A benzazepine indolinone compound, and a preparation method and application thereof

Abstract

This invention relates to the fields of organic light-emitting materials and tumor drugs, and particularly to a benzozaindolone compound, its preparation method, and its application. The structural formula of the benzozaindolone compound is shown in formula (3). This invention adopts a one-step synthesis strategy, which is simple, mild, has inexpensive and widely available substrates, and has a high conversion yield. It provides a simple and green synthetic approach for the synthesis of benzozaindolone compounds. Furthermore, the target compound (benzozaindolone compound) has excellent fluorescence luminescence properties and biocompatibility, and can be directly applied to fluorescence imaging of cancer cells and type I photodynamic therapy.

Description

Technical Field

[0001] This invention relates to the fields of organic light-emitting materials and tumor drugs, and in particular to a benzoza-indole ketone compound, its preparation method, and its application. Background Technology

[0002] Cancer is one of the major intractable diseases facing human society today. Compared with traditional cancer treatments, photodynamic therapy (PDT), by exposing the lesion site to specific light, has shown great potential in clinical applications due to its significant advantages such as non-invasiveness, high specificity, spatiotemporal controllability, and low side effects. PDT is divided into two types, Type I and Type II, based on the different sensitization mechanisms of the photosensitizer. Type II PDT is highly dependent on oxygen, and its efficacy is limited in the hypoxic tumor microenvironment. Type I PDT stimulates the triplet photosensitizer to undergo electron transfer with surrounding molecules (such as lipids, proteins, and oxygen), generating highly toxic free radicals (such as O2). - The development of high-performance type I photosensitizers (·OH) overcomes the limitations of traditional phototherapy in hypoxic tumor microenvironments. Therefore, the development of high-performance type I photosensitizers is of significant scientific importance and research value for improving the efficacy of phototherapy in complex tumor microenvironments.

[0003] Currently, type I photosensitizers have relatively simple structures, generally requiring multi-step synthesis, and many are conjugated aromatic ring structures with poor water solubility. Developing novel, biocompatible, and highly efficient luminescent type I photodynamic photosensitizers is of significant scientific importance and research value for improving the diagnosis and efficacy of phototherapy in complex tumor microenvironments. Summary of the Invention

[0004] The purpose of this invention is to provide a benzoza-indole ketone compound, its preparation method, and its application in the preparation of cell imaging or type I photodynamic therapy drugs.

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

[0006] One of the technical solutions of this invention is a benzoza-indole ketone compound with the structural formula shown in formula (3):

[0007] Equation (3);

[0008] In equation (3), R 1 R 2 R 3 R 4 Independently, it can be one of hydrogen, halogen, cyano, nitro, C1-C6 straight-chain alkyl or alkoxy, or OH;

[0009] R 5 R 6R 7 R 8 Independently, it can be hydrogen, halogen, or a C1-C6 straight-chain alkyl or alkoxy group.

[0010] The second technical solution of the present invention is a method for preparing the above-mentioned benzoza-indole ketone compounds, wherein, under acidic conditions, the compound shown in formula (1) and the compound shown in formula (2) undergo a cyclization reaction to obtain the benzoza-indole ketone compound shown in formula (3); specifically including the following steps:

[0011] The compound shown in formula (1), the compound shown in formula (2), and an acid are added to an organic solvent and reacted to obtain the benzozazaindolone compound;

[0012] Equation (1); Equation (2);

[0013] R in equation (1) 1 R 2 R 3 R 4 The same as R in claim 1 1 R 2 R 3 R 4 ;

[0014] R in equation (2) 5 R 6 R 7 R 8 The same as R in claim 1 5 R 6 R 7 R 8 ;

[0015] R in equation (2) 9 Halogens (F, Cl, Br, I);

[0016] R in equation (2) 10 It can be a halogen (F, Cl, Br, I), OH, or SH.

[0017] The third technical solution of the present invention is the application of the above-mentioned benzoza-indole ketone compounds in the preparation of drugs for cell imaging or type I photodynamic therapy.

