Aliphatic amine polysubstituted tryptanthrin derivative as well as preparation method and application thereof

Abstract

The invention discloses an aliphatic amine polysubstituted tryptanthrin derivative and a preparation method and application thereof, the general formula of the derivative is shown as (I), X2, X4, Y2 and Y4 are hydrogen or halogen, and R1, R2, R3 and R4 are polysubstituted aliphatic amine. According to the application of the derivative to prevention and treatment of phytopathogen bacteria, the test result of the activity of the phytopathogen bacteria shows that the derivative has a relatively good antibacterial effect on xanthomonas oryzae pv. Oryzae, rice bacterial streak, citrus canker, kiwifruit canker and the like, and can be used for developing novel efficient agricultural bactericides.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of fine chemical industry, and particularly relates to a preparation method of a class of fatty amine polysubstituted tryptanthrin derivatives and application thereof in antibacterial activity research. BACKGROUND

[0002] Tryptanthrin is a natural alkaloid with indole quinazoline skeleton, which is widely present in various medicinal plants and microorganisms. Since this class of compounds was isolated and identified from indigo plants in the 1970s, due to its unique chemical structure and significant biological activity, it has gradually become an important direction in the field of natural product research. Traditional Chinese medicinal materials such as Banlangen have been used for a long time in the experience application of anti-inflammatory and antiviral treatment, which provides an important clue for the modern research of tryptanthrin compounds. In recent years, with the development of natural product separation and identification technology, more and more tryptanthrin analogues have been found from different biological resources, and the diversity of their chemical structure and pharmacological activity has opened up broad prospects for the development of innovative drugs. Tryptanthrin and analogues, such as Phaitanthrins A-E, Methylisatoid, Candidine, Cephalanthrin A-B, Ophiuroidin and (±)-Cruciferane, are a class of indole[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 pharmacological activities, including anti-tumor, anti-parasite, anti-bacterial, anti-inflammatory, anti-malarial, anti-viral, and anti-tuberculosis activities.

[0003] The research on tryptanthrin and its derivatives has important significance in many aspects. From the chemical structure, tryptanthrin molecule contains multiple modification sites, and the introduction of functional groups at positions 1, 3, 6, 7, 9, etc. can significantly improve its physicochemical properties and bioavailability. A large number of structure modification studies have shown that different substituents have a decisive influence on the activity of the compounds. In terms of biological activity, tryptanthrin compounds exhibit a wide range of pharmacological effects: they exert anti-tumor effect by regulating the NF-κB and Wnt / β-catenin signaling pathways; achieve anti-inflammatory effect by inhibiting the expression of inflammatory-related factors TNF-α and iNOS; and also have significant antimicrobial, antioxidant and neuroprotective activities. More notably, these compounds usually exhibit low cytotoxicity, which makes it possible for their safe application in clinical practice. From the perspective of natural drug development, tryptanthrin alkaloids are not only the research object of modernization of traditional Chinese medicine, but also provide important lead compounds for the design and development of new multi-target drugs.

[0004] Aliphatic amines and their derivatives play an important role in drug development due to their structural tunability, biocompatibility, and diverse pharmacological activities. They have applications in various fields such as antibacterial agents, antiviral drugs, antitumor drugs, neurotransmitter modulators, and drug delivery systems. They are a class of organic compounds with amino and hydrophobic alkyl chains. Depending on the substituents on the nitrogen atom, they can be classified as primary amines (1°), secondary amines (2°), tertiary amines (3°), and quaternary ammonium salts (4°). These compounds exhibit significant activity in bactericidal and antibacterial applications due to the presence of both hydrophilic amino groups and hydrophobic carbon chains. They are widely used in medical disinfection, agricultural fungicides, and daily hygiene preservation. At the same time, aliphatic amine compounds are a class of substructure units and bridging groups with broad biological activity, which can effectively improve and regulate the water solubility and lipophilicity of compounds, and are widely used in linking active substructure units.

