial sources or can be obtained by existing known methods. Although only preferred methods and materials are described herein, any methods and materials similar to or equivalent to those described herein may be used in the implementation or testing of the invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail. The terms “comprising,” “including,” “having,” “containing,” etc., as used herein are open-ended terms, meaning that they include but are not limited to.

[0046] Example 1

[0047] An N-aryl ketone acid cyanine compound has the molecular structure shown in formula (IV):

[0048]

[0049] The preparation method of the above-mentioned N-aryl ketone acid cyanine compound of formula (IV) includes the following steps:

[0050] 1. Under argon atmosphere, 4.11 g (10 mmol) of 1-(4-bromophenyl)-1,2,2-tristyrene, 2.46 g (20 mmol) of 4-methoxyaniline, 39.00 μL (0.16 mmol) of tritert-butylphosphine, 128.00 mg (0.16 mmol) of tris(dibenzylacetone)dipalladium, and 1.92 g (20 mmol) of sodium tert-butoxide were added to a round-bottom flask, and anhydrous toluene was added as a solvent. The mixture was heated to reflux at 110°C for 24 hours, then cooled to room temperature, and the solvent was removed under reduced pressure. It was extracted with dichloromethane and water, and the organic layer was collected, dried with an appropriate amount of anhydrous sodium sulfate, concentrated, and further purified by column chromatography (eluent: petroleum ether: dichloromethane volume ratio = 3:1) to obtain 4-methoxy-N-(4-(1,2,2-tristyrene)phenyl)aniline (compound of formula (III-1)), a yellow powder solid (2.51 g, yield 55%). 1¹H NMR (400MHz, CDCl₃, ppm) δ 7.15–6.98 (m, 17H, Ar-H), 6.87–6.80 (m, 4H, Ar-H), 6.64 (d, J=8.4Hz, 2H, Ar-H), 3.78 (s, 3H, OCH₃). Compound (III-1) CAS: 2407147-57-1, structural formula as follows:

[0051]

[0052] 2. Weigh 907.16 mg (2 mmol) of the above-prepared 4-methoxy-N-(4-(1,2,2-tristyrene)phenyl)aniline and 142.07 mg (1 mmol) of 4,5-dihydroxycyclopent-4-ene-1,2,3-trione (compound of formula (II)) and add them to a two-necked flask. Add 6 mL of toluene and 6 mL of n-butanol, and heat under reflux at 120 °C for 12 hours. After the reaction is complete, stop heating, cool the reaction solution to room temperature, remove the solvent under reduced pressure, and pass the obtained solid by column chromatography (eluent:methanol volume ratio = 200:1) to obtain the crude product. The crude product is slurried using a mixed solvent of ethyl acetate and methanol (ethyl acetate:methanol volume ratio = 1:6), filtered and dried to obtain a brown powder solid (83.8 mg, 8%), thus preparing an N-aryl ketone cyanine compound with the molecular structure of formula (IV). 1 H NMR (400MHz, CDCl3, ppm) δ7.19–6.74 (m, 46H, Ar-H), 3.82 (s, 6H, OCH3). 13 C NMR (100MHz, CDCl3, ppm) δ179.0,159.6,143.4,143.2,143.0,142.2,139.8,131.5,131. 4,127.8,127.8,127.7,127.3,126.9,126.7,125.5,114.0,77.4,77.3,77.1,76.7,55.6. HRMS(ESI) + m / z:[M+H] + calcd.C 71 H 53 N2O5 + ,1013.3949; found,1013.3934.

[0053]

[0054] Example 2

[0055] An N-aryl ketone cyanine compound has the molecular structure shown in formula (V):

[0056]

[0057] The preparation method of the above-mentioned N-aryl ketone acid cyanine compound includes the following steps:

[0058] Bis(4-methoxyphenyl)amine: CAS No.: 101-70-2.