[0018] The present invention discloses the following technical effects:

[0019] This invention employs a one-step synthesis strategy, which is simple, mild, and uses inexpensive and widely available substrates with high conversion yield. It provides a concise and green synthetic approach for the synthesis of benzoza-indole ketones. Furthermore, the target compounds (benzoza-indole ketones) exhibit excellent fluorescence and biocompatibility, and can be directly applied to fluorescence imaging of cancer cells and type I photodynamic therapy. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1 The proton NMR spectrum of the compound benzoza-indolone prepared in this invention was measured using a Bruker 400 MHz nuclear magnetic resonance spectrometer with deuterated chloroform as the solvent.

[0022] Figure 2 The carbon spectrum of the compound benzoza-indolone prepared in this invention was measured using a Bruker 400 MHz nuclear magnetic resonance spectra with deuterated chloroform as the solvent.

[0023] Figure 3 This is a schematic diagram of the crystal structure of the compound benzoza-indole ketone prepared in this invention.

[0024] Figure 4 This is a schematic diagram of the absorption and emission of the compound benzozazaindolone prepared in this invention.

[0025] Figure 5 This is a schematic diagram illustrating the reactive oxygen species generation test of the compound benzoza-indolone prepared in this invention.

[0026] Figure 6 The confocal fluorescence imaging effect of the compound benzozazide indolone prepared in this invention on HeLa cells.

[0027] Figure 7 The photodynamic therapy results of the compound benzozazonine prepared in this invention are shown.

[0028] Figure 8 The effect of generating type I reactive oxygen species (superoxide anion) of the compound benzozazaindolone prepared in this invention is shown. Detailed Implementation

[0029] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0030] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0031] 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. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this 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.

[0032] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0033] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0034] This invention addresses the challenge of complex preparation processes for existing benzoza-indole ketone compounds by providing an efficient single-step synthetic strategy. The prepared benzoza-indole ketone compounds exhibit excellent luminescent properties and good biocompatibility, allowing for direct application in HeLa cell confocal imaging. Furthermore, the materials can also serve as type I photosensitizers, demonstrating excellent photodynamic therapy effects at the cellular level. The type I photosensitizers of this invention possess novel structures, inexpensive and widely available substrates, mild reaction conditions, and simple preparation methods, demonstrating promising application prospects.

[0035] The first aspect of this invention provides a benzoza-indolone compound with the structural formula shown in formula (3):

[0036] Equation (3);

[0037] In equation (3), R 1 R 2 R 3 R 4Independently, it can be one of hydrogen, halogen, cyano, nitro, C1-C6 straight-chain alkyl or alkoxy, or OH;

[0038] R 5 R 6 R 7 R 8 Independently, it can be hydrogen, halogen, or a C1-C6 straight-chain alkyl or alkoxy group.

[0039] In this invention, the C1-C6 alkyl groups can specifically be: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, or hexyl, etc.

[0040] The alkoxy groups of C1-C6 can be: methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentoxy, or hexoxy, etc.

[0041] In a preferred embodiment of the present invention, R 1 R 2 R 3 R 4 It can be any one of the following: hydrogen, Cl, Br, cyano, nitro, -Me, -Et, -OMe, -OEt, or OH.

[0042] R 5 R 6 R 7 R 8 Independently, they are hydrogen, halogen, and -Me.

[0043] In a preferred embodiment of the present invention, the benzoza-indole ketone compound has one of the following structural formulas:

[0044] .

[0045] In a further preferred embodiment of the present invention, the benzozahexane indolone compound has one of the following structural formulas:

[0046] , , , , , , , , , , , , , , , , , , , , , , .

[0047] A second aspect of the present invention provides a method for preparing the above-mentioned benzoza-indole ketone compounds, wherein, under acidic conditions, the compound shown in formula (1) and the compound shown in formula (2) undergo a cyclization reaction to obtain the benzoza-indole ketone compound shown in formula (3); specifically including the following steps:

[0048] The compound shown in formula (1), the compound shown in formula (2), and an acid are added to an organic solvent and reacted to obtain the benzozazaindolone compound;

[0049] Equation (1); Equation (2);

[0050] R in equation (1) 1 R 2 R 3 R 4 The same as R in claim 1 1 R 2 R 3 R 4 ;

[0051] R in equation (2) 5 R 6 R 7 R 8 The same as R in claim 1 5 R 6 R 7 R 8 ;

[0052] R in equation (2) 9 Halogens (F, Cl, Br, I);

[0053] R in equation (2) 10 It can be a halogen (F, Cl, Br, I), OH, or SH.

