Anthraquinone and anthracene compound meso-substituted cyanine dye and preparation method and application thereof

Abstract

The present invention discloses an anthraquinone and anthracene compound meso-substituted cyanine dye, its preparation method, and application. The anthraquinone and anthracene compound meso-substituted cyanine dye is prepared by meso-substituting a heptamethine cyanine dye with an anthraquinone or anthracene compound. The substituent groups regulate the fluorescence emission and heat release pathways of the dye, enhancing the photothermal effect of the dye molecule and enabling photoacoustic imaging. Furthermore, its excellent biocompatibility and low cytotoxicity make it suitable for use in the biological and medical fields.

Description

Technical Field

[0001] The present invention relates to the technical field of organic dyes, and in particular to anthraquinone and anthracene compound meso-substituted cyanine dye, and a preparation method and application thereof. Background Art

[0002] Due to its high morbidity and mortality, cancer has become one of the leading causes of harm to human life. Traditional treatments, including chemotherapy, radiotherapy, and surgery, remain the most commonly used clinical approaches. However, these approaches are extremely harmful to the human body and can produce serious side effects. Consequently, less invasive and more specific tumor-targeted treatments have been developed. Combined with imaging methods such as fluorescence imaging and photoacoustic imaging (PA), photodynamic therapy (PDT) and photothermal therapy (PTT) have attracted widespread attention in the fields of cancer monitoring and treatment.

[0003] Cyanine dyes are an important class of small organic molecule dyes. Compared to other organic dyes, they possess high molar extinction coefficients, excellent lipophilicity and hydrophilicity, low toxicity, and good biocompatibility. They also possess numerous modification sites and controllable excitation and emission wavelengths. Consequently, cyanine dyes have a broad range of applications, including bioimaging and therapeutic research.

[0004] Among them, indocyanine green (ICG) has been approved by the U.S. Food and Drug Administration (FDA) and is widely used in tumor imaging and phototherapy. However, these heptamethine cyanine dye-based reagents have weak photodynamic or photothermal conversion capabilities and poor therapeutic effects, and further improvement is still needed. Summary of the Invention

[0005] The present invention addresses the above issues and designs a novel anthraquinone and anthracene compound meso-substituted cyanine dye, as well as its preparation method and application. The technical means employed in the present invention are as follows:

[0006] An anthraquinone and anthracene compound meso-substituted cyanine dye having a structure as shown in general formula I:

[0007]

[0008] In formula I, R1 is selected from a group of the following structural formula

[0009] Preferred

[0010]

[0011] R2 is selected from any one of an alkyl group having 1 to 5 carbon atoms, a hydroxyl group having 1 to 5 carbon atoms, a carboxyalkyl group having 1 to 5 carbon atoms, an alkylsulfonate or alkylsulfonate having 1 to 5 carbon atoms, an aryl group, an arylsulfonate or arylsulfonate, preferably an alkyl group having 1 to 5 carbon atoms or an alkylsulfonate or alkylsulfonate having 1 to 5 carbon atoms;

[0012] R3 is selected from hydrogen, halogen, carboxyl, sulfonic acid or sulfonate, preferably hydrogen or halogen, more preferably hydrogen or bromine.

[0013] The anthraquinone and anthracene compound meso-substituted cyanine dyes may specifically have one of the following molecular structures:

[0014]

[0015] A method for preparing the anthraquinone and anthracene compound meso-substituted cyanine dyes of the present invention comprises the following steps:

[0016]

[0017] S1: reacting a 2,3,3-trimethylindole Y-1 containing an R3 substitution with an N-alkylating agent in a first organic solvent at a reaction temperature of 60-100° C. for 12-24 hours to obtain a compound Y-2 containing an N-R2 substituted side chain; the N-alkylating agent is selected from an alkane or a halogenated alkane containing an R2 substitution;

[0018] S2: Compound Y-2 prepared in step S1, 2-chloro-3-(hydroxymethylene)-1-cyclohexene-1-carbaldehyde, sodium acetate and a second organic solvent are mixed and reacted at 60-130° C. for 1-24 hours to obtain an intermediate product Y-3;

[0019] S3: The intermediate product Y-3 obtained in step S2, the compound containing R1, the first compound, and the third organic solvent are uniformly mixed and reacted at 25-80° C. for 2-8 hours to obtain anthraquinone and anthracene compound meso-substituted cyanine dye I, wherein the first compound is sodium hydride, triethylamine or potassium carbonate.

