2-fluoro-3-aliphatic amine tryptanthrin derivative as well as preparation method and application thereof

Abstract

The invention discloses a 2-fluoro-3-aliphatic amine tryptanthrin derivative and application of the compound to prevention and treatment of phytopathogen and anti-tumor activity, the general formula of the derivative is as shown in (I), and the test result of the compound as shown in the general formula to the bacterial activity of phytopathogen shows that the compound can be used for preparing the 2-fluoro-3-aliphatic amine tryptanthrin derivative. The compound has a good antibacterial effect on Xanthomonas oryzae pv. Oryzae, Xanthomonas citri pv. Citri and the like, and 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 2-fluoro-3-fatty amine tryptanthrin derivatives and their application in antibacterial activity and anti-tumor research. Background Art

[0002] Indolequinazoline alkaloids, such as tryptanthrin, (new) spatholobi alkaloids, camelinine A alkaloids, and evodia rutaecarpa (secondary) alkaloids, have a wide range of biological activities and structural diversity. They are also an important supplement to the current screening library of synthetic compounds. The efficacy, selectivity and pharmacokinetics of bioactive natural products are improved through structural modification, which makes these special skeletons play an important role in the process of finding new candidate drugs. Radix Isatidis is the dried root of Isatis indigotica Fort., a cruciferous plant, and Folium isatidis is the dried leaf of Isatis indigotica. Both are cold in nature and bitter in taste. They have the effects of clearing away heat and detoxifying, killing bacteria and reducing inflammation, and cooling blood and relieving throat pain. They are often used to enhance the body's immunity, antibacterial, antiviral, and anti-tumor effects. A large number of literature reports on the chemical composition and activity of Radix Isatidis have been published at home and abroad, including quinazolinone alkaloids, indole alkaloids, lignan compounds, organic acid compounds, flavonoids and glycoside compounds. The active small molecule compounds of indolequinazoline alkaloids are used as the lead discovery, and the design, synthesis and structural optimization are now the hot spots in drug development research.

[0003] Tryptanthrins and their analogs, such as Phaitanthrins AE, Methylisatoid, Candidine, Cephalanthrin AB, Ophiuroidin, and (±)-Cruciferane, are a class of indolo[2,1-b]quinazoline-6,12-dione alkaloids isolated from natural plants and different cell cultures. These compounds have attracted great interest as potential therapeutic drugs due to their wide range of biological and pharmaceutical activities, including antitumor, antiparasitic, antibacterial, anti-inflammatory, antimalarial, antiviral, and antituberculosis activities.

[0004] As the biological isostere of hydrogen atoms, fluorine atoms play an important role in the development and application of natural fluorinated alkaloids. The introduction of fluorine atoms can not only maintain and improve biological activity, but also further reduce toxic side effects. Fluorine atoms have unique physical and chemical properties. The spatial parameters of hydrogen and fluorine are similar, and the van der Waals radii are and Although fluorine has a slightly larger radius than hydrogen, its van der Waals radius is closer to oxygen. Fluorine can effectively replace lone pairs of electrons, hydrogen atoms, and oxygen atoms, affecting the efficacy, conformation, metabolism, membrane permeability, and P-glycoprotein recognition of molecules, maintaining equivalent or even better biological activity. Replacing hydrogen atoms with fluorine can increase the physical size, moderately increase the lipophilicity of the molecule (the π coefficient of the C-F bond is 0.14), significantly increase the molecular weight of the target compound, and greatly improve its stability and bioavailability in the body.

[0005] As an important component of alkaloids, nitrogen atoms play a key role in the mutual binding with various targets in the body, and are also an important means to obtain new derivatives and improve biological activity. Fatty amine compounds themselves are a class of substructural units and bridging groups with broad biological activity, which can effectively improve and regulate the water solubility and fat solubility of compounds, and are widely used in effectively linking substructural active units.

[0006] In 1971, Schindler et al [Schindler, F.; H. Metabolic products of microorganisms. 91. Tryptanthrin, a tryptophan derived antibiotic from Candidalipolytica [J]. Arch. Mikrobiol., 1971, 79, 187-203.] A compound was isolated from the metabolites of the microorganism Candida lipolytica after fermentation in a culture medium with excess tryptophan. This is also the earliest origin of the name tryptanthrin.

