1, 8-disubstituted tryptanthrin derivative as well as preparation method and application thereof

Abstract

The invention discloses a 1, 8-disubstituted tryptanthrin derivative and application of the 1, 8-disubstituted tryptanthrin derivative to prevention and treatment of phytopathogen and anti-tumor activity, the general formula of the derivative is shown in (I), and the test result of the compound shown in the general formula on the bacterial activity of phytopathogen shows that the compound has a good antibacterial effect on Xanthomonas oryzae pv. Oryzae, Xanthomonas citri pv. Citri and the like, and can be used for preventing and treating the phytopathogen. The method can be used for developing novel agricultural bactericides. Meanwhile, results of the compound shown in the general formula on tumor cells show that the compound has good in-vitro anti-tumor activity on human chronic myelogenous leukemia cells K562, human lung cancer cell lines A549, human liver cancer cells HepG2, human prostate cancer cells PC3 and the like, and can be used for researching novel anti-tumor drugs. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the field of chemical technology, and in particular to a method for preparing a class of 1,8-disubstituted tryptanthrin derivatives and their application in antibacterial activity and anti-tumor research. Background Art

[0002] Plant-derived natural products mainly refer to air-dried processed products of plants, crude extracts of plants, and isolated effective active ingredients. They have the advantages of wide sources, diverse structures, biodegradability, multiple drug resistance, and ecological compatibility. Therefore, developing them into green, low-toxic, and highly effective agents is considered an important strategy for healthy ecology and sustainable development. Natural alkaloid compounds are an important source for drug development and an important way to discover lead structural compounds. They are rich in sources and play a key role in drug discovery. Compared with traditional drugs, they have a wide range of biological activities, multi-target pharmacodynamic effects, unique modes of action, and good biological and environmental compatibility. Using natural active small molecule compounds as the lead discovery and rational design and optimization through structural diversity is the current hot spot and direction of new drug research.

[0003] Tryptanthrin is an indolequinazoline alkaloid, first extracted from the traditional Chinese medicine Radix Isatidis and Folium Isatidis, and as the main active ingredient, it has a good antibacterial and anti-inflammatory effect. A large number of studies have shown that tryptanthrin derivatives have significant pharmacological properties and biological activities, including antibacterial activity, anti-inflammatory activity, antiviral activity, antiparasitic activity, anti-tuberculosis activity, anti-tumor activity and other activities, which have attracted widespread attention. Because tryptanthrin, like most natural alkaloids, has low solubility, mild microbial toxicity and moderate biological activity, it is necessary to modify and optimize its structure through chemical means to make it an ideal candidate drug.

[0004] Aliphatic amine compounds are of great significance in drug design and agrochemical development. Studies have found that nearly 75% of unique organic small molecule drugs contain nitrogen atoms, which is an important branch in the application of organic chemistry. Electron-rich nitrogen atoms are not only easy to accept or donate protons, but also easy to establish various weak bond interactions, such as the bond formation of hydrogen-nitrogen compounds, dipole-dipole interactions, hydrophobic effects, van der Waals forces and π-π stacking effects, which increase their importance in the field of medicinal chemistry and enhance the hydrophilicity of compounds, so that they can bind to various enzymes and receptors in biological targets with high affinity to improve the biological activity of compounds.

[0005] In 2001, Kataoka et al. [Kataoka, M.; Hirata, K.; Kunikata, T.; Ushio, S.; Iwaki, K.; Ohashi, K.; Ikeda, M.; Kurimoto, M. Antibacterial action of tryptanthrin and kaempferol, isolated from the indigo plant (Polygonum tinctorium Lour), against Helicobacter pylori-infected Mongolian gerbils [J]. J. Gastroenterol., 2001, 36, 5-9] evaluated the in vitro inhibitory effect of tryptanthrin, a compound isolated from the indigo plant, on Helicobacter pylori against gerbils. They found that tryptanthrin could reduce the number of Helicobacter pylori colonies in a dose-dependent manner. Oral administration could significantly reduce the number of colonies in the stomach of gerbils. Combination treatment with antibiotics could reduce the dose of antibiotics, thereby alleviating the impact of toxic side effects.