[0020] Furthermore, in step S1, the molar ratio of the R3-substituted 2,3,3-trimethylindole Y-1 to the N-alkylating agent is 1:(1-5), and the first organic solvent is acetone, ethanol, acetonitrile, benzene, toluene or o-dichlorobenzene; in step S2, the molar ratio of compound Y-2, 2-chloro-3-(hydroxymethylene)-1-cyclohexene-1-carboxaldehyde, and sodium acetate is (2-2.4):1:(2-2.5), and the second organic solvent is benzene, toluene, o-dichlorobenzene, methanol, ethanol, propanol, butanol, acetic acid or acetic anhydride; in step S3, the molar ratio of compound Y-3, the compound containing R1, and the first compound is 1:(1-2):(1.2-4), and the third organic solvent is dichloromethane, N,N-dimethylformamide, acetonitrile, toluene or o-dichlorobenzene, and the compound containing R1 is preferably 2-hydroxyanthraquinone, 2-hydroxyanthracene or 2-aminoanthraquinone.

[0021] A use of the anthraquinone and anthracene compound meso-substituted cyanine dyes of the present invention in the preparation of in vivo imaging preparations or photothermal therapeutic drugs, especially tumor therapeutic drugs.

[0022] Compared with the prior art, the anthraquinone and anthracene compound meso-substituted cyanine dyes and their preparation methods and applications described in the present invention have the following beneficial effects:

[0023] First, the anthraquinone and anthracene compounds of the present invention are meso-substituted cyanine dyes, and photoacoustic imaging and photothermal effects are achieved by introducing anthraquinone and anthracene compounds into the meso position of the heptamethine cyanine dye.

[0024] Second, the dyes prepared using the preparation method of the present application have near-infrared light absorption. Compared with the unsubstituted compounds, the fluorescence of this type of dye is quenched, and its photothermal conversion ability is greatly improved. It can effectively kill tumor cells under light, which indicates that this type of dye can be well used in the fields of deep in vivo photoacoustic imaging and tumor treatment.

[0025] Third, the dyes described in the present invention have good biocompatibility. After culturing 4T1 cells with a maximum concentration of 50 μmol / L of the compound for 24 hours, the cells still showed a good survival rate, indicating that the anthraquinone and anthracene compound substituted cyanine dyes provided in this application have very good biocompatibility and will not produce toxic side effects on cells within the working concentration range. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 1 is the normalized absorption spectrum of Compound 1 and Compound 2 in methanol in the examples of the present invention.

[0027] Figure 2 1 is the normalized fluorescence emission spectrum of Compound 1 and Compound 2 in methanol in the examples of the present invention.

[0028] Figure 3 This is a photothermal effect diagram of compound 1 and compound 2 in the examples of the present invention.

[0029] Figure 4 This is an MTT test graph of compound 1 in an example of the present invention under no light and light conditions.

[0030] Figure 5 a and Figure 5 b is the photoacoustic imaging of 4T1 tumor-bearing nude mice without and with injection of Compound 1 in the example of the present invention. DETAILED DESCRIPTION

[0031] The present invention is described in further detail below.

[0032] Unless otherwise specified, the terms used in the present invention have the following meanings.

[0033] The term "halogen" as used herein includes fluorine, chlorine, bromine and iodine.

[0034] The term "MTT" as used in the present invention refers to a method for detecting cell survival and growth.