[0005] In 2019, Schepetkin et al. designed and synthesized a new class of 11H-indolo[1,2-b]quinoxalin-11-one oxime analogs and tryptanthrin-6-oxime, and evaluated their effects on JNK activity. Several compounds showed sub-micromolar JNK binding affinity and selectivity for JNK1 / JNK3 and JNK2. Among them, tryptanthrin-6-oxime had dissociation constants (Kd) of 22 and 76 nanomolar for JNK1 and JNK3, respectively, and 150 and 275 nanomolar for JNK2. Molecular modeling showed that the binding mode at the JNK catalytic site was a competitive JNK inhibitor, and the binding activity was related to its ability to inhibit nuclear factor-kappa B / activator protein 1 (NF-κB / AP-1) activation in lipopolysaccharide (LPS)-induced human monocyte THP-1 Blue cells and interleukin-6 (IL-6) production in human MonoMac-6 cells. Therefore, these compounds can be used as specific small molecule modulators for JNK mechanism research and potential lead compounds for anti-inflammatory drug development.

[0006] In 2020, Hao et al. first discovered that tryptophan ketone compounds had good antiviral activity against tobacco mosaic virus (TMV). The anti-TMV activity of most tryptophan ketone compounds was higher than that of ribavirin (inhibition rates of 40%, 37%, and 38% for in vivo inactivation, treatment, and protection activities, respectively). Compound a (inhibition rates of 52%, 49%, and 54% for in vivo inactivation, treatment, and protection activities, respectively) and compound b (inhibition rates of 51%, 48%, and 53% for in vivo inactivation, treatment, and protection activities, respectively) became new antiviral lead compounds with excellent antiviral activity. Compound c was selected for further antiviral mechanism research, which can inhibit virus assembly by decomposing the 20S capsid protein (CP) disc. Bactericidal activity tests showed that tryptophan ketone exhibited broad-spectrum bactericidal activity and good selectivity against Venturia inaequalis, further broadening the biological activity spectrum of tryptophan ketone derivatives and laying a foundation for their application in plant protection.

[0007] In 2021, Hou et al. developed a method for efficiently and conveniently synthesizing tryptophan ketone derivatives, which can rapidly prepare N-substituted tryptophan ketone analogs through the reaction of tryptophan ketone with secondary amines under mild reaction conditions. All compounds were tested for antitumor activity in cancer cell lines by MTT assay. The results showed that some of the compounds had antitumor activity against human tumor cell lines A549, HCT116, and MDA-MB-231, with an average half-maximal inhibitory concentration (IC 50 ) at low micromolar levels and the ability to dose-dependently induce G2 / S phase cell cycle arrest and apoptosis in A549 cells.

[0008] In 2022, Sudheendran Leena et al. published a simple and green synthesis method for synthesizing 24 tryptophan ketone hybrid molecules. The method uses a thermal one-pot multi-component strategy under solvent-free conditions at 100°C with ammonium acetate and at room temperature through an electrochemical method. The in vitro antibacterial activity of the compounds was evaluated, including clinically relevant high drug-resistant Staphylococcus aureus (MRSA / VRSA) isolates. The results showed that nitro-substituted hybrid molecules had the strongest antibacterial activity against Staphylococcus aureus ATCC 29213 and a high selectivity index. Further analysis showed that they also had concentration-dependent bactericidal activity, a long post-antibiotic effect (PAE), and synergistic effects with linezolid against Staphylococcus aureus, making them promising as a new type of Staphylococcus aureus treatment drug.

[0009] In 2023, inspired by the development and application of natural product fungicides, Zhang et al. designed and synthesized a series of novel 9-aliphatic amine tryptamine derivatives and evaluated their bioactivity against three plant bacteria. Most of them exhibited excellent antibacterial activity in vitro. Among them, some compounds showed significantly better inhibitory effects against *Xac. citrus canker*, *Xoo. citrus bacterial blight*, and *Psa. kiwifruit canker* than the commercially available pesticide thiabendazole copper, with EC50... 50 The values ​​were 0.769, 1.29, and 15.5 μg / mL, respectively, while those of thiabendazole copper were 58.8, 70.9, and 91.9 μg / mL. Mechanistic studies showed that these compounds could alter bacterial morphology, induce reactive oxygen species accumulation, promote bacterial apoptosis, inhibit normal cell growth, and affect cell membrane permeability. Furthermore, in vivo experiments also confirmed their therapeutic and preventative effects against citrus canker. Proteomic analysis revealed that the main differences lay in the bacterial secretion system pathway, which hindered membrane transport.