[0054] To improve the reactivity between reacting compounds, preferably, R 1 R 2 R 3 R 4 Independently, it can be hydrogen, methyl, ethyl, propyl, methoxy, ethoxy, and propoxy with halogen; more preferably, R 1 R 2 R 3 R 4It can be any one of hydrogen, Br, methyl, or methoxy.

[0055] To improve the reactivity between reacting compounds, preferably, R 5 R 6 R 7 R 8 Individually, they can be methyl, ethyl, propyl, benzyl, or phenyl.

[0056] In some specific embodiments of the present invention, the compound represented by formula (1) can be one of formulas (1-1) to (1-6):

[0057] Equation (1-1): R 1 R 2 R 3 R 4 All are H;

[0058] Equation (1-2): Equation (1-3): ;

[0059] Equation (1-4): Equation (1-5): ;

[0060] Equation (1-6): R 1 R 2 R 3 R 4 One of them is Cl or Br, and the others are H, for example:

[0061] Equation (1-6): R 1 R 2 R 3 R 4 One of them is -NO2, and the others are H, for example:

[0062] In some specific embodiments of the present invention, the compound represented by formula (2) can be one of formulas (2-1) to (2-8):

[0063] Equation (2-1): R 5 R 6 R 7 R 8 Both are H, R 9 For F;

[0064] Equation (2-2): R 5 R 6 R 7 R 8 All are methyl, R 9 It is F.

[0065] Equation (2-3): R 5 R 6 R 7 R 8 All are ethyl, R 9 It is a halogen;

[0066] Equation (2-4): Equation (2-5): ;

[0067] Equation (2-6): Equation (2-7): Equation (2-8): .

[0068] In some specific embodiments of the present invention, the compound represented by formula (3) can be one of formulas (3-1) to (3-5):

[0069] Equation (3-1): R 1 R 2 R 3 R 4 Both are H, R 5 R 6 R 7 R 8 All are H;

[0070] Equation (3-2): R 1 R 2 R 3 R 4 As set up in equation (1-2), R 5 R 6 R 7 R 8 Set it as shown in equation (2-2);

[0071] Equation (3-3): R 1 R 2 R 3 R 4 As set up in equation (1-3), R 5 R 6 R 7 R 8 Set it up as shown in equation (2-3);

[0072] Equation (3-4): R 1 R 2R 3 R 4 As set up in equation (1-4), R 5 R 6 R 7 R 8 Set it as shown in equation (2-4);

[0073] Equation (3-5): R 1 R 2 R 3 R 4 As set up in equation (1-5), R 5 R 6 R 7 R 8 Set it as shown in equation (2-5).

[0074] In this invention, the molar amounts of the compounds shown in formula (1) and formula (2) can vary within a wide range. In order to achieve a more complete reaction and improve the utilization rate of raw materials, preferably, the molar ratio of the compound shown in formula (1) to the compound shown in formula (2) is 1:(0.5-3.0); more preferably, it is 1:(2-2.5).

[0075] In this invention, the acid can be one or more of various protic acids, such as organic acids and inorganic acids. Preferably, the acid is one or more of benzoic acid (PhCOOH), acetic acid, trifluoroacetic acid, hydrochloric acid, sulfuric acid, trifluoromethanesulfonic acid, and p-toluenesulfonic acid, and more preferably one or more of benzoic acid, hydrochloric acid, and trifluoroacetic acid. When the acid is one or more of benzoic acid, hydrochloric acid, and trifluoroacetic acid, the compound represented by formula (3) can be prepared in higher yields.

