A naphthaleneimide-TB compound and its synthesis method and application

Abstract

The present invention provides a naphthalimide-TB compound and its synthesis method and application. The structural formula is shown below: #imgabs0# The naphthalimide-TB compound 8 has a simple synthesis method and convenient post-processing; has a large Stokes shift, large fluorescence brightness, excellent solid-state luminescence, and exhibits excellent luminescence performance; has a wide pH range and can be used in human physiological environments; has an effective and good response to viscosity and has the potential to become a viscosity-responsive fluorescent probe; has a significant aggregation-induced emission (AIE) effect; has a strong affinity for Fe 3+ With the ability to identify, it is expected to become an excellent Fe 3+ Fluorescent probe; has high inhibition rates on A549 and HepG‑2 cells under both dark and light conditions, and has the potential to be developed into a new anti-tumor drug.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis and analytical chemistry, and specifically relates to a naphthalene imide having excellent optical properties. Synthesis of (TB) compounds and their applications in viscosity response, metal ion recognition and anti-tumor. Background Art

[0002] Fe 3+ It is one of the main transition metals and plays an important role in oxygen transport and transcriptional regulation in the human body. 3+ Slight changes in Fe can lead to cellular metabolic dysfunction and cause diseases such as liver and kidney damage, anemia, cirrhosis and heart failure. In addition, industrial activities frequently process Fe 3+ It may pose a significant threat to nearby water sources. Therefore, monitoring Fe 3+ Fe levels are crucial for human health and water quality safety in the environment. Various detection and evaluation techniques have been widely used to detect Fe 3+ , including mass spectrometry, chromatography, voltammetry, synchrotron radiation X-ray spectroscopy (SRXRS), and chemiluminescence. Some of these techniques require expensive experimental setups and use complex toxic solvents during post-processing. Compared with these traditional techniques, fluorescence-based detection methods have the advantages of low cost, high sensitivity, and good selectivity. They can detect trace levels of various pollutants and biological samples in a shorter time.

[0003] 1,8-Naphthalimide is a fluorophore with excellent luminescent properties. It has the advantages of easy modification, good photostability, and high fluorescence brightness. It is widely used in fields such as ion detection, molecular recognition, and bioimaging. Its luminescent properties are closely related to its molecular structure. Traditional naphthalimide fluorescent dyes have a highly planar structure with strong intermolecular π-π stacking, which leads to large self-absorption and susceptibility to aggregation-induced fluorescence quenching (ACQ). Their Stokes shift is small, making them susceptible to the influence of excitation light and scattered light. Naphthalimides with highly rigid and sterically hindered substituents on the aromatic ring have a propeller-shaped molecular conformation and often exhibit aggregation-induced emission (AIE) luminescence properties. Therefore, modifying naphthalimide to obtain AIE fluorescent compounds with large Stokes shifts is beneficial to expanding its application range.

[0004] Base (TB for short) and its derivatives have a unique V-shaped skeleton and a long conjugated structure. They have multiple transition modes (π-π*, n-π*, spatial transition) under photon excitation. Theoretically, they have a large molar absorption coefficient and are an excellent basic skeleton for ultraviolet light absorption materials.

[0005] Therefore, the present invention designs and synthesizes a class of naphthalimide-TB compounds by introducing naphthalimide groups into the TB skeleton, and applies them to the fields of viscosity response, metal ion recognition and tumor photodynamic therapy. Summary of the Invention

[0006] Technical problem: The purpose of the present invention is to provide a class of naphthaleneimide-TB compounds, their synthesis methods and applications. By introducing naphthaleneimide groups into the TB skeleton, a class of naphthaleneimide-TB compounds is designed and synthesized, and applied to the fields of viscosity response, metal ion recognition and photodynamic therapy.