[0007] In 1979, Honda et al. [Honda, G.; Tabata, M. Isolation of antifungal principle tryptanthrin, from Strobilanthes cusia O. Kuntze [J]. Planta Med., 1979, 36, 85-90.] isolated tryptanthrin from the leaves of Strobilanthes cusia produced in Okinawa Island in a folk remedy for treating athlete's foot, and found that it had strong antifungal activity against skin fungi.

[0008] In 1980, Honda et al. [Honda, G.; Tosirisuk, V.; Tabata, M. Isolation of anantidermatophytic, tryptanthrin, from indigo plants, Polygonum tinctorium and Isatis tinc-toria [J]. Planta Med., 1980, 38, 275-276] isolated a tryptanthrin compound that is effective against skin fungal diseases from indigo plants such as Polygonum tinctorium and Isatis tinctoria.

[0009] In 1998, Yoshikawa et al. [Yoshikawa, M.; Murakami, T.; Kishi, A.; Sakurama, T.; Matsuda, H.; Nomura, M.; Matsuda, H.; Kubo, M. Novel indole S, O-bisdesmoside, calanthoside, the precursor glycoside of tryptanthrin, indirubin, and isatin, with increasing skin blood flow promoting effects, from two Calanthe species (Orchidaceae) [J]. Chem. Pharm. Bull (Tokyo)., 1998, 46, 886-888.] isolated an indole glycoside compound (Calanthoside) from two plants, Calanthe discolor and C. liukiuensis, and the β-glucosidase hydrolysis product was separated to obtain tryptanthrin.

[0010] In 1999, Hosoe et al [Hosoe, T.; Nozawa, K.; Kawahara, N.; Fukushima, K.;

[0011] Nishimura, K.; Miyaji, M.; Kawai, K. Isolation of a new potent cytotoxic pigment along with indigotin from the pathogenic basidiomycetous fungus Schizophyllum commune [J]. Mycopathologia., 1999, 146, 9-12.] Tryptanthrin compounds were isolated from the culture fluid of Schizophyllum commune isolated from patients with allergic bronchopulmonary fungal disease.

[0012] In 2000, Li Bin et al. [Li Bin, Chen Wansheng, Zheng Shuiqing, Yang Genjin, Qiao Chuanzhuo. Two new alkaloids from tetraploid Isatis root [J]. Acta Pharmaceutica Sinica, 2000, 35, 508-510.] separated and purified the chemical components in the ethyl acetate extraction part to obtain tryptanthrin compounds while studying the chemical components in tetraploid Isatis root.

[0013] In 2005, Ruan Jinlan et al. [Ruan Jinlan, Zou Jianhua, Cai Yaling. Research on chemical components of Isatis indigotica [J]. Chinese Journal of Traditional Chinese Medicine, 2005, 30, 1525-1526.] isolated tryptanthrin from Isatis indigotica for the first time when studying the chemical components of the total ethanol extract of Isatis indigotica.

[0014] In 2018, Liu Yanyan et al. [Liu Yanyan, Shen Xinqian, Wang Xiaozheng, Lin Shuangjun. 2-Indole alkaloids synthesized by marine Streptomyces Streptomyces sp. B9173 [J]. Bulletin of Microbiology, 2018, 45, 2470-2479.] isolated and purified the secondary metabolites of marine Streptomyces (Streptomyces sp., B9173) obtained from sediments in Chile along the Pacific coast, and obtained tryptanthrin compounds in this bacterium for the first time.

[0015] 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.