[0076] The present invention does not have a particular limitation on the amount of acid used, as long as it can provide sufficient acidic conditions for the reaction (cycloaddition reaction). Preferably, the molar ratio of the compound shown in formula (1) to the acid is 1: (1-5).

[0077] In this invention, the organic solvent can be any solvent commonly used in the field of cyclization reactions. For the specific raw materials of this invention, and considering the improvement of reaction yield, the solvent is preferably one or more of toluene, DMF, acetonitrile, dichloromethane, isopropanol, dimethyl sulfoxide, 1,4-dioxane, 1,2-dichloroethane, ethyl acetate, 1,2-dichloroethyl ether, and N-methylpyrrolidone.

[0078] The amount of organic solvent can vary within a wide range. Preferably, the ratio of the compound shown in formula (1) to the organic solvent is 1 mmol: 3-10 mL; more preferably, the ratio of the compound shown in formula (1) to the organic solvent is 1 mmol: 5-7 mL.

[0079] In a preferred embodiment of the present invention, the reaction temperature is 40-120°C, preferably 60-100°C, and the reaction time is 0.5-10 hours, preferably 2-4 hours. Stirring can also be performed during the reaction at a rate of 300-1000 rpm.

[0080] In a preferred embodiment of the present invention, the reaction is further comprising the steps of sequential extraction, washing, and purification.

[0081] According to the present invention, although the compound obtained by single-step preparation can be characterized by low-resolution mass spectrometry with a high yield, and this is also included in the scope of the present invention, in order to obtain a purer final product, it is preferable to purify the cycloaddition product to obtain a higher purity final product. For example, extraction (e.g., extraction with ethyl acetate), washing (first washing with saturated sodium carbonate solution and then washing with saturated brine), concentration and separation by silica gel column chromatography (e.g., using a 1:8 volume ratio of ethyl acetate / petroleum ether mixture as the eluent) can be performed sequentially to obtain a purer compound of formula (3).

[0082] A third aspect of the present invention provides the use of the above-mentioned benzozacinone indole ketone compounds in the preparation of medicaments for cell imaging or type I photodynamic therapy.

[0083] Unless otherwise specified, the technical solutions described in this invention are all conventional solutions in the field, and the reagents or raw materials used are all purchased from commercial channels or are publicly available unless otherwise specified.

[0084] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0085] Example 1

[0086] This embodiment illustrates the synthesis of benzo[a]azine indole ketone compounds according to the present invention:

[0087]

[0088] (1) As shown in the above reaction formula, the compound (1-1) (0.5 mmol), the compound (2-1) (1.25 mmol) and 2.5 mmol of hydrochloric acid were added to 3 mL of 1,2-dichloroethane and reacted at 100℃ oil bath temperature and 600 rpm stirring speed for 4 h. The mixture was extracted three times with ethyl acetate and washed successively with saturated sodium carbonate solution and saturated brine. The mixture was concentrated and purified by silica gel column chromatography (using a 1:8 volume ratio of ethyl acetate / petroleum ether mixture as the eluent) to obtain the compound of formula (3-1) - benzozazaindolone.

[0089] Equation (3-1): 1 H NMR (400 MHz, CDCl3) δ 7.20 (d, J = 7.2 Hz, 1H), 7.46 (t, J =7.6 Hz, 2H), 7.29 – 7.22 (m, 2H), 7.16 (d, J = 7.2 Hz, 1H), 6.91 – 6.86 (m,3H), 3.98 (t, J = 4.8 Hz, 2H), 3.23 (t, J = 5.6 Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ186.1, 152.4, 139.9, 136.1, 135.9, 133.8, 132.7, 130.0, 128.4, 127.3, 124.9,120.8, 119.3, 111.3, 108.3, 44.4, 36.2.

[0090] Example 2

[0091] This embodiment is used to illustrate the bioimaging and photodynamic therapy of benzo[a]za-indole ketone compounds of the present invention.