[0007] Technical solution: A naphthaleneimide-TB compound of the present invention has a structural formula as shown in the following naphthaleneimide-TB compound 8:

[0008]

[0009] The method for synthesizing a naphthalimide-TB compound according to the present invention comprises the following steps:

[0010] Step 1, 3-methoxy-4-bromoaniline 1 reacts with paraformaldehyde 2 to obtain the first intermediate 3, and the reaction formula is as follows:

[0011]

[0012] Step 2: The first intermediate 3 reacts with trimethyl borate to obtain the second intermediate 4. The reaction formula is as follows:

[0013]

[0014] Step 3, 4-bromonaphthalic anhydride 5 and N 1 ,N 1 -Dimethyl-1,3-diaminopropane 6 is reacted to obtain the third intermediate 7, and the reaction formula is as follows:

[0015]

[0016] Step 4: The second intermediate 4 reacts with the third intermediate 7 to obtain the product naphthalene imide-TB compound 8. The reaction formula is as follows:

[0017]

[0018] Application of the naphthaleneimide-TB compound of the present invention in the preparation of a viscosity probe.

[0019] The naphthaleneimide-TB compound of the present invention is used as Fe 3+ Application of fluorescent probes in metal ion recognition.

[0020] The invention relates to the use of the naphthalimide-TB compound in the preparation of cancer photodynamic therapy drugs.

[0021] The application of the invention in preparing cancer photodynamic therapy drugs is aimed at inhibiting human liver cancer HpeG2 cells and human lung cancer A549 cells.

[0022] Beneficial effects:

[0023] 1. The synthesis method is simple and the post-processing is convenient;

[0024] 2. The product has excellent luminescence properties: large Stokes shift, high fluorescence brightness, significant AIE properties and excellent solid-state luminescence.

[0025] 3. The product has a wide pH range and can be used in human physiological environments.

[0026] 4. The product responds effectively to viscosity and has the potential to become a viscosity-responsive fluorescent probe.

[0027] 5. Product to Fe 3+ With the ability to identify, it is expected to become an excellent Fe 3+ Fluorescent probes;

[0028] 6. The product has high dark toxicity and photodynamic therapy effect on A549 and HepG-2 cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 : (a) UV absorption and (b) fluorescence emission spectra of naphthaleneimide-TB compound 8 in different solvents.

[0030] Figure 2 : (a) UV absorption and (b) fluorescence emission spectra of the second intermediate 4 and naphthaleneimide-TB compound 8 in solution.

[0031] Figure 3 : Solid-state fluorescence emission spectra of the second intermediate 4 and the naphthalimide-TB compound 8.

[0032] Figure 4 :(a) Fluorescence emission spectra of naphthaleneimide-TB compound 8 at different viscosities and (b) line graph.

[0033] Figure 5 :(a) Changes in fluorescence intensity of naphthaleneimide-TB compound 8 at different temperatures; (b) Fluorescence emission spectra of 8 before and after protein denaturation.

[0034] Figure 6 : (a) Fluorescence emission spectra of naphthalimide-TB compound 8 at different pH values ​​and (b) line graph.

[0035] Figure 7 :(a) Fluorescence emission spectra of naphthaleneimide-TB compound 8 in different ratios of THF / H2O and (b) line graph (the embedded figure is a photo of 10% and 90% water content under UV light).

[0036] Figure 8 : Scanning electron micrograph of the product naphthalimide-TB compound 8 at a water content of 90%.

[0037] Figure 9 : (a) Fluorescence emission spectra of naphthalimide-TB compound 8 in the presence of different metal ions and (b) bar graph.

[0038] Figure 10 :(a) Naphthalimide-TB compound 8 at different concentrations of Fe 3+ (b) Fluorescence emission spectra in the presence of β-lactamase and (c) standard curve.

[0039] Figure 11 :Naphthalimide-TB compound 8-Fe 3+ The Job's curve of the system.

[0040] Figure 12 : (a) Survival rate of A549 cells or (b) HepG-2 cells incubated with different concentrations of naphthalimide-TB compound 8 after 30 minutes of illumination or in the dark. DETAILED DESCRIPTION

[0041] The present invention will be further described below with reference to the embodiments.