[0006] In 2010, Bandekar et al. [Bandekar, PP; Roopnarine, KA; Parekh, VJ; Mitchell, TR; Novak, MJ; Sinden, RR Antimicrobial activity of tryptanthrins in Escherichia coli [J]. J. Med. Chem., 2010, 53, 3558-3565.] studied the effects of tryptanthrin and its derivatives on the growth, survival and mutagenesis of Escherichia coli. At a concentration as low as 5 μM, the analogues of the nitrogen atom at the 4th position of tryptanthrin could prevent the growth of Escherichia coli culture, and had higher antibacterial efficacy than other substituted tryptanthrin 4-aza derivatives. Compounds containing 6-oxime groups are also very effective fungicides, but tryptanthrin compounds containing both 6-oxime and 4-nitrogen heteroatoms have poor antibacterial activity, which may be due to the oxime group affecting the antibacterial effect of the nitrogen heteroatom.

[0007] In 2011, Kawakami et al. [Kawakami, J.; Matsushima, N.; Ogawa, Y.; Kakinami, H.; Nakane, A.; Kitahara, H.; Nagaki, M.; Ito, S. Antibacterial and antifungal activities of tryptanthrin derivatives [J]. T. Mater. Res. Soc. Jpn., 2011, 36, 603-606.] evaluated the antibacterial activity of 13 synthetic tryptanthrin derivatives against Gram-positive bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and Malassezia furfur. The substituent group significantly affected the antibacterial activity of tryptanthrin, among which the halogen-substituted derivatives had the strongest inhibitory effect.

[0008] In 2017, Costa et al. [Costa, DCM; Azevedo, MMB; Silva, DOE; Romanos, MTV; Souto-Padrón, TCBS; Alviano, CS; Alviano, DS In vitro anti-MRSA activity of Couroupita guianensis extract and its component Tryptanthrin [J]. Nat. Prod. Res., 2017, 31, 2077-2080.] tested the activity of Couroupita guianensis extract from Brazil against bacteria, filamentous fungi and yeasts and found that the dichloromethane extract had the strongest inhibitory effect on MRSA (MIC was 156 μg / mL). Its main active ingredient, tryptanthrin, has an antibacterial activity MIC of 62.5 μg / mL against MRSA.

[0009] In 2019, Gaitanis et al. [Gaitanis, G.; Magiatis, P.; Mexia, N.; Melliou, E.; Efstratiou, MA; Bassukas, ID; Velegraki, A. Antifungal activity of selected Malassezia indolic compounds detected in culture [J]. Mycoses., 2019, 62, 597-603.] found that Malassezia yeasts produce indole alkaloids when grown on L-tryptophan agar. The antifungal test results showed that the tryptanthrin isolated from the fermentation product has moderate anti-dermatophyte activity.

[0010] In 2019, Pedras et al. [Pedras, MSC; Abdoli, A.; To, QH; Thapa, C. Ecological roles of tryptanthrin, indirubin and N-formylanthranilic acid in Isatisindigotica: phytoalexins or phytoanticipins [J]. Chem. Biodivers., 2019, 16, 1800579.] found that after spraying plant indigo produced in China with copper chloride aqueous solution, a metabolite tryptanthrin was produced, which had a stronger growth inhibitory effect on Leptosphaeria maculans than phytoalexincamalexin.

[0011] In 2020, Hesse et al. [Hesse-Macabata, J.; Morgner, B.; Elsner, P.; Hipler, UC; Wiegand, C. Tryptanthrin promotes keratinocyte and fibroblast responses invitro after infection with Trichophyton benhamiae DSM6916 [J]. Sci. Rep., 2020, 10, 1863.] used an in vitro skin ringworm model of fibroblasts and keratinocytes infected with T. benhamiae DSM6916 to analyze the biological activity of tryptanthrin under infection conditions and found that tryptanthrin was almost completely able to prevent the damage of T. benhamiae-derived dermal fibroblasts, significantly reduce the damage of epidermal keratinocytes, and significantly downregulate the expression and secretion of proinflammatory cytokines. The results show that tryptanthrin is not only a strong antifungal drug, but also may regulate innate immune responses.

[0012] In 2022, Leena et al. [Leena, SS; Kaul, G.; Akhir, A.; Saxena, D.; Chopra, S.; Deepthi, A. Green synthesis and antibacterial evaluation of spiro fused tryptanthrin-thiopyrano[2,3-b]indole hybrids targeting drug-resistant S. aureus [J]. Bioorg. Chem., 2022, 128, 106046.] described a green and facile synthesis of 24 tryptanthrin-thiopyrano[2,3-b]indole hybrids, using a heated one-pot multi-component strategy, using the ammonium acetate method under solvent-free conditions at 100°C or the electrochemical method at room temperature. Through in vitro antibacterial activity evaluation, including clinically relevant highly resistant MRSA / VRSA isolates, nitrogen-substituted hybrid molecule compounds were identified to be the most effective against Staphylococcus aureus ATCC 29213 and had a high selectivity index. Further analysis revealed that it had significant concentration-dependent antibacterial activity, a longer post-antibacterial effect (PAE), and could synergize with linezolid against Staphylococcus aureus. Summary of the invention

[0013] One of the objectives of the present invention is to provide a class of 1,8-disubstituted tryptanthrin derivatives.