[0092] (1) Bioimaging experiments

[0093] HeLa cells were seeded in confocal microscopy dishes and cultured for 24 hours until they adhered. Benzodiazepine indole was then dispersed in the cell culture medium in solution. After incubation for 6 hours, the cells were first fixed with 4% paraformaldehyde to maintain cell morphology and alter cell permeability. Then, the cell nuclei were stained with commercial Hoechst 33342 dye to achieve co-localization. Finally, biological imaging was performed using a laser confocal microscope.

[0094] (2) Cytotoxicity test

[0095] The efficacy of benzozazonine indole in cytotoxicity and photodynamic therapy on HeLa cells was evaluated using the CCK-8 assay. The procedure is as follows:

[0096] HeLa cells were arranged at a density of 5 × 10⁶ 4 100 μL of benzo[a]indoline was seeded per well in 96-well plates and cultured for 24 hours until adherence. Then, different concentrations of medium containing benzo[a]indoline were prepared and added to the wells by medium exchange, and the plates were cultured for another 24 hours. Excess material was washed away with PBS, and 100 μL of CCK-8 working solution was added to each well. The plates were then incubated at 37 °C for another hour, and the absorbance at 450 nm was measured using a microplate reader.

[0097] (3) Photodynamic performance test

[0098] HeLa cells were arranged at a density of 5 × 10⁶ 4 Cells were seeded at a density of 100 μL / mL in 96-well plates and cultured for 24 hours until adherence. Subsequently, different concentrations of culture medium containing benzozacin indole were prepared and added to the well plates by medium exchange, and the plates were cultured for another 6 hours. The plates were then irradiated with a 470 nm laser for half an hour and incubated for another 3 hours. Cell viability was detected by the CCK-8 assay, using the same method as above.

[0099] To further verify the phototoxicity of benzozacinone indole, HeLa cells were seeded in 35 mm culture dishes and cultured for 24 hours; 1 × 10⁶ cells per well. 5 Cells were cultured in a medium containing 50 μM benzo[a]azine indole ketone, and the medium was added by changing the medium. After culturing for 6 hours, the cells were irradiated under a 470 nm laser for half an hour, and then incubated for 3 hours. Cells were stained with Calcein / PI cell viability and cytotoxicity assay kit according to the instructions. Cell apoptosis was observed using an inverted fluorescence microscope. The excitation wavelength of AM was 488 nm, and the excitation wavelength of PI was 559 nm.

[0100] Intracellular reactive oxygen species (ROS) generation was detected using fluorescence microscopy; a commercially available DHE fluorescent probe was used as the ROS probe; HeLa cells were seeded into 35 mm culture dishes, 1 × 10⁶ cells per well. 5 Cells were cultured for 24 hours until adherence; then, medium containing 50 μM benzo[a]azine indole was added by changing the medium; after culturing the cells for 6 hours, the cells were irradiated with a 470 nm laser for 5 min, and incubated with a DHE fluorescent probe for 30 min. After discarding the fluorescent probe, the cell nuclei were stained with commercial Hoechst 33342 dye to achieve co-localization. Finally, the fluorescence of the reactive oxygen species probe was observed by fluorescence microscopy.

[0101] Figure 1The proton NMR spectrum of the compound benzoza-indolone prepared in this invention was measured using a Bruker 400 MHz nuclear magnetic resonance spectrometer with deuterated chloroform as the solvent.

[0102] Figure 2 The carbon spectrum of the compound benzoza-indolone prepared in this invention was measured using a Bruker 400 MHz nuclear magnetic resonance spectra with deuterated chloroform as the solvent.

[0103] Figure 3 This is a schematic diagram of the crystal structure of the compound benzoza-indole ketone prepared in this invention.

[0104] Figure 4 This is a schematic diagram of the absorption and emission of the compound benzozazepine indolone prepared in this invention. Figure 4 It is known that the maximum absorption wavelength of benzozacindoline is 490 nm and the maximum fluorescence emission wavelength is 520 nm.

[0105] Figure 5 This is a schematic diagram illustrating the reactive oxygen species generation test of the compound benzozazepine indolone prepared in this invention. Figure 5 It can be seen that the fluorescence intensity of benzozacinone did not increase significantly after light irradiation when it interacted with the SOSG probe, indicating that no type II reactive oxygen species were generated.