[0035] The term "alkyl group" used in the present invention includes straight-chain alkyl groups and branched-chain alkyl groups.

[0036] The instruments and equipment used in the examples are:

[0037] In the column chromatography process of the present invention, column chromatography silica gel with 200-300 mesh and 100-200 mesh purchased from Qingdao Meigao Group Co., Ltd. and analytical pure quartz sand with 20-40 mesh purchased from Tianda Chemical Reagent Factory are used.

[0038] During the detection of the compounds, nuclear magnetic resonance hydrogen spectrum was detected using Bruker AvanceIII500 produced by Bruker Company of the United States.

[0039] The absorption and emission spectra and photostability of the dyes were measured using an Agilent Cary 60 UV-visible spectrophotometer and a Cary Eclipse fluorescence spectrophotometer. The absolute fluorescence quantum yield of the dyes was measured using a C11347 absolute fluorescence quantum yield instrument from Hamamatsu Photonics Trading (China) Co., Ltd.

[0040] The cytotoxicity test was measured using Varioskan LUX Multimode Microplate Reader from Thermofisher, USA.

[0041] Photoacoustic imaging was monitored by an InVision 128 MSOT system (iThera Medical, Germany).

[0042] Animals and tumor models All animal experiments involved in this work were approved by the Animal Care and Use Committee of Dalian Medical University.

[0043] Example 1 Preparation of Compound 1

[0044]

[0045] Synthesis route of compound 1:

[0046] S1: 2,3,3-Trimethyl-3H-indole (2 g, 12.56 mmol) and 1,3-propane sultone (1.53 g, 12.56 mmol) were added to a reaction bottle containing 10 mL of acetonitrile and refluxed under nitrogen for 24 h. After the reaction, the mixture was cooled to room temperature and then washed with 50 mL of ethyl acetate to obtain the intermediate 1-1 (1.15 g, 4.09 mmol, Y = 65.20%) as a purple solid powder.

[0047] S2: The intermediate 1-1 (500 mg, 1.77 mmol) obtained in step S1, 2-chloro-3-(hydroxymethylene)-1-cyclohexene-1-carbaldehyde (0.14 g, 0.81 mmol) and sodium acetate (0.16 g, 2 mmol) were added to 10 mL of acetic anhydride solution and refluxed at 110°C for 4 h. After the reaction, the solid was slurried in ethyl acetate and used directly in the next step (0.28 g, 0.4 mmol, Y = 48.32%).

[0048] S3: 2-Hydroxyanthraquinone (186.51 mg, 0.83 mmol), sodium hydride (19.96 mg, 0.83 mmol), and the intermediate product 1-2 (0.5 g, 0.69 mmol) obtained in step S2 were mixed evenly in 10 ml of N,N-dimethylformamide, and the mixture was reacted at 90°C for 6 h. After the reaction, the solvent was removed by rotary evaporation and purified by HPLC preparative chromatography to obtain compound 1 (0.08 g, 0.092 mmol, Y = 13.0%).

[0049] use 1 It was characterized by H NMR.

[0050] 1H NMR(400MHz, Methanol-d4)δ8.42(d,J=8.7Hz,1H),8.35–8.25(m,2H),7.97(s,1H),7 .95–7.85(m,4H),7.71(dd,J=8.7,2.7Hz,1H),7.37(dd,J=6.7,3.3Hz,6H),7.19(dq,J =10.3,3.8,2.4Hz,2H),6.42(d,J=14.2Hz,2H),4.35(t,J=7.7Hz,4H),2.96(t,J=6.7H z,4H),2.88(t,J=6.1Hz,4H),2.23(p,J=6.9Hz,4H),2.15–2.08(m,2H),1.36(s,12H).