[0014] Another object of the present invention is to provide a compound and a composition containing the above compound or its isomers, or its salts, or its solvents.

[0015] Another object of the present invention is to provide use of the above compound or the composition.

[0016] Another object of the present invention is to provide a method for controlling bacterial diseases of agricultural plants using the above compounds or the composition.

[0017] Another object of the present invention is to provide the application and research of the above-mentioned compound or the composition in anti-tumor aspects.

[0018] To achieve the above object, the present invention adopts the following technical solutions:

[0019] A class of 1,8-disubstituted tryptanthrin derivatives, wherein the compounds have a structure as shown in the general formula (I):

[0020]

[0021] Wherein, R1 is independently selected from halogen, C1-C4 alkyl, C1-C4 alkoxy, nitro, trifluoromethoxy, trifluoromethyl, amino, hydroxyl, cyano, carboxyl, methylsulfone, and sulfonic acid.

[0022] R2 is a fatty amine, further independently selected from low-carbon fatty amines (C2-C8), higher fatty amines (C8-C22), amino acids and piperazines, including primary amines, secondary amines, tertiary amines, quaternary ammonium salts, and inorganic salts.

[0023] The fatty amines further include morpholine, 1-methylpiperazine, 2-methylpiperazine, ethylpiperazine, cyclopropylpiperazine, amide piperazine derivatives, sulfonamide derivatives, piperazine heterocyclic substituted derivatives, piperidine derivatives, and the like.

[0024] The 1,8-disubstituted tryptanthrin derivatives are selected from the following compounds:

[0025]

[0026]

[0027]

[0028] The present invention also provides a method for preparing the 1,8-disubstituted tryptanthrin derivatives, which comprises the following steps:

[0029]

[0030] The compound or the composition can be used to prevent and control agricultural diseases. Preferably, the agricultural diseases are plant bacterial diseases; more preferably, the agricultural diseases are plant leaf blight, canker and bacterial wilt; most preferably, the agricultural diseases are rice bacterial blight and citrus canker.

[0031] The compound or the composition can also be used for tumor treatment. Preferably, the tumor is leukemia, lung cancer, liver cancer, prostate cancer, colon cancer, cervical cancer; more preferably, the tumor is human tumor cells including human chronic myeloid leukemia, lung cancer, liver cancer and prostate cancer cells.

[0032] The term "halogen" or "halogen atom" refers to fluorine, chlorine, bromine and iodine.

[0033] If not otherwise stated, the compounds of the present invention are understood to include both the free form and the salts thereof. The term "salts" denotes acidic and / or basic salts formed with inorganic and / or organic acids and bases.

[0034] By adopting the above technical scheme, the present invention uses substituted aniline as the starting material, obtains an amide oxime intermediate compound under the action of hydroxylamine hydrochloride, water, trichloroacetaldehyde, and anhydrous sodium sulfate, and heats the ring-closing reaction under the action of concentrated sulfuric acid to obtain a substituted indigo derivative. 4-Fluoroidin is oxidized and rearranged by m-chloroperbenzoic acid in a dichloromethane solvent to obtain 5-fluoroindigo anhydride. 5-Fluoroidin anhydride and the corresponding substituted indigo derivative are reacted by an optimized Bergman reaction to obtain a substituted 1-fluorotryptamine derivative; finally, an excess of the corresponding fatty amine analog is added to the DMF solvent, and the 1,8-disubstituted tryptamine derivative is obtained by heating and stirring. Through the activity test results on plant pathogenic bacteria, it is found that the 1,8-disubstituted tryptamine derivative has a good inhibitory effect on the biological activity of plant pathogens, and has a significant inhibitory effect on rice bacterial blight (Xoo) and citrus canker (Xac). The results of the antiproliferative activity test on tumor cells show that 1,8-disubstituted tryptanthrin derivatives also have good antiproliferative activity, especially when the 8-position is substituted with an electron-withdrawing group, such as 8-fluorotryptanthrin derivatives and 8-nitrotryptanthrin derivatives, which have outstanding performance on tumor cells such as human chronic myeloid leukemia cells K562, human lung cancer cell line A549 and human prostate cancer cell PC3. Based on the natural alkaloid tryptanthrin as the lead compound, the introduction of chain or cyclic fatty amine compounds with good flexibility into the tryptanthrin parent ring structure can effectively enhance the lipid solubility and water solubility of tryptanthrin, and its inhibitory biological activity is also significantly improved, which provides a research direction for the further development of new green, environmentally friendly, efficient and low-toxic pesticides, and also provides a scientific research idea for the research of anti-tumor drugs based on plant alkaloids. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1These are the test results for citrus fruit protection activity. DETAILED DESCRIPTION