[0106] Figure 6 The confocal fluorescence imaging effect of the compound benzozazide indolone prepared in this invention on HeLa cells is shown by... Figure 6 It is known that benzozacindoline has good luminescence and imaging effects, and plays a role in the diagnosis of cancer cells.

[0107] Figure 7The photodynamic therapy results of the compound benzozazaindolone prepared in this invention are shown in the figure (in the figure, "PBS" refers to phosphate buffer, "PBS+L" refers to phosphate buffer + laser irradiation, "50 μM" refers to a 50 μM benzozazaindolone solution, and "50 μM+L" refers to a 50 μM benzozazaindolone solution + laser irradiation. The four groups were operated under the same test conditions; the "PBS", "PBS+L", and "50 μM" groups are the control group, and "50 μM+L" is the experimental group). A commercial live / dead cell staining kit was used to determine the photodynamic therapy effect of the compound at 50 μM. Surviving cells were marked with green fluorescence, and dead cells were marked with red fluorescence. When HeLa cells were incubated with the compound for 6 hours, almost no HeLa cells died, indicating that benzozazaindolone has good biocompatibility with HeLa cells. After 6 hours of incubation, HeLa cells were treated with a 470 nm laser for 30 minutes. The results showed that a large number of cells died and the cell survival rate was very low, indicating that benzozacindoline possesses good biocompatibility and photodynamic therapeutic activity.

[0108] Figure 8 The generation effect of type I reactive oxygen species (superoxide anion) by the compound benzozazaindolone prepared in this invention is illustrated in the figure ("PBS" refers to phosphate buffered saline, and the concentration of benzozazaindolone solution is 50 μM. Both groups were operated under the same test conditions). The type of reactive oxygen species generated by benzozazaindolone in cells was detected using a commercially available DHE fluorescent probe. HeLa cells were seeded into 35 mm culture dishes, 1 × 10⁶ cells per well. 5 Cells were cultured for 24 hours until adherence; then, PBS and medium containing 50 μM benzozazaindolone were added via medium exchange. After 6 hours of cell culture, cells were irradiated with a 470 nm laser for 5 min, incubated with a DHE fluorescent probe for 30 min, and the fluorescent probe was discarded. The cell nuclei were then stained with commercial Hoechst 33342 dye to achieve co-localization. Finally, the fluorescence of the reactive oxygen species probe was observed using a fluorescence microscope. Results showed that DHE, after binding with superoxide anions in the cells and being oxidized, entered the cell nucleus and bound to DNA, emitting red fluorescence. Compared with the non-illuminated group, the illuminated group showed significant red fluorescence in the cell nuclei, clearly demonstrating that benzozazaindolone generates superoxide anions under laser irradiation, exhibiting photodynamic therapeutic effects.

[0109] The present invention also prepared the following benzoza-indolone compounds using a preparation method similar to that in Example 1. , , , , , , , , , , , , , , , , , , , , , The above-mentioned benzoza-indole ketone compounds were subjected to the same performance verification as in Example 1. The results showed that the above-mentioned benzoza-indole ketone compounds could achieve the same effect as in Example 1. Similar technical effects.

[0110] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. The application of a benzozacinone indole ketone compound in the preparation of a drug for type I photodynamic therapy, characterized in that, The structural formula of the benzo[a]azine indole ketone compound is shown in formula (3): Equation (3); In equation (3), R 1 R 2 R 3 R 4 Independently, it can be one of hydrogen, halogen, cyano, nitro, C1-C6 straight-chain alkyl or C1-C6 alkoxy, or OH; R 5 R 6 R 7 R 8 Independently, it can be hydrogen, halogen, C1-C6 straight-chain alkyl, or C1-C6 alkoxy.

2. The application according to claim 1, characterized in that, R 1 R 2 R 3 R 4 It can be any one of the following: hydrogen, Cl, Br, cyano, nitro, -Me, -Et, -OMe, -OEt, or OH. R 5 R 6 R 7 R 8 Independently, they are hydrogen, halogen, and -Me.

Images