[0016] In 2022, Palabindela et al. [Palabindela, R.; Guda, R.; Ramesh, G.; Myadaraveni. P.; Banothu, D.; Ravi, G.; | Korra, R.; Mekala, H.; Kasula, M. Novel tryptanthrin hybrids bearing aminothiazoles as potential EGFR inhibitors: Design, synthesis, biological screening, molecular docking studies, and ADME / T predictions [J]. J. Heterocyclic Chem., 2022, 59, 1533-1550.] used different α-bromo-4-substituted acetophenones and thiosemicarbazide compounds as raw materials to synthesize novel tryptanthrin aminothiazole analogs with antitumor active thiazole groups. All compounds were evaluated for their in vitro anticancer activity against three human cancer cells (MCF-7, A549 and HeLa) using cisplatin as the control drug, and some compounds showed good antitumor activity. Molecular docking studies targeting EGFR showed that the tryptanthiazole analogue had better binding energy than EGFR inhibitors (gefitinib, erlotinib and lapatinib). In computer ADME / T prediction evaluation, the analogue also had good pharmacokinetic characteristics. Summary of the invention

[0017] One of the purposes of the present invention is to provide a class of 2-fluoro-3-aliphatic amine tryptanthrin derivatives.

[0018] 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.

[0019] Another object of the present invention is to provide use of the above compound or the composition.

[0020] 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.

[0021] 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.

[0022] To achieve the above object, the present invention adopts the following technical solutions:

[0023] A class of 2-fluoro-3-fatty amine tryptanthrin derivatives, wherein the compounds have a structure as shown in the general formula (I):

[0024]

[0025] Wherein, R1 is independently selected from hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, nitro, trifluoromethoxy, trifluoromethyl, amino, hydroxyl, cyano, carboxyl, methylsulfone, and sulfonic acid.

[0026] R2 is a fatty amine, further independently selected from low-carbon fatty amines (C2-C8), higher fatty amines (C9-C22), amino acids and piperazines, including primary amines, secondary amines, tertiary amines, quaternary ammonium salts, and inorganic salts.

[0027] The fatty amines further include morpholine, 1-methylpiperazine, 2-methylpiperazine, piperazine ester derivatives, piperazine alcohol derivatives, piperazine carboxylic acid derivatives, amide derivatives, sulfonamide derivatives, piperazine heterocyclic substituted derivatives, piperidine derivatives, and the like.

[0028] The 2-fluoro-3-fatty amine tryptanthrin derivatives are selected from the following compounds:

[0029]

[0030]

[0031]

[0032] The present invention also provides a method for preparing the 2-fluoro-3-fatty amine tryptanthrin derivatives, which comprises the following steps:

[0033]

[0034] 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.

[0035] 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. Most preferably, the tumor cell line is human chronic myeloid leukemia cell K562, human lung cancer cell line A549, and human prostate cancer cell line PC3.

[0036] The term "halogen" or "halogen atom" refers to fluorine, chlorine, bromine and iodine.

[0037] 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.

[0038] Beneficial effects of the present invention: By adopting the above technical scheme, the present invention uses substituted aniline as the starting material, and obtains an amide oxime intermediate compound under the action of hydroxylamine hydrochloride, water, trichloroacetaldehyde, and anhydrous sodium sulfate. Then, a ring-closing reaction is performed under the action of concentrated sulfuric acid to obtain a substituted indigo derivative. 5,6-difluoro indigo in a dichloromethane solvent is subjected to an oxidative rearrangement reaction of meta-chloroperbenzoic acid to obtain 6,7-difluoro indigo anhydride. 6,7-difluoro indigo anhydride reacts with the corresponding substituted indigo derivative under optimized conditions to obtain a 2,3-difluoro tryptanthrin derivative; finally, an excess of the corresponding fatty amine analog is added to the DMF solvent, heated and stirred, and purified by column chromatography to obtain a 2-fluoro-3-fatty amine tryptanthrin derivative. The activity test results on plant pathogenic bacteria show that the 2-fluoro-3-fatty amine tryptanthrin derivative has good inhibitory activity on 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 showed that 2-fluoro-3-aliphatic amine tryptanthrin derivatives also have good antiproliferative activity, especially the 8-halogen atom and nitro-substituted tryptanthrin derivatives have obvious antiproliferative activity on tumor cells K562, A549 and PC3. Taking the natural alkaloid tryptanthrin as the guide, the introduction of chain and cyclic fatty amine analogs enhances the fat solubility and water solubility of tryptanthrin derivatives, significantly improves their biological activity, and provides a research direction for further exploring new green, efficient and low-toxic pesticides, and also provides a scientific research idea for the research of plant-derived alkaloid antitumor drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 These are the test results for the protective activity of citrus leaves. DETAILED DESCRIPTION

[0040] 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.