[0059] 458.56 mg (2 mmol) of bis(4-methoxyphenyl)amine and 142.07 mg (1 mmol) of 4,5-dihydroxycyclopent-4-ene-1,2,3-trione (compound of formula (II)) were weighed and added to a two-necked flask. 5 mL of toluene and 5 mL of n-butanol were added, and the mixture was heated under reflux at 120 °C for 12 hours. After the reaction was complete, heating was stopped, the reaction solution was cooled to room temperature, and the solvent was removed under reduced pressure. The obtained solid was subjected to column chromatography (eluent: dichloromethane:methanol, volume ratio = 40:1) to obtain the crude product. The crude product was recrystallized from dichloromethane and methanol, filtered, and dried to obtain a bright brown solid (84.7 mg, 15%), thus preparing an N-aryl ketone cyanine compound with the molecular structure of formula (V). 1 H NMR (400MHz, CDCl3, ppm) δ6.98 (dd, J=21.9, 8.5Hz, 8H, Ar-H), 6.85 (dd, J=14.9, 8.6Hz, 8H, Ar-H), 3.83 (d, J=4.9Hz, 12H, OCH3). 13 C NMR (100MHz, CDCl3, ppm) δ179.0,170.4,159.6,153.5,136.0,135.5,127.4,127.2,114.2,114.0,77.4,77.3,77.1,76.8,55.6,55.5. HRMS(ESI) + m / z:[M+H] + calcd.C 33 H 29 N2O7 + ,565.1969; found,565.1954.

[0060] Example 3

[0061] An N-aryl ketone acid cyanine compound has the molecular structure shown in formula (VI):

[0062]

[0063] The preparation method of the above-mentioned N-aryl ketone acid cyanine compound includes the following steps:

[0064] 4-Methoxy-N-(p-Tolyl)aniline CAS No.: 39253-43-5.

[0065] 1.28 g (6 mmol) of 4-methoxy-N-(p-tolyl)aniline and 0.43 g (3 mmol) of 4,5-dihydroxycyclopent-4-ene-1,2,3-trione (compound of formula (II)) were weighed and added to a two-necked flask. 15 mL of toluene and 15 mL of n-butanol were added, and the mixture was heated under reflux at 120 °C for 14 hours. After the reaction was completed, heating was stopped, the reaction solution was cooled to room temperature, and the solvent was removed under reduced pressure. The obtained solid was subjected to column chromatography (eluent:methanol, volume ratio = 150:1) to obtain the crude product. The crude product was washed with petroleum ether, then slurried with a mixture of ethyl acetate and methanol (ethyl acetate:methanol, volume ratio = 1:3), filtered, and dried to obtain a black solid (110 mg, 7%), thus preparing an N-aryl ketone cyanine compound with the molecular structure of formula (VI). 1 HNMR (400MHz, DMSO-d6, ppm) δ7.27–6.81(m,16H,Ar-H), 3.79(s,6H,-OCH3), 2.34(s,6H,-CH3). 13 C NMR (101MHz, CDCl3, ppm) δ179.0,159.7,140.0,138.8,129.6,127.5,126.0,125.8,114.2,114.0,55.5,21.4. HRMS(ESI) + m / z:[M+H] + calcd.C 33 H 29 N2O5 + ,533.2071found,533.2055.

[0066] Example 4

[0067] An N-aryl ketone cyanine compound has the molecular structure shown in formula (VII):

[0068]

[0069] The preparation method of the above-mentioned N-aryl ketone acid cyanine compound includes the following steps:

[0070] 4,4'-Dimethyldiphenylamine CAS No.: 620-93-9.

[0071] 1.18 g (6 mmol) of 4,4'-dimethyldiphenylamine and 0.43 g (3 mmol) of 4,5-dihydroxycyclopent-4-ene-1,2,3-trione (compound of formula (II)) were weighed and added to a two-necked flask. 15 mL of toluene and 15 mL of n-butanol were added, and the mixture was heated under reflux at 120 °C for 14 hours. After the reaction was completed, heating was stopped, the reaction solution was cooled to room temperature, and the solvent was removed under reduced pressure. The obtained solid was subjected to column chromatography (eluent:methanol volume ratio = 150:1) to obtain the crude product. The crude product was washed with petroleum ether and then slurried with a mixed solvent of ethyl acetate and methanol (ethyl acetate:methanol volume ratio = 1:5). The mixture was filtered and dried to obtain a black solid (99 mg, 7%), thus preparing an N-aryl ketone cyanine compound with the molecular structure of formula (VII). 1 HNMR (400MHz, DMSO-d6, ppm) δ7.18 (d, J = 7.8 Hz, 8H, Ar-H), 7.03 (d, J = 7.9 Hz, 8H, Ar-H), 2.34 (s, 12H, -CH3). 13 C NMR (101MHz, CDCl3, ppm) δ179.0,169.9,155.1,140.5,139.9,138.8,129.6,129.4,126.1,125.9,21.4. HRMS(ESI) + m / z:[M+H] + calcd.C 33 H 29 N2O3 + ,501.2173,found,501.2155.