[0036] The present invention is further described below by way of examples. It should be understood that the methods described in the examples of the present invention are merely for illustrating the present invention, rather than limiting the present invention, and simple modifications to the preparation methods of the present invention under the premise of the concept of the present invention all belong to the scope of the present invention. All raw materials and solvents used in the examples are commercially available products.

[0037] Example 1

[0038] (1) Preparation of substituted isatin derivatives

[0039] Take a 500mL round-bottom three-necked flask, add 220mL of distilled water, heat to 50°C, add anhydrous sodium sulfate (0.1mol) and stir until completely dissolved. 5% dilute hydrochloric acid completely dissolves the corresponding aniline solution (0.1mol), then add dropwise to the reaction system, continue to add hydroxylamine hydrochloride aqueous solution (0.3mol), heat at 95°C for 5 to 8 hours, follow up with TLC monitoring, wait for the reaction to be complete, cool, vacuum filter, and dry to obtain amide oxime intermediate compound 2.

[0040] Take a 250mL round-bottom three-necked flask, add the corresponding intermediate compound 2 (0.1 mol) in batches into concentrated sulfuric acid, heat and stir at 90°C for 3 to 5 hours, cool to room temperature, add to 500mL of ice-water mixture with rapid stirring, and cyclize for 30min. Filter, wash with water, vacuum filter, and dry to obtain the corresponding substituted indigo derivative of the product.

[0041] (2) Preparation of 5-fluoroindigo carboxylic anhydride

[0042] Take a 250mL round-bottom flask, add 4-fluoroindigo red (10mmol, 1.65g) to 100mL of dichloromethane solvent, add m-chloroperbenzoic acid (12mmol, 2.07g) in batches under ice bath conditions, stir at room temperature for about 5 hours, monitor by TLC until the reaction is complete, filter, wash with saturated sodium bicarbonate, and obtain a white powdery solid through Baeyer-Villiger oxidation rearrangement reaction with a yield of 81.5%.

[0043] (3) Preparation of 1-fluoro-substituted tryptanthrin derivatives

[0044] Take a 150mL round-bottom flask, add the substituted indigo derivative (10mmol) and 4-fluoroindigo anhydride (10mmol, 1.65g) prepared in the above steps into 100mL acetonitrile solvent, respectively, use triethylamine as a catalyst, heat and reflux for 3 to 5 hours, and monitor by TLC. After the reaction is completed, the solvent is dried and separated by column chromatography to obtain 1-fluoro substituted tryptanthrin derivatives with a yield of 51%-73%.

[0045] (4) Preparation of the target compound 1-((3-(dimethylamino)propyl)(methyl)amino)-8-fluoroindole[2,1-b]quinazoline-6,12-dione

[0046] In a 50mL round-bottom flask, 1,8-difluorotryptanthrin (1mmol, 0.28g) and N,N,N'-trimethyl-1,3-propanediamine (3mmol, 0.44mL) were added respectively, heated and stirred at 90°C in N,N-dimethylformamide solvent (DMF, 25mL) for 3 hours, and monitored by TLC until the reaction was complete. The mixture was cooled, and 2.0mL of methanol was added. The mixture was allowed to stand for 30min to precipitate a solid. The solid was vacuum filtered, dried, and separated by column chromatography to obtain 1-((3-(dimethylamino)propyl)(methyl)amino)-8-fluoroindole[2,1-b]quinazoline-6,12-dione with a yield of 75.2%.

[0047] Other 1,8-disubstituted tryptanthrin target compounds are synthesized by using 1-fluoro-substituted tryptanthrin derivatives, corresponding aliphatic amines and other reagent raw materials, referring to the synthesis method of step (4) of the example.

[0048] The structures, H NMR spectra, C NMR spectra and high-resolution mass spectrometry data of some synthesized 1,8-disubstituted tryptanthrin derivatives are shown in Table 1, and the physicochemical properties are shown in Table 2.