[0041] Example 1

[0042] (1) Preparation of substituted isatin derivatives

[0043] Take a 500mL round-bottom three-necked flask, add 220mL distilled water, heat to 50°C, continue to add anhydrous sodium sulfate (0.1mol) and stir until completely dissolved. Use 5% dilute hydrochloric acid to completely dissolve the corresponding aniline solution (0.1mol), add it drop by drop 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, wait for the reaction to be complete, cool, vacuum filter, and dry to obtain amide oxime intermediate compound 2.

[0044] 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, and vacuum dry to obtain the corresponding substituted indigo derivative.

[0045] (2) Preparation of 6,7-difluoroindigo carboxylic anhydride

[0046] Take a 250mL round-bottom flask, add 5,6-difluoroindigo 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, dry in vacuo, and purify by column chromatography to obtain a white solid with a yield of 71.3%.

[0047] (3) Preparation of 2,3-difluorotryptamine derivatives

[0048] Take a 150mL round-bottom flask, add the substituted indigo derivative (10mmol) and 6,7-difluoroindigo 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, monitor by TLC until the reaction is complete, spin dry the solvent, and purify by column chromatography to obtain 2,3-difluorotryptamine derivatives with a yield of 41%-68%.

[0049] (4) Preparation of the target compound 3-((3-(dimethylamino)propyl)(methyl)amino)-2,8-difluoroindole[2,1-b]quinazoline-6,12-dione

[0050] In a 50mL round-bottom flask, 2,3,8-trifluorotryptanthrin (1mmol, 0.30g) and N,N,N'-trimethyl-1,3-propanediamine (3mmol, 0.35g) were added respectively, heated and stirred at 50°C in N,N-dimethylformamide solvent (DMF, 25mL) for 2 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 3-((3-(dimethylamino)propyl)(methyl)amino)-2,8-difluoroindole[2,1-b]quinazoline-6,12-dione with a yield of 57.9%.

[0051] Other 2-fluoro-3-aliphatic amine tryptanthrin derivatives are prepared by using 2,3-difluorotryptanthrin derivatives, corresponding aliphatic amines and other reagent raw materials, and referring to the synthesis method of step (4) of the example.

[0052] The structures, H NMR spectra, C NMR spectra and high-resolution mass spectrometry data of some 2-fluoro-3-aliphatic amine tryptanthrin derivatives are shown in Table 1, and the physicochemical properties are shown in Table 2.

[0053] Table 1 2-Fluoro-3-aliphatic amine tryptanthrin derivatives 1 H NMR, 13 C NMR and ESI-HRMS data

[0054]

[0055]

[0056]

[0057]

[0058]

[0059]

[0060]

[0061]

[0062]

[0063]

[0064] Table 2 Physicochemical properties of target compounds

[0065] Table 2 Physicochemical properties of 2-fluoro-3-aliphatic amine tryptanthrin derivatives

[0066]

[0067]

[0068] Pharmacological Example 1:

[0069] Testing for resistance to plant pathogens.

[0070] Test method: turbidity method. Test the inhibition rate of 2-fluoro-3-aliphatic amine tryptanthrin derivatives on rice bacterial blight (Xoo) and citrus canker (Xac) plant pathogens. The blank control is DMSO, and the positive controls are chlorothalonil and thiophanate-methyl.

[0071] Test steps: The constant temperature shaker is controlled at 28℃ and 180rpm. Xoo and Xac pathogens are inoculated into NB medium and cultured to the logarithmic phase for use. The tested compound and the positive control drug are prepared with different concentrations of toxic NB liquid culture medium, and 40μL of NB culture medium containing plant pathogens in the logarithmic phase is added respectively. The mixture is shaken in a constant temperature shaker at 28℃ / 180rpm. The rice bacterial leaf blight pathogen is cultured for about 36 hours, and the citrus canker pathogen is cultured for about 48 hours. The OD value of the blank control group in the shaker is 0.04. 595 When the cells were in the logarithmic growth phase, the OD values ​​of the blank control group, the positive control drug and the compound were measured at 595 nm using an enzyme marker.