[0072] Example 5

[0073] An N-aryl ketone acid cyanine compound has the molecular structure shown in formula (VIII):

[0074]

[0075] The preparation method of the above-mentioned N-aryl ketone acid cyanine compound includes the following steps:

[0076] 4-Methyldiphenylamine CAS No.: 620-84-8.

[0077] 1.10 g (6 mmol) of 4-methyldiphenylamine and 0.43 g (3 mmol) of 4,5-dihydroxycyclopent-4-ene-1,2,3-trione (compound of formula (II)) were weighed and added to a two-necked flask. 15 mL of toluene and 15 mL of n-butanol were added, and the mixture was heated under reflux at 120 °C for 12 hours. After the reaction was completed, heating was stopped, the reaction solution was cooled to room temperature, and the solvent was removed under reduced pressure. The obtained solid was subjected to column chromatography (eluent: dichloromethane:methanol, volume ratio = 400:1) to obtain the crude product. The crude product was further purified by thin-layer chromatography (developing solvent: dichloromethane:methanol, volume ratio = 200:1) to obtain an N-aryl ketone cyanine compound with the molecular structure of formula (VIII). 1 H NMR (400MHz, CDCl3, ppm) δ7.37–7.34(m,6H),7.10–6.86(m,12H),2.40–2.36(m,6H). HRMS(ESI) + m / z:[M+H] + calcd.C 31 H 25 N2O3 + ,473.1860,found:473.1850.

[0078] Example 6

[0079] An N-aryl ketone acid cyanine compound has the molecular structure shown in formula (IX):

[0080]

[0081] The preparation method of the above-mentioned N-aryl ketone acid cyanine compound includes the following steps:

[0082] N-Phenylen-4-benzidine CAS No.: 32228-99-2

[0083] 1.47 g (6 mmol) of N-phenyl-4-benzidine and 0.43 g (3 mmol) of 4,5-dihydroxycyclopent-4-ene-1,2,3-trione (compound of formula (II)) were weighed and added to a two-necked flask. 15 mL of toluene and 15 mL of n-butanol were added, and the mixture was heated under reflux at 120 °C for 12 hours. After the reaction was completed, heating was stopped, the reaction solution was cooled to room temperature, the solvent was removed under reduced pressure, and the obtained solid was purified by repeated preparative thin-layer chromatography (dichloromethane:ethyl acetate volume ratio = 30:1) to obtain an N-aryl ketone cyanine compound with the molecular structure of formula (IX). 1H NMR (400MHz, CDCl3, ppm) δ7.53–7.48(m,8H),7.37–7.29(m,12H),7.10–7.04(m,8H). HRMS(ESI) + m / z:[M+H] + calcd.C 41 H 29 N2O3 + ,597.2173,found:597.2155.

[0084] Example 7

[0085] An N-aryl ketone acid cyanine compound has the molecular structure shown in formula (X):

[0086]

[0087] The preparation method of the above-mentioned N-aryl ketone acid cyanine compound includes the following steps:

[0088] Bis(4-isopropylphenyl)amine CAS No.: 63451-41-2.

[0089] 0.76 g (3 mmol) of bis(4-isopropylphenyl)amine and 0.21 g (1.5 mmol) of 4,5-dihydroxycyclopent-4-ene-1,2,3-trione (compound of formula (II)) were weighed and added to a two-necked flask. 7.5 mL of toluene and 7.5 mL of n-butanol were added, and a condenser was connected. The mixture was heated under reflux at 120 °C for 12 hours. After the reaction was completed, heating was stopped, the reaction solution was cooled to room temperature, and the solvent was removed under reduced pressure. The obtained solid was subjected to column chromatography (eluent:methanol, volume ratio = 200:1) to obtain the crude product. The crude product was purified by repeated preparative thin-layer chromatography (dichloromethane:methanol, volume ratio = 100:1) to obtain an N-aryl ketone cyanine compound with the molecular structure of formula (X). 1 HNMR (400MHz, CDCl3, ppm) δ7.53–7.48(m,8H),7.37–7.29(m,12H),7.10–7.04(m,8H). HRMS(ESI) + m / z:[M+H] + calcd.C 41 H 29 N2O3 + ,613.3425,found:613.3411.