[0051] Example 2 Preparation of Compound 2

[0052] Synthesis route of compound 2:

[0053]

[0054] S1: 2,3,3-Trimethyl-3H-indole (2 g, 12.56 mmol) and 1,3-propane sultone (1.53 g, 12.56 mmol) were added to a reaction bottle containing 10 mL of acetonitrile and refluxed under nitrogen for 24 h. After the reaction, the mixture was cooled to room temperature and then washed with 50 mL of ethyl acetate to obtain the intermediate 1-1 (1.15 g, 4.09 mmol, Y = 65.20%) as a purple solid powder.

[0055] S2: The intermediate 1-1 (500 mg, 1.77 mmol) obtained in step S1, 2-chloro-3-(hydroxymethylene)-1-cyclohexene-1-carbaldehyde (0.14 g, 0.81 mmol) and sodium acetate (0.16 g, 2 mmol) were added to 10 mL of acetic anhydride solution and refluxed at 110°C for 4 h. After the reaction, the solid was slurried in ethyl acetate and used directly in the next step (0.28 g, 0.4 mmol, Y = 48.32%).

[0056] S3: 2-Hydroxyanthracene (161.60 mg, 0.83 mmol), potassium carbonate (383.20 mg, 2.77 mmol), and the intermediate product 1-2 (0.5 g, 0.69 mmol) obtained in step S2 were mixed evenly in 10 ml of acetonitrile, and the mixture was reacted at 90°C for 6 h. After the reaction, the solvent was removed by rotary evaporation, and the mixture was purified by HPLC preparative chromatography to obtain compound 2 (0.059 g, 0.070 mmol, Y = 10.0%).

[0057] use1 It was characterized by H NMR.

[0058] 1 H NMR (500MHz, Methanol-d4) δ8.47(s,2H),8.33(s,1H),8.17(d,J=9.3Hz,1H),8.10(d,J=14.2Hz,2H), 7.96(dd,J=18.7,8.2Hz,2H),7.54(dd,J=9.2,2.5Hz,1H),7.47–7.41(m,2H),7.30(d,J=4.8Hz,4H),7. 26(d,J=7.5Hz,2H),7.12(td,J=7.9,6.6,3.4Hz,2H),6.36(d,J=14.1Hz,2H),4.29(t,J=7.8Hz,4H),2. 93(t,J=6.8Hz,4H),2.87(t,J=6.1Hz,4H),2.19(p,J=7.1Hz,4H),2.12(p,J=6.4Hz,2H),1.25(s,12H).

[0059] Example 3 Preparation of Compound 3

[0060]

[0061] S1: 2,3,3-Trimethyl-3H-indole (2 g, 12.56 mmol) and iodomethane (8.91 g, 62.80 mmol) were added to a reaction bottle containing 10 mL of acetonitrile and refluxed under nitrogen for 24 h. After the reaction, the mixture was cooled to room temperature and then washed with 50 mL of ethyl acetate to obtain the intermediate product 3-1 (1.27 g, 7.28 mmol, Y = 57.99%) as a yellow solid powder;

[0062] S2: The intermediate product 3-1 (0.50 g, 2.66 mmol) obtained in step S1, 2-chloro-3-(hydroxymethylene)-1-cyclohexene-1-carbaldehyde (0.23 g, 1.33 mmol) and sodium acetate (0.16 g, 2 mmol) were added to 10 mL of ethanol solution and refluxed at 70°C for 4 h. After the reaction, the solid was slurried in ethyl acetate and used directly in the next step (0.31 g, 0.61 mmol, Y = 45.37%).

[0063] S3: 2-Hydroxyanthraquinone (200 mg, 0.89 mmol), sodium hydride (21.40 mg, 0.89 mmol), and the intermediate product 3-2 (0.30 g, 0.58 mmol) obtained in step S2 were mixed evenly in 10 ml of N,N-dimethylformamide, and reacted at 90°C for 6 h. After the reaction, the solvent was removed by rotary evaporation and purified by HPLC preparative chromatography to obtain compound 3 (0.07 g, 0.102 mmol, Y = 17.5%).

[0064] use 1 It was characterized by H NMR.