[0072] The calculation formulas for corrected OD value and inhibition rate are as follows:

[0073] Corrected OD value = OD value of bacterial culture medium - OD value of sterile culture medium.

[0074] 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.

[0075] 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.

[0076] Table 3 Plant pathogenic bacteria inhibitory activity of target compounds

[0077]

[0078]

[0079] 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.

[0080] The above experimental activity data show that the tested 2-fluoro-3-aliphatic amine tryptanthrin derivatives have good antibacterial activity against plant pathogenic bacteria. The initial screening inhibitory activity of most target 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 development value.

[0081] Pharmacological Example 2:

[0082] Citrus leaf protective activity test.

[0083] Test method: prepare potted citrus plants, clean the citrus leaves with sterile water and dry them naturally, and use a sterilized syringe to evenly form several circular wounds in the middle of each citrus leaf. Prepare 20% suspensions of test compound 1 and positive control drug copper thiazole (TC), with drug concentrations of 200 μg / mL, and add an equal amount of DMSO aqueous solution as a blank control. Then, spray the test drug aqueous solution evenly on the citrus leaves, dry them naturally, place them at a temperature of 28°C, set the light for 16 hours, the dark for 8 hours, and culture them in a light incubator with a humidity of 80% to 95% for 24 hours. Subsequently, the newly activated Xac suspension (OD 595 =0.5) was evenly applied to the wound of the leaves and cultured in an artificial climate box under the same culture conditions for 14 days to observe the protective effect of the test drug.

[0084] The results of the protective activity test on citrus leaves showed that compound 1 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 relatively significant blocking effect on the expansion of citrus leaf ulcers, and no obvious scabs appeared at some wounds. Therefore, compound 1 may be a potential candidate drug for protecting citrus leaves from infection with citrus canker bacteria.

[0085] Pharmacological Example 3:

[0086] Antitumor activity testing.

[0087] 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)

[0088] 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.

[0089] 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.

[0090] 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.

[0091] 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.

[0092] 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.

[0093] 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 the target compounds on tumor cells are shown in Table 4.

[0094] Table 4 Antiproliferative activity of target compounds on tumor cells

[0095]

[0096]

[0097] 5-Fu is the positive control drug 5-fluorouracil, and the test result is the average of three measurements.

[0098] The preliminary screening results of the above anti-tumor activity showed that the tested 2-fluoro-3-aliphatic amine tryptanthrin derivatives had a more obvious inhibitory effect on K562, A549 and PC3 cell lines, especially the tryptanthrin derivatives substituted with halogen atoms and nitro groups at the 8th position had an anti-proliferation effect comparable to that of the positive control drug 5-Fu, and could be used as potential candidate drugs for inhibiting tumor cell proliferation, with potential research value and significance.

Claims

1. A 2-fluoro-3-fatty amine tryptanthrin derivative, characterized in that: The compound has a structure shown by general formula (I): Wherein, R1 is independently selected from hydrogen, halogen, C1-C4 alkane, C1-C4 alkoxy, nitro, trifluoromethoxy, trifluoromethyl, amino, hydroxyl, cyano, carboxyl, methylsulfone, sulfonic acid; R2 is a fatty amine.

2. The 2-fluoro-3-fatty amine tryptanthrin derivative according to claim 1, characterized in that: R1 is independently selected from hydrogen, halogen, C1-C4 alkyl, C1-C4 alkoxy, nitro, trifluoromethoxy, trifluoromethyl, amino, hydroxyl, cyano, carboxyl, methylsulfone, and sulfonic acid; R2 is independently selected from C2-C8 fatty amines and C9-C22 higher fatty amines, including primary amines, secondary amines, tertiary amines, quaternary ammonium salts, and inorganic salts.

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

4. A composition characterized by: Contains the derivative according to any one of claims 1 to 2, and an agricultural adjuvant or fungicide.

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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