[0042] The embodiments of the present invention are described in detail below. The embodiments described below are exemplary and are only used to explain the present invention, and are not to be construed as limiting the present invention. It will be understood by those skilled in the art that various changes and modifications may be made to the present invention without departing from the spirit and scope of the present invention.

[0043] The present invention designs and synthesizes a class of naphthalimide-TB compounds by introducing naphthalimide groups into the TB skeleton, and applies them to the fields of viscosity response, metal ion recognition and photodynamic therapy.

[0044] The structural formula of the naphthaleneimide-TB compound is shown in Table 1:

[0045] Table 1 Synthesis of naphthaleneimide-TB compound 8

[0046]

[0047] In this embodiment, 4-bromo-3-methoxyaniline, paraformaldehyde, n-butyl lithium, trimethyl borate, 4-bromo-1,8-naphthalene dicarboxylic anhydride, N,N-dimethyl-1,3-diaminopropane, etc. are used as raw materials to prepare the product through a multi-step reaction. The steps include:

[0048] 3-Methoxy-4-bromoaniline 1 reacts with paraformaldehyde to obtain a first intermediate 3, the first intermediate 3 reacts with trimethyl borate to obtain a second intermediate 4, 4-bromonaphthalic anhydride 5 reacts with N,N-dimethyl-1,3-diaminopropane to obtain a third intermediate 7, and the second intermediate 4 reacts with the third intermediate 7 to obtain the product naphthaleneimide-TB compound 8.

[0049] The compounds of the following examples were prepared by the above synthesis method:

[0050] (1) 3-Methoxy-4-bromoaniline 1 (60 mmol) and paraformaldehyde 2 (150 mmol) were added to a 250 mL round-bottom flask. The flask was placed in a low-temperature tank and the temperature was adjusted to -15°C. 120 mL of trifluoroacetic acid was slowly added dropwise through a constant pressure dropping funnel. After about 30 minutes of complete addition, the reaction system was moved to a 25°C environment and reacted for 7 days. After the reaction was complete (TLC tracking), it was quenched with ice water, the pH was adjusted to 7 with ammonia water, and the mixture was cooled to room temperature. The mixture was filtered, washed three times with purified water, and recrystallized from acetone to obtain the first intermediate 3 (65%).

[0051]

[0052] Synthesis of the first intermediate 3 of Formula 1

[0053] (2) The first intermediate 3 (5.0 mmol) was weighed and placed in a 100 mL double-necked round-bottom flask, which was placed in a low-temperature tank and adjusted to -45°C. Under argon protection, 20 mL of anhydrous tetrahydrofuran was added. After ten minutes, 5.0 mL of n-butyl lithium (1.6 mol·L -1 ), stirred for 1 hour, then slowly added 2.0 mL of trimethyl borate, and continued to react at room temperature for 6 hours. After the reaction was complete (TLC tracking), water was added to quench the reaction, and dichloromethane was extracted. The crude product was purified by column chromatography (V 石油醚 :V 乙酸乙酯 =10:1) to give the second intermediate 4 (70%).

[0054]

[0055] Synthesis of the second intermediate 4 of Formula 2

[0056] (3) 4-Bromonaphthalene dicarboxylic anhydride 5 (3.6 mmol) was placed in a 100 mL round-bottom flask, 40 mL of anhydrous ethanol was added, and the temperature was raised to 80 °C while stirring. After boiling, N1 ,N 1 1,3-Dimethyl-1,3-diaminopropane 6 (0.5 mL) was condensed and refluxed for 2 h. TLC was performed. After the reaction was complete, the mixture was cooled to room temperature and 40 mL of deionized water was added to form a light yellow viscous suspension. The suspension was filtered and the filter cake was washed three times with deionized water. The mixture was then dried under vacuum at 60°C for 6 h to obtain the third intermediate 7 (95%).