[0010] In 2024, Xia et al. designed and synthesized two series of novel tryptophan derivatives as multifunctional drugs for the treatment of Alzheimer's disease (AD). Inhibition experiments on cholinesterase (ChE) showed that these derivatives can act as inhibitors of acetylcholinesterase (AChE) and are selective for butyrylcholinesterase (BuChE). Among them, the target compound exhibited the best cholinesterase inhibitory activity (AChE, IC50). 50 =12.17±1.50nM; BuChE, IC 50 =6.29±0.48 μM). Simultaneously, it exhibits appropriate blood-brain barrier permeability in parallel artificial membrane permeability assays. In vivo studies have shown that it can effectively improve learning and memory impairments in a scopolamine-induced Alzheimer's disease mouse model. Nissl staining of mouse hippocampal tissue sections showed the ability to restore neurons in the CA3 and CA1 regions of the hippocampus. These findings suggest that it may be a promising candidate compound for further development into a multifunctional drug for the treatment of Alzheimer's disease.

[0011] In 2025, Zhu et al. synthesized a series of 7-piperazine thiocarbonate tryptophan derivatives, among which the T7NHCO series compounds showed significant antibacterial activity against *Rhizoctonia solani*, *Actinidia chinensis*, and *Rhizoctonia solani*, with half-inhibitory concentrations (EC50) reaching [value missing]. 50 The concentrations ranged from 0.26 to 0.56 μg / mL, while exhibiting low cytotoxicity against normal HEK-293 cells. These compounds inhibited biofilm formation, disrupted bacterial morphology, downregulated the expression of bacterial chemotaxis-related proteins, leading to bacterial necrosis, and effectively controlled citrus and kiwi fruit canker diseases, with therapeutic and preventative efficiencies of 79.35% and 88.31%, respectively. Summary of the Invention

[0012] One of the objectives of this invention is to provide a class of fatty amine polysubstituted tryptamine ketone derivatives.

[0013] Another object of the present invention is to provide a compound or its isomer, its salt, or its solvent compound and composition containing the above-mentioned compound or its isomer, its salt, or its solvent.

[0014] Another object of the present invention is to provide the use of the above-described compound or the composition.

[0015] Another object of the present invention is to provide a method for controlling bacterial diseases of agricultural plants using the above-mentioned compounds or compositions.

[0016] To achieve the above objectives, the present invention adopts the following technical solution:

[0017] A class of fatty amine polysubstituted tryptophanone derivatives, which have structures as shown in general formula (I):

[0018]

[0019] X2, X4, Y2, and Y4 are hydrogen or halogens, and the halogens are further independently selected from fluorine, chlorine, bromine, iodine monosubstituted, polysubstituted, or combined halogen substituted compounds. R1, R2, R3, and R4 are polysubstituted aliphatic amines, which include disubstituted, trisubstituted, and tetrasubstituted aliphatic amines or different aliphatic amine compounds.

[0020] The fatty amines are 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.

[0021] The aforementioned fatty amines further include morpholine, piperazine, 1-methylpiperazine, 2-methylpiperazine, ethylpiperazine, cyclopropylpiperazine, amide-piperazine derivatives, sulfonamide derivatives, piperazine heterocyclic substituted derivatives, piperidine derivatives, and N... 1 N 1 N 3 -Trimethyl-1,3-propanediamine, N 1 N 1 N 2 -Trimethylethane-1,2-diamine, etc.

[0022] The aforementioned class of fatty amine polysubstituted tryptophanone derivatives are selected from the following compounds:

[0023]

[0024]

[0025]

[0026] The present invention also provides a method for preparing the aforementioned class of fatty amine polysubstituted tryptophan ketone derivatives, comprising the following steps:

[0027]

[0028] The compound or composition described herein can be used to prevent and control agricultural diseases. Preferably, the agricultural diseases are bacterial plant diseases; more preferably, the agricultural diseases are leaf blight, leaf streak, and canker of cereal plants; most preferably, the agricultural diseases are bacterial leaf blight of rice, bacterial leaf streak of rice, canker of citrus, and canker of kiwifruit.

[0029] The term "halogen" or "halogen atom" refers to fluorine, chlorine, bromine, and iodine.

[0030] Unless otherwise stated, the compounds of this invention are understood to include both their free state and their salts. The term "salt" means an acidic and / or basic salt formed from inorganic and / or organic acids and bases.