[0065] 1 H NMR(500MHz,Methanol-d4)δ8.41(d,J=8.7Hz,1H),8.30–8.24(m,2H),7.96(d,J=16.1Hz,1H),7.91(s,1H) ,7.88(t,J=3.1Hz,2H),7.87(d,J=4.3Hz,1H),7.71(dd,J=8.6,2.7Hz,1H),7.36(t,J=6.9Hz,4H),7.25(d,J =8.1Hz,2H),7.19(t,J=7.5Hz,2H),6.22(d,J=14.2Hz,2H),4.15(q,J=7.2Hz,4H),2.99(s,1H),2.83(dd,J =14.8,8.6Hz,5H),2.14–2.08(m,2H),1.36(d,J=6.9Hz,5H),1.34(s,12H),1.28(s,3H),0.93–0.86(m,1H).

[0066] Example 4 Preparation of Compound 4

[0067]

[0068] S1: Add 5-bromo-2,3,3-trimethyl-3H-indole (0.5 g, 2.1 mmol) and iodomethane (1.12 g, 7.85 mmol) to a reaction flask containing 10 mL of acetone and reflux under nitrogen for 24 h. After completion of the reaction, cool to room temperature, wash with 50 mL of ethyl acetate, and dry with Na2SO4 to obtain intermediate 2-1 (0.37 g, 0.98 mmol, Y = 46.68%) as a reddish-brown solid powder.

[0069] S2: The intermediate product 3-1 (0.50 g, 2.66 mmol) obtained in step S1, 2-chloro-3-(hydroxymethylene)-1-cyclohexene-1-carbaldehyde (0.23 g, 1.33 mmol) and sodium acetate (0.16 g, 2 mmol) were added to 10 mL of ethanol solution and refluxed at 70°C for 4 h. After the reaction, the solid was slurried in ethyl acetate and used directly in the next step (0.25 g, 0.49 mmol, Y = 36.59%).

[0070] S3: The intermediate product 4-2 (100 mg, 0.15 mmol) obtained in step S2, 2-aminoanthraquinone (52.30 mg, 0.23 mmol), and triethylamine (0.04 g, 0.39 mmol) were mixed evenly in 10 ml of dichloromethane, and the mixture was reacted at 25°C for 24 h. After the reaction, the solvent was removed by rotary evaporation, and the mixture was purified by HPLC preparative chromatography to obtain compound 4 (0.017 g, 0.02 mmol, Y = 13.3%).

[0071] use 1 It was characterized by H NMR.

[0072] 1 H NMR(500MHz,Chloroform-d)δ8.12–8.04(m,3H),7.82(d,J=3.4Hz,1H),7.83–7.77(m,2H),7.68–7.62( m,2H),7.59(d,J=2.8Hz,1H),7.48(d,J=8.8Hz,1H),7.39(ddd,J=8.4,3.9,2.5Hz,2H),7.33(d,J=2.3H z,1H),7.03(dt,J=8.2,1.0Hz,1H),6.74(d,J=8.4Hz,1H),6.27(dt,J=8.2,0.9Hz,1H),4.61(q,J=7.0H z,2H),3.98(q,J=7.0Hz,2H),2.80–2.68(m,4H),1.72(s,5H),1.63–1.51(m,5H),1.29(t,J=6.9Hz,3H).

[0073] Performance testing

[0074] The vacuum-dried dye was accurately weighed using a 1 / 10,000 balance to prepare a 5 mmol / L DMSO dye stock solution in a brown sample bottle. The solution was stored in a refrigerator at 4°C until use. The following performance tests were performed on the compounds and intermediates prepared in Examples 1-4:

[0075] 1. The photophysical properties of the compounds prepared in Examples 1 and 2 were tested. The test results are shown in Figure 1-2 Use a pipette to measure 1.2 μL of dye stock solution and dissolve it in a quartz cuvette containing 3 mL of the solvent to be tested. Mix well to obtain a dye concentration of 2 μmol / L. Use a UV-visible spectrophotometer to measure the absorption spectrum and a fluorescence spectrophotometer to measure the absorption spectrum.