[0057]

[0058] Synthesis of intermediate 7 of formula 3

[0059] (4) The second intermediate 4 (1.0 mmol), the third intermediate 7 (2.2 mmol), tetrakis(triphenylphosphine)palladium (6.0 mmol) and potassium carbonate (0.1 mmol) were added to a 50 mL round-bottom flask in sequence. After three evacuations, 7 mL of anhydrous toluene, 2 mL of ethanol and 1 mL of purified water were added and the mixture was reacted at 90°C overnight. After the reaction was complete (TLC tracking), water was added to quench the reaction, and the mixture was extracted with ethyl acetate. The crude product was purified by column chromatography (V 二氯甲烷 :V 甲醇 =10:1), and recrystallized from petroleum ether and ethyl acetate to obtain the product naphthalene imide-TB compound 8 (54%).

[0060]

[0061] Synthesis of naphthaleneimide-TB compound 8 of formula 4

[0062] 6,6'-(3,9-dimethoxy-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine-2,8-diyl)bis(2-(3-(dimethylamino)propyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione)(18)

[0063] (s,3H),2.45(t,J=7.2Hz,4H),2.26(s,12H),1.91(p,J=7.2Hz,4H). 13 C NMR (100MHz, CDCl3) δ164.27,156.28,149.79,143.77,133.24,131.17,130.79,129.82,128.39,1 26.56,124.23,122.76,121.76,119.94,107.61,58.07,57.16,55.66,45.20,38.72,29.78,25.93.

[0064] Solvation effect

[0065] The solvation effect of the compounds of the present invention was tested, and the specific test protocol is as follows:

[0066] The naphthaleneimide-TB compound 8 was prepared with n-hexane (n-Hexane), toluene (Toluene), tetrahydrofuran (THF), chloroform (CHCl3), ethyl acetate (EA), acetonitrile (MeCN), methanol (MeOH) and dimethyl sulfoxide (DMSO) to a concentration of 1×10 -5 mol·L -1 The UV absorption and fluorescence emission spectra of the solution were tested. Figure 1 ).

[0067] Depend on Figure 1 It can be seen that the UV absorption peaks of naphthaleneimide-TB compound 8 in different solvents are not much different, indicating that the solvent has little effect on its UV absorption. The UV absorption of naphthaleneimide-TB compound 8 appears at around 340nm, which is attributed to the π-π * The B band absorption caused by the transition. Naphthalimide-TB compound 8 has no fluorescence emission peak in the low polarity n-hexane and the high polarity acetonitrile, methanol and DMSO. The main reason is that the solubility of naphthalimide-TB compound 8 in these solvents is low.

[0068] Photophysical properties

[0069] The photophysical properties of the second intermediate 4 and the naphthaleneimide-TB compound 8 in solution were investigated. The specific experimental scheme is as follows:

[0070] Weigh 10 -5 mol of the second intermediate 4 and the naphthaleneimide-TB compound 8 were diluted with the solution to a concentration of 1×10 - 5 mol / L, and tested its UV absorption, fluorescence emission and solid-state fluorescence emission spectrum (1×10 -5 mol·L -1 , Figure 2 ).

[0071] The spectral data of the second intermediate 4 and the naphthaleneimide-TB compound 8 are shown in Table 2.

[0072] Table 2 Spectral data of the second intermediate 4 and the naphthaleneimide-TB compound 8

[0073]

[0074] a UV absorption wavelength in solution; bMolar extinction coefficient ε = A / bC, unit is 1×10 5 L·mol -1 cm -1 ; c Fluorescence emission wavelength in solution; d Stokes shift in solution; e Relative fluorescence quantum yield (reference: quinine sulfate); f Fluorescence brightness FB = ε*Φ, unit is L·mol -1 cm -1 ;g solid-state excitation wavelength; h solid-state fluorescence emission wavelength; i Solid-state Stokes shift.

[0075] Combine Figure 2 As shown in Table 2, compared with the second intermediate 4, the λ abs There is an obvious red shift, and the molar absorption coefficient of the naphthaleneimide-TB compound 8 is 2.3 times that of the second intermediate 4. This is because the structure of the naphthaleneimide-TB compound 8 is conducive to electron flow, thereby increasing the molar absorption coefficient.