[0031] By employing the above technical solution, this invention uses halogenated aniline as a starting material to obtain an amidoxime intermediate compound under the action of hydroxylamine hydrochloride, water, trichloroacetaldehyde, and anhydrous sodium sulfate. A cyclization reaction is then carried out under concentrated sulfuric acid to obtain a halogenated indigo derivative. The halogenated indigo is then reacted with m-chloroperoxybenzoic acid in dichloromethane solvent to obtain halogenated indigo anhydride. The halogenated indigo anhydride reacts with the corresponding indigo derivative through an optimized Bergman cyclization reaction to obtain a halogenated tryptamine ketone derivative. Finally, an excess of the corresponding aliphatic amine compound is added to DMF solvent, and the mixture is heated and stirred to obtain a fatty amine polysubstituted tryptamine ketone derivative. Activity tests on plant pathogenic bacteria show that the fatty amine polysubstituted tryptamine ketone derivative exhibits good inhibitory activity against plant pathogens. Among them, compounds 3, 4, 22, 23, 28, 29, 30, and 33 showed inhibitory effects against rice bacterial leaf blight (Xoo) and rice bacterial leaf streak (Xoc). Compounds 3, 9, 22, 29, 30, 33, 35, and 36 showed greater inhibitory effects against citrus canker (Xac) and kiwifruit canker (Psa) than the positive control agents tebuconazole and thiamethoxam. Compounds 16 and 17 selectively inhibited Xoc, compounds 6 and 7 selectively inhibited Xac, and compounds 16 and 39 also showed significant selective inhibition of Psa. Compounds 3, 22, 29, 30, and 33 exhibited strong broad-spectrum inhibitory effects against all four bacterial strains. Using the natural alkaloid tryptophanone as the lead structure, more flexible chain or cyclic aliphatic amine compounds are introduced into the tryptophanone parent ring structure, which further enhances the lipid solubility and water solubility of tryptophanone derivatives. Its antibacterial activity is also significantly improved, and it can be further developed into a novel pesticide fungicide with high efficiency and low toxicity. Attached Figure Description

[0032] Appendix Figure 1 The image shows the results of the protective activity test against bacterial blight in rice. Detailed Implementation

[0033] The present invention will be further illustrated below through examples. It should be understood that the methods described in the examples are merely illustrative and not intended to limit the invention. Simple modifications to the preparation methods of the present invention within the framework of the present invention's concept are all within the scope of the invention. All raw materials and solvents used in the examples are commercially available products of analytical purity.

[0034] Example 1

[0035] (1) Preparation of halogenated indigo derivatives

[0036] Take a 500 mL round-bottom three-necked flask, add 220 mL of distilled water, heat to 50 °C, add anhydrous sodium sulfate (0.1 mol) and stir until completely dissolved. Dissolve the corresponding halogenated aniline compound 1 solution (0.1 mol) completely in 5% dilute hydrochloric acid, then add it dropwise to the reaction system. Continue to add hydroxylamine hydrochloride aqueous solution (0.3 mol). Heat at 95 °C for 5 to 8 hours, monitor with TLC. After the reaction is complete, cool, vacuum filter, and dry to obtain the amidine oxime intermediate compound 2.

[0037] Take a 250mL round-bottom three-necked flask, add the corresponding intermediate compound 2 (0.1mol) in batches to concentrated sulfuric acid, heat and stir at 90℃ for 3 to 5 hours, cool to room temperature, add to 500mL ice-water mixture with rapid stirring, cyclize for 30min, filter, wash with water, vacuum filter, dry, and obtain the corresponding substituted halogenated indigo derivative 3.

[0038] (2) Preparation of halogenated indigo anhydride

[0039] Take a 250 mL round-bottom flask and add 10 mmol (1.65 g) of halogenated indigo derivative 3 to 100 mL of dichloromethane solvent. Add m-chloroperoxybenzoic acid (12 mmol, 2.07 g) in batches under ice bath conditions. Stir at room temperature for about 5 hours and monitor the reaction with TLC until it is complete. Filter, wash with saturated sodium bicarbonate, and oxidative rearrange to obtain a white solid halogenated indigo anhydride derivative 4.

[0040] (3) Preparation of halogenated tryptophan derivatives

[0041] Take a 150 mL round-bottom flask and add the halogenated indigo derivative 3 (10 mmol) and the halogenated indigo anhydride 4 (10 mmol, 1.65 g) prepared in the above steps to 100 mL of acetonitrile solvent, respectively. Using triethylamine as a catalyst, heat under reflux for 3 to 5 hours and monitor the reaction with TLC. After the reaction is completed, evaporate the solvent and separate by column chromatography to obtain the halogenated tryptophan ketone derivative 5.