[0090] Example 8

[0091] An N-aryl ketone acid cyanine compound has the molecular structure shown in formula (XI):

[0092]

[0093] The preparation method of the above-mentioned N-aryl ketone acid cyanine compound includes the following steps:

[0094] Bis(4-tert-butylphenyl)amine CAS No. 4627-22-9.

[0095] 1.69 g (6 mmol) of bis(4-tert-butylphenyl)amine and 0.43 g (3 mmol) of 4,5-dihydroxycyclopent-4-ene-1,2,3-trione (compound of formula (II)) were weighed and added to a two-necked flask. 15 mL of toluene and 15 mL of n-butanol were added, and the flask was connected to a condenser and heated under reflux at 120 °C for 12 hours. After the reaction was completed, heating was stopped, the reaction solution was cooled to room temperature, and the solvent was removed under reduced pressure. The obtained solid was subjected to column chromatography (eluent: dichloromethane) to obtain the crude product. The crude product was purified by repeated preparative thin-layer chromatography (developing solvent: dichloromethane) to obtain an N-aryl ketone cyanine compound with the molecular structure of formula (XI).

[0096] 1 HNMR (400MHz, CDCl3) δ7.39–7.28(m,8H),7.03–6.92(m,8H),1.32–1.28(m,36H). HRMS(ESI) + m / z:[M+H] + calcd.C 45 H 53 N2O3 + ,669.4051,found:669.4035.

[0097] Photothermal properties of compounds IV, V, VI, and VII in Example 9

[0098] The temperature changes of the solutions were detected and the photothermal conversion efficiency of the compounds was calculated by varying the concentrations of solutions of compounds IV, V, VI, and VII and the laser power. Compounds IV, V, VI, and VII were prepared as stock solutions with a concentration of 1 mg / mL using DMSO, and then diluted with DMSO to the desired concentrations. Figure 1 The absorption spectra of DMSO solutions (20 μM) containing compounds IV, V, VI, and VII are shown. The temperature was increased by irradiation with a 660 nm laser, and real-time temperature changes were detected using a near-infrared imager. Figure 2 The image shows the temperature change of DMSO solution of compound IV after irradiation with a 660nm laser at different concentrations and light powers. Figure 3 The photothermal stability of compound V in DMSO solution was demonstrated. Figure 4The heating and cooling curves of a DMSO solution (50 mg / ml) of compound VI are shown, and the time versus temperature during the natural cooling phase exhibits a negative natural logarithmic relationship. Figure 5 The temperature changes of DMSO solution of compound VII after irradiation with a 660 nm laser at different concentrations and light powers are shown.

[0099] Tests showed that the temperature of systems containing compounds IV, V, VI, and VII increased with increasing irradiation time, solution concentration, and laser power. When the laser power was fixed at 1 W / cm², the temperature of the system increased further. 2 At a concentration of 7.8125 μg / mL, compound IV reached a system temperature of 60℃ with a photothermal conversion efficiency of 25%; compound V reached a system temperature of 76℃ with a photothermal conversion efficiency of 36%; compound VI reached a system temperature of 85℃ with a photothermal conversion efficiency of 36%; and compound VII reached a system temperature of 90℃ with a photothermal conversion efficiency of 32%. These results indicate that these compounds possess excellent photothermal conversion properties and can be used for photothermal therapy of tumors.

[0100] Photodynamic properties of compounds IV, V, VI, and VII in Example 10

[0101] 2',7'-dichlorofluorescein diacetate (DCFH), a probe for detecting reactive oxygen species, was added to solutions of compounds IV, V, VI, and VII. After irradiation with a 660 nm laser, changes in fluorescence intensity were detected; a larger change in fluorescence intensity indicated a stronger ability to generate reactive oxygen species. Compounds IV, V, VI, and VII were prepared into 100 μM analyte solutions using DMSO, and the DCFH probe was prepared into a 30 μM working solution using PBS buffer. The analyte solutions and working solutions were mixed, and a 100 mW / cm² laser was used. 2 Irradiation with a 660nm laser was performed, and the fluorescence intensity was recorded every 10 seconds. For example... Figure 6 As shown, compared with the blank control group, solutions of compounds IV, V, VI, and VII all generated reactive oxygen species, with compound IV exhibiting the strongest ability to generate reactive oxygen species.