[0076] Naphthalimide-TB compound 8 has a larger λ em (534 nm), with its emission tail entering the red range. The relative fluorescence quantum yield and brightness of naphthalimide-TB compound 8 were significantly increased, and the Stokes shift in both solution and solid state was significantly improved. The large Stokes shift and red emission minimize the effects of excitation and scattered light on fluorescence emission, effectively shielding against biological background interference, and facilitating its expanded applications in ion detection, PDT, and other areas.

[0077] Viscosity response

[0078] Methanol was used as solvent to prepare the naphthaleneimide-TB compound 8 to a concentration of 1×10 -4 mol·L -1 Take five 10 mL volumetric flasks, pipette 1.0 mL of the working solution into each volumetric flask, add 0.0 mL, 2.0 mL, 4.0 mL, 6.0 mL, and 8.0 mL of glycerol, respectively, and dilute to volume with methanol to make the concentration of naphthaleneimide-TB compound 8 1×10 -5 mol·L -1 , and its fluorescence emission spectrum (λ ex =340nm, slit: 5 / 10nm, Figure 4 ).

[0079] Depend on Figure 4It can be seen that with the increase of propylene glycol content, the fluorescence intensity of naphthaleneimide-TB compound 8 gradually increases. This may be because the increase in viscosity restricts the intramolecular rotation of naphthaleneimide-TB compound 8, increases its molecular rigidity, and increases the fluorescence intensity.

[0080] The above results indicate that naphthaleneimide-TB compound 8 has the potential to be a viscosity-responsive fluorescent probe. Therefore, a protein aggregation experiment was conducted using egg white as a sample: First, the stability of 8 was studied. Naphthaleneimide-TB compound 8 was prepared with DMSO as a solvent to a concentration of 1×10 -4 mol·L -1 Take five 10 mL volumetric flasks, pipette 1.0 mL of the working solution of 8 and 1.0 mL of PBS buffer solution into each volumetric flask, and adjust the volume with DMSO to make the concentration of 1 × 10 -5 mol·L -1 Each volumetric flask was placed in a water bath at 20℃, 40℃, 60℃, 80℃ and 100℃ for five minutes, and the changes in fluorescence intensity (λ ex =260nm, slit: 2.5 / 5nm, Figure 5 a).

[0081] Then, naphthalimide-TB compound 8 was prepared with DMSO as solvent to a concentration of 1×10 -4 mol·L -1 The working solution was prepared with PBS to a concentration of 1 × 10 -4 mol·L -1 Take two 10 mL volumetric flasks, pipette 1.0 mL of the working solution of naphthalimide-TB compound 8 and 1.0 mL of the egg white solution into each volumetric flask, and adjust the volume with DMSO so that the concentrations of naphthalimide-TB compound 8 and egg white in the system are both 1×10 -5 mol·L -1 Each volumetric flask was placed in a water bath at 25°C and 95°C for five minutes, and its fluorescence emission spectra (λ ex =260nm, slit: 2.5 / 5nm, Figure 5 b).

[0082] Depend on Figure 5 As can be seen, the fluorescence intensity of naphthalimide-TB compound 8 changes little with increasing temperature, indicating its good thermal stability. The fluorescence intensity of naphthalimide-TB compound 8 increases significantly after protein denaturation compared to before denaturation. This demonstrates that naphthalimide-TB compound 8 can be used as a "light-up" probe to detect protein changes.

[0083] pH response

[0084] DMSO was used as solvent to prepare the naphthalimide-TB compound 8 at a concentration of 1×10 -4 mol·L -1 1.0 mL of the working solution was measured and placed in a 10 mL volumetric flask, followed by the addition of 1.0 mL of a buffer solution with a pH value of 2-10 (citric acid / disodium hydrogen phosphate system was selected when the pH value was 2-8, and sodium bicarbonate / sodium carbonate system was selected when the pH value was 9-10), and DMSO was used to adjust the volume to make the concentration of the naphthalimide-TB compound 8 1×10 -5 mol L -1 , the fluorescence emission spectrum (λ ex =340nm, slit: 10 / 10nm, Figure 6 ).