[0049] Table 1 1,8-disubstituted tryptanthrin derivatives 1 H NMR, 13 C NMR and ESI-HRMS data

[0050]

[0051]

[0052]

[0053]

[0054]

[0055]

[0056]

[0057]

[0058] Table 2 Physicochemical properties of target compounds

[0059] Table 2 Physicochemical properties of 1,8-disubstituted tryptanthrin derivatives

[0060]

[0061]

[0062] Pharmacological Example 1:

[0063] Tested for resistance to plant pathogens.

[0064] Test method: turbidity method. Test the inhibition rate of 1,8-disubstituted tryptanthrin derivatives against Xanthomonas oryzae (Xoo) and Xanthomonas citri citri (Xac) plant pathogens. The blank control is DMSO, and the positive controls are chlorothalonil and thiabendazole.

[0065] Test steps: Xoo and Xac pathogens were inoculated into solid culture medium (NA) in a constant temperature shaker at 28°C and 180rpm, and cultured in a constant temperature shaker at 28°C / 180rpm until the logarithmic growth phase. The tested compound and positive control drug were prepared with different concentrations of toxic NB liquid culture medium, and 40μL of NB culture medium containing plant pathogens grown to the logarithmic phase was added respectively, and the mixture was shaken in a constant temperature shaker at 28°C / 180rpm. Rice bacterial blight pathogens were cultured for about 36 hours, and kiwifruit canker and citrus canker were cultured for about 48 hours. When the OD value of the control group in the shaker was in the logarithmic growth phase, the OD values ​​of the blank control group, positive control drug and compound were measured at 595nm by an ELISA instrument.

[0066] The calculation formulas for corrected OD value and inhibition rate are as follows:

[0067] Corrected OD value = OD value of bacterial culture medium - OD value of sterile culture medium.

[0068] Inhibition rate % = [(corrected OD value of bacterial solution in control culture medium - corrected OD value of toxic culture medium) / corrected OD value of bacterial solution in control culture medium] × 100.

[0069] The examples of the present invention are used to illustrate the technical solutions of the present invention, but the contents of the examples are not limited thereto. The plant pathogenic bacteria inhibitory activities of the target compounds are shown in Table 3.

[0070] Table 3 Plant pathogenic bacteria inhibitory activity of target compounds

[0071]

[0072]

[0073] BMT is the positive control drug chlorpyrifos, TC is the positive control drug thiophanate-methyl, and the test results are the average of three measurements.

[0074] The above experimental activity data show that the tested 1,8-disubstituted tryptanthrin derivatives have good inhibitory activity against plant pathogenic bacteria. The initial screening inhibitory activity of most compounds at this test concentration is better than that of the positive control compounds chlorothalonil and thiophanate-methyl. They can be used as potential candidate drugs for inhibiting plant pathogenic bacteria and have good research and application value.

[0075] Pharmacological Example 2:

[0076] Citrus fruit protectant activity test.

[0077] Test method: Prepare seasonal citrus fruits, clean the surface of the fruits with sterile water leaves and dry them naturally, and use sterilized syringes to evenly form several circular wounds on the intact surface of each citrus peel. Prepare 20% suspensions of test compound 3 and positive control drug thiophanate-methyl (TC), with drug concentrations of 200 μg / mL, and add an equal amount of DMSO aqueous solution as a blank control. Then, spray the tested aqueous solution evenly on the citrus peel, dry it naturally, place it at a temperature of 28°C, set the light for 16 hours, the dark for 8 hours, and culture it in a light incubator with a humidity of 80% to 90% for 24 hours. Subsequently, the newly activated Xac suspension (OD 595 =0.3) was evenly applied to the wound of the peel slice, and the same culture conditions were cultured in an artificial climate box for 14 days to observe the protective effect of the test drug.

[0078] The results of the citrus fruit protective activity test showed that compound 3 had good protective activity, which was comparable to the protective effect of the positive control drug TC. At a concentration of 200 μg / mL, it had a certain blocking effect on the ulcer spots on the epidermis of citrus fruits, and no obvious scab phenomenon occurred. Therefore, compound 3 may be a small molecule compound with potential to protect citrus fruits and prevent the occurrence of ulcer disease.

[0079] Pharmacological Example 3:

[0080] Antitumor activity testing.