[0102] Example 11: Dark toxicity and phototoxicity of compound IV

[0103] Compound IV was prepared into nanoparticles using a nanoprecipitation method to increase its water solubility. 4T1 cells were seeded into 96-well plates (1×10⁻⁶ cells / well). 4Cells were incubated at 37°C and 5% CO2 for 24 hours until adherence. The old culture medium was discarded, and compound IV nanoparticle solutions (500 μg / mL, 250 μg / mL, 125 μg / mL, 62.5 μg / mL, 31.25 μg / mL, 15.625 μg / mL) were prepared using serum-free medium. 100 μL was added to each well, arranged in rows as a group, with 6 replicates per group. The dark group was cultured for another 24 hours. The laser group, after 24 hours of drug addition, had its supernatant discarded, was washed with PBS until no residue remained, and then irradiated with a 660 nm laser (1.0 W / cm²). 2 After 10 min (1 min / well), add 100 μL of fresh serum-free culture medium to each well and continue culturing for 4 h. Cell viability was then measured using the standard MTT assay in both groups. The results are shown below. Figure 7 As shown. Figure 7 In Figure 'a', the effect of different concentrations of compound IV nanosolution on the viability of 4T1 cells under dark conditions is shown. Figure 7 Figure b shows the effect of different concentrations of compound IV nanosolution on the viability of 4T1 cells under light irradiation. Figure 7 Figure a shows that 4T1 cells maintained high viability even without laser irradiation within a concentration range of 15.625–500 μg / mL for the compound IV nanosolution. Even at a concentration as high as 500 μg / mL, the cell viability remained as high as 86%, indicating that the compound IV nanosolution possesses good biocompatibility. Figure 7 Figure b shows that under laser irradiation, cell viability decreases with increasing concentration of compound IV nanosolution. When the concentration of compound IV nanosolution is 500 μg / mL, cell viability is significantly inhibited, demonstrating that compound IV nanosolution possesses excellent tumor-killing ability.

[0104] Finally, it should be noted that the above description is merely a preferred embodiment of the present invention. Those skilled in the art, under the guidance of the present invention, may make various changes in form and detail without departing from the spirit and claims of the present invention, and all such changes fall within the scope defined by the claims of the present invention.

Claims

1. An N-aryl ketone acid cyanine compound, characterized in that, It has the molecular structure shown in the general formula (I): R1 and R2 are independently selected from methyl, methoxy, ethyl, isopropyl, tert-butyl or 1,1,2-triphenyl-vinyl.

2. The N-aryl ketone acid cyanine compound according to claim 1, characterized in that, R1 is selected from methyl or methoxy.

3. The method for preparing the N-aryl ketone cyanine compound according to claim 1, characterized in that, Includes the following steps: Compounds of formula (II) and (III) were added to an organic solvent in a molar ratio of 1:2 to 4, and a dehydration condensation reaction was carried out by heating to obtain the N-aryl ketone acid cyanine compound. The compound of formula (II) has the following molecular structure: ； The compound of formula (III) has the following molecular structure: R1 and R2 are independently selected from methyl, methoxy, ethyl, isopropyl, tert-butyl or 1,1,2-triphenyl-vinyl.

4. The method for preparing the N-aryl ketone acid cyanine compound according to claim 3, characterized in that, The condensation reaction is followed by a purification step.

5. The method for preparing the N-aryl ketone acid cyanine compound according to claim 3, characterized in that, The organic solvent is a mixture of toluene and n-butanol.

6. The method for preparing the N-aryl ketone acid cyanine compound according to claim 5, characterized in that, The volume ratio of toluene to n-butanol is 1:1 to 3:

1.

7. The method for preparing the N-aryl ketone cyanine compound according to claim 3, characterized in that, The dehydration condensation reaction is carried out at a temperature of 100-130℃ for 10-20 hours.

8. The method for preparing the N-aryl ketone cyanine compound according to claim 4, characterized in that, The purification is performed by silica gel column chromatography, pulping and filtration, or / and thin-layer chromatography.

9. The method for preparing the N-aryl ketone cyanine compound according to claim 4, characterized in that, The purification process involves removing the solvent from the reaction solution, subjecting the solid substance to silica gel column chromatography, eluting with an organic solvent, collecting the eluent, removing the organic solvent from the eluent, pulping the obtained solid or preparing thin-layer chromatography, filtering or removing the solvent, and then obtaining the N-aryl ketone cyanocyanate compound.

10. The use of the N-aryl ketone cyanine compound according to claim 1 or 2 in the preparation of photosensitizers, characterized in that, The photosensitizer is used for photodynamic therapy and / or photothermal therapy of tumors.

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