[0085] Depend on Figure 6 It can be seen that the fluorescence intensity of naphthalimide-TB compound 8 does not change significantly when the solution pH is 2-10, indicating that it can be used under various pH conditions.

[0086] AIE effect

[0087] The naphthalimide-TB compound 8 was prepared with THF as solvent to a concentration of 1×10 -4 mol·L -1 Take 9 10mL volumetric flasks, transfer 1.0mL of the working solution to each volumetric flask, add 1.0-9.0mL of distilled water and THF to the volume, so that the concentration of naphthalene imide-TB compound 8 is 1×10 -5 mol L -1 , the fluorescence emission spectrum (λ ex =340nm, slit: 2.5 / 5nm, Figure 7 ).

[0088] like Figure 7 As shown, the fluorescence intensity of naphthalimide-TB compound 8 gradually increases with increasing water content, indicating that naphthalimide-TB compound 8 is an AIE-active molecule. That is, the luminescence of naphthalimide-TB compound 8 is almost invisible in solution, but highly luminescent in the aggregated state. The enhanced emission of naphthalimide-TB compound 8 may be attributed to the distorted geometry, which spatially interferes with the close packing by increasing the intermolecular distance. The intermolecular quenching interaction is suppressed to some extent by the increased intermolecular distance caused by the distorted geometry of naphthalimide-TB compound 8. Studies have shown that the long molecular distance may reduce the distance-dependent intermolecular quenching effect, thereby generating strong fluorescence in the aggregated state.

[0089] like Figure 7As shown, the fluorescence intensity of naphthalimide-TB compound 8 gradually increases with increasing water content, indicating that naphthalimide-TB compound 8 is an AIE-active molecule. That is, the luminescence of naphthalimide-TB compound 8 is almost invisible in solution, but highly luminescent in the aggregated state. The enhanced emission of naphthalimide-TB compound 8 may be attributed to the distorted geometry, which spatially interferes with the close packing by increasing the intermolecular distance. The intermolecular quenching interaction is suppressed to some extent by the increased intermolecular distance caused by the distorted geometry of naphthalimide-TB compound 8. Studies have shown that the long molecular distance may reduce the distance-dependent intermolecular quenching effect, thereby generating strong fluorescence in the aggregated state.

[0090] Recognition of metal ions

[0091] The naphthaleneimide-TB compound 8 was tested with Na + , K + Mg 2+ , Ca 2+ 、Fe 2+ 、Cu 2+ 、Zn 2+ 、Al 3+ 、Fe 3+ The fluorescence emission spectrum (λ ex =340nm, slit: 5 / 10nm, Figure 9 ).

[0092] The changes in fluorescence intensity of naphthaleneimide-TB compound 8 after adding metal ions are shown in Table 3.

[0093] Table 3 Effects of naphthaleneimide-TB compound 8 on different metal ions

[0094]

[0095] a The change rate of the fluorescence intensity of the compound after adding metal ions is η = (I-I0) / I0×100%. "-" means no

[0096] Combine Figure 9 As can be seen from Table 3, the addition of Fe 3+ and Cu 2+ After addition of Fe ions, the fluorescence intensity of naphthaleneimide-TB compound 8 decreased by 99% and 55%, respectively. However, when other metal ions were added, the change in fluorescence intensity was negligible, indicating that naphthaleneimide-TB compound 8 has a strong effect on Fe 3+ It has the best recognition effect; the interference ions have little effect on naphthalene imide-TB compound 8, indicating that naphthalene imide-TB compound 8 has the best recognition effect on Fe 3+ and Cu 2+ With more efficient recognition. Naphthalimide-TB compound 8 and Fe3+ After the action, λ em There is an obvious red shift, indicating that it is related to Fe 3+ Some kind of reaction may have occurred.