[0076] The fluorescence emission spectrum was measured by spectrophotometer under the test conditions of 25°C.

[0077] Figure 1 is the absorption spectrum of the test sample in methanol. Figure 1 It can be seen that the maximum absorption wavelengths of compounds 1 and 2 are 775 nm and 772 nm, respectively, both reaching the near-infrared region (650-900 nm).

[0078] Figure 2 is the emission spectrum of the test sample in methanol. Figure 2 It can be seen that the maximum emission wavelength of compound 1 is 792 nm, reaching the near-infrared region (650-900 nm), the red shift reaches 17 nm, and the fluorescence undergoes a certain degree of quenching, which may have good photodynamic or photothermal properties.

[0079] The absolute fluorescence quantum yields of the compounds prepared in Examples 1 and 2 were measured.

[0080] Testing method: 2 μmol / L methanol solutions of compounds 1 and 2 were prepared using dye stock solutions. The corresponding absolute fluorescence quantum yields were measured using an absolute fluorescence quantum yield meter (Hamamatsu, C11347). The absolute fluorescence quantum yields for compound 1 and compound 2 were 0.1% and 1.4%, respectively, lower than that of indocyanine green (5.9%). All tests were performed at 25°C.

[0081] The photothermal effect of the compounds of Example 1 and Example 2 was tested. A 30 μmol / L aqueous solution of compound 1 was prepared with the dye mother solution and packaged into a 0.5 ml centrifuge tube. Then, a 500 mW / cm 2 , 760nm laser irradiation, use infrared camera to record the temperature every 30s, the test lasts for 10min, the test results are shown in Figure 3 .

[0082] Depend on Figure 3 It can be seen that the photothermal conversion ability of compound 1 is significantly better than that of compound 2, and it has better photothermal properties, and can be used for photothermal therapy.

[0083] The compound prepared in Example 1 was subjected to a cytotoxicity test.

[0084] The cytotoxicity of dye molecules is assessed using the MTT assay. The principle is that succinate dehydrogenase in the mitochondria of living cells reduces exogenous MTT to water-insoluble, blue-purple crystalline formazan, which is deposited in the cells. However, dead cells do not experience this reduction. Dimethyl sulfoxide (DMSO) dissolves the formazan in the cells, and its absorbance is measured at 490 nm using a microplate reader, which indirectly reflects the number of viable cells.

[0085] 4T1 cells were seeded in a 96-well plate. After a period of incubation, a certain concentration of compound 1 was added to different wells, ranging from 0 to 30 μmol / L. After incubation for 24 hours, the cell viability was detected by MTT assay and recorded as dark cytotoxicity. The test results are shown in Figure 4 .

[0086] 4T1 cells were seeded in a 96-well plate. After a period of culture, a certain concentration of compound 1 was added to different wells, and the compound concentrations were 0 μmol / L, 1 μmol / L, 5 μmol / L, 10 μmol / L, 15 μmol / L, 20 μmol / L, 25 μmol / L and 30 μmol / L, respectively. After incubating the cells for 4 h, a 500 mW / cm 2 , 760nm laser irradiation for 10min, and then incubation for 24h. Cell activity was detected by MTT assay and recorded as cell phototoxicity. The test results are shown in Figure 4 .

[0087] Depend on Figure 4 It can be seen that even after culturing 4T1 cells with compound 1 at a maximum concentration of 30 μmol / L for 24 hours, the cells still showed a good survival rate, indicating that this type of anthraquinone and anthracene-based meso-substituted cyanine dyes have very good biocompatibility and will not cause toxic side effects on cells within the working concentration range. Therefore, they can be used in the biological and medical fields.

[0088] The compound prepared in Example 1 was subjected to a photoacoustic imaging test of mouse tumors.