[0081] Test method. MTT method. Take 1g of MTT powder, stir and dissolve in 200mL PBS buffer, filter and sterilize with a 0.22μm filter, divide and seal, and store in a -20℃ refrigerator for later use. Take 23.48g of PBS powder and dissolve in 2000mL ultrapure water, sterilize in an autoclave, filter and sterilize with a 0.22μm filter, divide and seal, and store in a 4℃ refrigerator for later use. Positive control drug, 5-fluorouracil (5-Fu)

[0082] Test steps: Wash the cells in the logarithmic growth phase with pre-cooled PBS, digest with trypsin, centrifuge to remove trypsin, discard the supernatant, add 5 mL of culture medium to resuspend the cells, take 10 μL of cell suspension and place it in a cell counting plate for counting, and calculate the volume of cell suspension and culture medium.

[0083] A negative control group, a positive control group, a blank control group, and an experimental group were set up, with 5 replicate wells in each group. 100 μL of the cell suspension was inoculated in a 96-well plate, with 5,000 cells in each well, and cultured in a constant temperature incubator for 24 h.

[0084] The target compound to be tested was added to a 96-well plate with the corresponding concentration, with 5 replicate wells in each group, and an equal volume of DMSO was added to the negative control group.

[0085] After 48 hours of culture, add 20 μL of MTT solution to each well and continue to culture for 4 hours. For adherent cells, remove the culture medium after 4 hours. For suspended cells, centrifuge at 3500 rpm for 30 minutes after 4 hours and remove the culture medium. Finally, add 150 μL of DMSO to each well, shake on a shaker at 150 rpm for 10 minutes, and measure the absorbance at a wavelength of 490 nm using an enzyme-labeled instrument.

[0086] Inhibition rate % = (1-OD value of the drug-added group-OD value of the blank group / OD value of the negative well-OD value of the blank group) × 100.

[0087] The examples of the present invention are used to illustrate the technical solutions of the present invention, but the contents of the examples are not limited thereto. The anti-proliferative activities of tumor cells of the target compounds are shown in Table 4.

[0088] Table 4 Antiproliferative activity of target compounds on tumor cells

[0089]

[0090]

[0091] 5-Fu is the positive control drug 5-fluorouracil, and the test result is the average of three measurements.

[0092] The above preliminary screening results of anti-tumor activity showed that the tested 1,8-disubstituted tryptanthrin derivatives had a significant inhibitory effect on K562, A549 and PC3 cell lines, which was comparable to the positive control drug 5-Fu. In particular, the inhibitory effects of 8-fluorotryptanthrin derivatives and 8-nitrotryptanthrin derivatives were more significant, and they can be used as potential candidate drugs for inhibiting tumor cell proliferation, which has potential research value and significance.

Claims

1. A class of 1,8-disubstituted tryptanthrin derivatives, characterized in that: The compound has a structure shown by general formula (I): Wherein, R1 is independently selected from halogen, C1-C4 alkyl, C1-C4 alkoxy, nitro, trifluoromethoxy, trifluoromethyl, amino, hydroxyl, cyano, carboxyl, methylsulfone, sulfonic acid; R2 is aliphatic amine.

2. A 1,8-disubstituted tryptanthrin derivative according to claim 1, characterized in that: R1 is independently selected from halogen, C1-C4 alkyl, C1-C4 alkoxy, nitro, trifluoromethoxy, trifluoromethyl, amino, hydroxyl, cyano, carboxyl, methylsulfone, and sulfonic acid; R2 is a fatty amine, independently selected from low-carbon fatty amines (C2-C8) and higher fatty amines (C8-C22), including primary amines, secondary amines, tertiary amines, quaternary ammonium salts, and inorganic salts.

3. A method for preparing a 1,8-disubstituted tryptanthrin derivative according to any one of claims 1 to 2, characterized in that: The following steps are involved:

4. A composition characterized by: A composition comprising the derivative according to any one of claims 1 to 2, as well as an adjuvant or bactericidal preparation for use in agriculture, and an anti-tumor agent for use in medicine.

5. Use of the derivative according to any one of claims 1 to 2 or the composition according to claim 4 in the preparation of drugs against agricultural pathogens and diseases and in the preparation of anti-tumor drugs.

6. The use according to claim 5, characterized in that: The pathogenic bacteria and diseases are plant pathogenic bacteria diseases.

7. The use according to claim 6, characterized in that: The plant pathogens are Xanthomonas oryzae pv. oryzae, Xoo, and Xanthomonas campestris pv. citri, Xac.

8. The use according to claim 5, characterized in that: The tumors include human chronic myeloid leukemia cells K562, human lung cancer cell line A549, human liver cancer cells HepG2 and human prostate cancer cells PC3.

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