[0097] The naphthaleneimide-TB compound 8-Fe 3+ The standard curve of the system (λ ex =340nm, slit: 10 / 10nm, Figure 10 ).

[0098] Depend on Figure 10 It can be seen that when Fe 3+ The concentration was 2×10 -5 -9×10 -5 mol·L -1 Range, as Fe 3+ As the concentration increases, the fluorescence intensity of naphthalimide-TB compound 8 at 499 nm gradually increases, and the fluorescence intensity is similar to that of Fe 3+ The concentration has an obvious linear relationship, R 2 is 0.99595, and the linear equation y = -236.80714 × 10 5 x+2387.31429. The Naphthalimide-TB Compound 8 was calculated to have a strong affinity for Fe. 3+ The LOD is 5.6×10 -7 mol·L -1 , which is expected to selectively detect Fe in water environments 3+ content.

[0099] To further explore the recognition of Fe by naphthaleneimide-TB compound 8 3+ The Job's curve (λ ex =340nm, slit: 10 / 10nm, concentration: 1×10 -5 mol·L -1 , Figure 11 .

[0100] Depend on Figure 11 It can be seen that the naphthaleneimide-TB compound 8 and Fe 3+ No stable complex was formed. The naphthaleneimide-TB compound 8 had no effect on Fe 3+ The recognition of is the result of other types of intermolecular forces.

[0101] Extracorporeal photodynamic therapy

[0102] The dark toxicity and phototoxicity of 8 samples to human non-small lung cancer cells (A549) and human liver cancer cells (HepG-2) were tested by standard MTT assay. Figure 12 ).

[0103] like Figure 12As shown, when the concentration of naphthalimide-TB compound 8 was as low as 6.25 μmol·L -1 When the concentration of naphthaleneimide-TB compound 8 was 6.25 μmol·L, the survival rate of A549 cells was only 50%. When the concentration was further increased, the killing rate of A549 cells reached 90% regardless of whether the cells were exposed to light. -1 When the concentration of naphthaleneimide-TB compound 8 was high, the survival rate of HepG-2 cells under light conditions was only 10%. At higher concentrations, the dark toxicity of naphthaleneimide-TB compound 8 was also greater. These results indicate that at higher concentrations, both the dark toxicity and phototoxicity of naphthaleneimide-TB compound 8 were higher, while at lower concentrations, naphthaleneimide-TB compound 8 exhibited excellent photodynamic therapy effects.

[0104] Table 4. The half inhibition rate (IC) of naphthalimide-TB compound 8 on two cell lines 50 )

[0105]

[0106] As shown in Table 4, regardless of whether light is applied or not, naphthaleneimide-TB compound 8 has extremely low IC 50 values ​​(6.2 and 5.0 μmol·L -1 and 3.4 and 6.7 μmol·L -1 ), indicating that 8 has excellent inhibitory effect on A549 and HepG-2 cells and has the possibility of being applied in real treatment.

[0107] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A naphthalimide-TB compound, characterized in that: Its structural formula is shown below as naphthaleneimide-TB compound (8):

2. A method for synthesizing a naphthalimide-TB compound according to claim 1, characterized in that: The following steps are involved: Step 1, 3-methoxy-4-bromoaniline (1) reacts with paraformaldehyde (2) to obtain a first intermediate (3), and the reaction formula is as follows: Step 2: The first intermediate (3) reacts with trimethyl borate to obtain the second intermediate (4). The reaction formula is as follows: Step 3, 4-bromonaphthalic anhydride (5) and N 1 ,N 1 -dimethyl-1,3-diaminopropane (6) is reacted to obtain the third intermediate (7), and the reaction formula is as follows: Step 4: The second intermediate (4) reacts with the third intermediate (7) to obtain the product naphthalene imide-TB compound (8). The reaction formula is as follows:

3. Use of the naphthalimide-TB compound according to claim 1 in the preparation of photodynamic therapy drugs for human liver cancer HpeG2 cells and human lung cancer A549 cells.

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