[0089] The breast cancer mouse model was established by subcutaneously injecting 1×10 4 4T1 cells were used to establish a 4T1 tumor-bearing BALB / c mouse model. The tumor volume of 4T1 tumor-bearing mice was calculated as volume A = A*b 2 / 2 (A: length; b: width), the tumor volume is about 200mm 3 Afterwards, the mice were subjected to photoacoustic imaging.

[0090] Photoacoustic imaging 4T1 tumor-bearing nude mice were intratumorally injected with a 30 μmol / L saline solution of compound 1. The PA images of the mouse tumors were monitored using the InVision 128MSOT system (iThermedical, Germany). The test results are shown in Figure 5 .

[0091] Depend on Figure 5 It can be seen that the control group ( Figure 5 a) No signal, while the experimental group ( Figure 5 b) There is a photoacoustic signal, indicating that compound 1 has a significant photoacoustic effect and has the ability to perform photoacoustic imaging in vivo.

[0092] The embodiments described above are merely descriptions of preferred implementations of the present invention and are not intended to limit the scope of the present invention. Without departing from the spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should fall within the scope of protection determined by the claims of the present invention.

Claims

1. An anthraquinone and anthracene compound meso-substituted cyanine dye, characterized in that: Having the structure of general formula I: In formula I, R1 is selected from a group of the following structural formula R2 is selected from any one of an alkyl group having 1 to 5 carbon atoms, a hydroxyl group having 1 to 5 carbon atoms, a carboxyalkyl group having 1 to 5 carbon atoms, an alkylsulfonate or alkylsulfonate having 1 to 5 carbon atoms, an aryl group, an arylsulfonate or an arylsulfonate; R3 is selected from hydrogen, halogen, carboxyl, sulfonic acid or sulfonate.

2. A method for preparing the anthraquinone and anthracene compound meso-substituted cyanine dye according to claim 1, characterized in that: The following steps are involved: S1: reacting a 2,3,3-trimethylindole Y-1 containing an R3 substitution with an N-alkylating agent in a first organic solvent at a reaction temperature of 60-100° C. for 12-24 hours to obtain a compound Y-2 containing an N-R2 substituted side chain; the N-alkylating agent is selected from an alkane or a halogenated alkane containing an R2 substitution; S2: Compound Y-2 prepared in step S1, 2-chloro-3-(hydroxymethylene)-1-cyclohexene-1-carbaldehyde, sodium acetate and a second organic solvent are mixed and reacted at 60-130° C. for 1-24 hours to obtain an intermediate product Y-3; S3: The intermediate product Y-3 obtained in step S2, the compound containing R1, the first compound, and the third organic solvent are uniformly mixed and reacted at 25-80° C. for 2-8 hours to obtain anthraquinone and anthracene compound meso-substituted cyanine dye I, wherein the first compound is sodium hydride, triethylamine or potassium carbonate.

3. The method for preparing anthraquinone and anthracene compound meso-substituted cyanine dyes according to claim 2, characterized in that: In step S1, the molar ratio of the R3-substituted 2,3,3-trimethylindole Y-1 to the N-alkylating agent is 1:(1-5), and the first organic solvent is acetone, ethanol, acetonitrile, benzene, toluene or o-dichlorobenzene; in step S2, the molar ratio of compound Y-2, 2-chloro-3-(hydroxymethylene)-1-cyclohexene-1-carboxaldehyde, and sodium acetate is (2-2.4):1:(2-2.5), and the second organic solvent is benzene, toluene, o-dichlorobenzene, methanol, ethanol, propanol, butanol, acetic acid or acetic anhydride; in step S3, the molar ratio of compound Y-3, the compound containing R1, and the first compound is 1:(1-2):(1.2-4), and the third organic solvent is dichloromethane, N,N-dimethylformamide, acetonitrile, toluene or o-dichlorobenzene.

4. Use of the anthraquinone and anthracene compound meso-substituted cyanine dye according to claim 1 in the preparation of an in vivo imaging preparation or a photothermal therapy drug.

Images