[0042] (4) Preparation of the target compound 2,8-difluoro-3,9-bis(piperazin-1-yl)indol[2,1-b]quinazolin-6,12-dione

[0043] In a 50 mL round-bottom flask, 2,3,8,9-tetrafluoroindole[2,1-b]quinazoline-6,12-dione (1 mmol, 0.32 g) and piperazine (6 mmol, 0.52 g) were added separately. The mixture was heated and stirred at 90 °C for about 3 hours in N,N-dimethylformamide solvent (DMF, 35 mL). The reaction was monitored by TLC until complete. After cooling, 5.0 mL of methanol was added, and the mixture was allowed to stand for 30 min. The precipitated solid was filtered under vacuum, dried, and separated by column chromatography to obtain 2,8-difluoro-3,9-bis(piperazin-1-yl)indole[2,1-b]quinazoline-6,12-dione, with a yield of 50.9%.

[0044] Other similar fatty amine polysubstituted tryptophanone derivatives, based on halogenated tryptophanone derivatives, reacted with corresponding fatty amine compounds and other reagent raw materials, following the synthetic method of step (4) in Example. (5) Preparation of the target compound 9-((3-(dimethylamino)propyl)amino)-8-fluoro-3-(piperazin-1-yl)indolo[2,1-b]quinazolin-6,12-dione

[0045] In a 50 mL round-bottom flask, add 3,8,9-tetrafluoroindole[2,1-b]quinazoline-6,12-dione (1 mmol, 0.30 g) and N... 1 N 1 Dimethyl-1,3-propanediamine (3 mmol, 0.38 mL) was heated and stirred at 50 °C for about 2 hours in N,N-dimethylformamide solvent (DMF, 35 mL). Then, piperazine (3 mmol, 0.26 g) was added to the reaction system, the temperature was increased to 90 °C and stirred for about 3 hours, and the reaction was monitored by TLC until complete. After cooling, 5.0 mL of methanol was added, and the mixture was allowed to stand for 30 min. The precipitated solid was filtered under vacuum, dried, and separated by column chromatography to give 9-((3-(dimethylamino)propyl)amino)-8-fluoro-3-(piperazin-1-yl)indolo[2,1-b]quinazoline-6,12-dione, with a yield of 42.5%.

[0046] Other different fatty amine polysubstituted tryptamine derivatives, based on halogenated tryptamine derivatives, are first reacted with the corresponding primary amine fatty amine compound at 50°C, then reacted with the corresponding secondary amine fatty amine compound at 90°C, and with the action of other reagents and raw materials, following the synthesis method of step (5) in Example.

[0047] Chemical structural formulas and 1H NMR spectra of polysubstituted tryptophan derivatives of fatty amines ( 1 H NMR, carbon spectrum 13 The CNMR and high-resolution mass spectrometry (ESI-HRMS) data are shown in Table 1, and the physicochemical properties are shown in Table 2.

[0048] Table 1. Polysubstituted tryptophan derivatives of fatty amines 1 H NMR, 13 C NMR and ESI-HRMS data

[0049]

[0050]

[0051]

[0052]

[0053]

[0054]

[0055]

[0056]

[0057] Table 2 Physicochemical properties of fatty amine polysubstituted tryptophan derivatives

[0058]

[0059]

[0060] Example 2

[0061] Activity test against plant pathogens.

[0062] Test method:

[0063] (1) Prepare NA medium (1000mL). Weigh out beef extract (3.0g), peptone (5.0g), yeast powder (1.0g), glucose (10.0g), and agar (15.0g), dissolve them in 1000mL of ultrapure water, adjust the pH to about 7.2, and autoclave at 121℃ for 20 minutes before use.

[0064] (2) Prepare NB medium. Weigh out beef extract (3.0g), peptone (5.0g), yeast powder (1.0g), and glucose (10.0g), dissolve them in 1000mL of ultrapure water, adjust the pH to about 7.2, and autoclave at 121℃ for 20 minutes before use.

[0065] (3) Bacterial propagation. Select a single colony of pathogenic bacteria from NA solid culture medium and transfer it to NB liquid culture medium.

[0066] (4) Preparation of compound concentrations. The test concentrations of tryptophan derivatives and positive control drugs (e.g., tebuconazole and thiamethoxam) were 100 μg / mL and 50 μg / mL (DMSO as solvent).

[0067] (5) Turbidity test procedure. Add the target compound to 5 mL of NB liquid culture medium containing bacteria to prepare concentrations of 100 μg / mL and 50 μg / mL. Perform three parallel tests on three separate samples. Incubate on a constant-temperature shaker at 180 rpm and 28°C for 24 to 48 hours. After the blank control reaches the logarithmic growth phase, measure the OD of the liquid culture medium in all glass tubes at 595 nm. 595 value.

[0068] (6) Inhibition rate calculation. Before bacterial culture, the OD595 values ​​of all reagents and liquid culture medium blanks were measured to obtain the correction results. The inhibition rate calculation formula is as follows:

[0069] Correcting OD 595 = OD of bacterial culture medium 595 - Sterile culture medium OD 595 value

[0070]

[0071] Inhibition rate % = [(OD value of bacterial culture medium after correction - OD value of bacterial culture medium containing toxin after correction) / OD value of bacterial culture medium after correction] × 100.

[0072] The embodiments of this invention are provided to illustrate the technical solutions of this invention, but the content of the embodiments is not limited thereto. The plant pathogen bacteria inhibitory activity of the target compound is shown in Tables 3 and 4.

[0073] Table 3. Inhibitory activity of target compounds against plant pathogenic bacteria Xoo and Xoc.

[0074]

[0075]

[0076] BMT is the positive control drug tebuconazole, and TC is the positive control drug thiabendazole copper. The test result is the average of three measurements.

[0077] Table 4. Inhibitory activity of target compounds against plant pathogenic bacteria Xac and Psa.

[0078]

[0079]

[0080]

[0081] BMT is the positive control drug tebuconazole, and TC is the positive control drug thiabendazole copper. The test result is the average of three measurements.

[0082] The above experimental activity data indicate that the tested fatty amine polysubstituted tryptophan derivatives possess good inhibitory activity against plant pathogenic bacteria. At test concentrations of 100 μg / mL and 50 μg / mL, some compounds showed superior initial screening inhibitory activity compared to the positive control drugs tebuconazole and thiamethoxam. Specifically, compounds 3, 4, 22, 23, 28, 29, 30, and 33 showed greater inhibitory effects against Xoo and Xoc, while compounds 3, 9, 22, 29, 30, 33, 35, and 36 showed greater inhibitory effects against Xac and Psa than the positive control drugs tebuconazole and thiamethoxam. Compounds 16 and 17 selectively inhibited Xoc, compounds 6 and 7 selectively inhibited Xac, and compounds 16 and 39 also showed significant selective inhibition of Psa. Compounds 3, 22, 29, 30, and 33 exhibited strong broad-spectrum antibacterial effects against the four bacterial strains and can be considered as potential candidate drugs for inhibiting plant pathogenic bacteria, demonstrating good research value and application prospects.

[0083] Example 3

[0084] In vivo test of rice bacterial blight. Prepare a number of healthy rice plants grown in a greenhouse until they reach the tillering stage. Add an appropriate amount of the newly activated rice bacterial blight pathogen to NA medium and incubate at 28℃ and 180 rpm until the logarithmic growth stage.

[0085] (1) Preparation of compound concentration. Leaf blight (BT, 90%) and thiabendazole (TC, 20%) were used as positive control agents with a concentration of 200 μg / mL. An equal volume of DMSO solvent was used as a blank control. The concentration of test compound 3 was prepared to be 200 μg / mL.

[0086] (2) Bacterial culture medium. Xoo inoculation solution OD 595 The value is between 0.2 and 0.3.

[0087] (3) Leaf treatment. Cutting method: Cut off the leaf tip 1-2 cm away from the leaf tip of the rice leaf, and then spray and inoculate.

[0088] (4) Therapeutic activity. After the cut surface of rice was exposed to the bacterial solution, it was air-dried naturally. After 24 hours, it was treated with the agent by spraying. It was grown under the conditions of 28℃, 16 hours of light, 8 hours of darkness, and humidity greater than 95%. The disease was checked after 14 days.

[0089] (5) Protective activity. Rice leaves were sprayed with the protective agent and air-dried. After 24 hours, the cut surfaces of the rice plants were exposed to the bacterial solution and infected. The plants were then grown under conditions of 28°C, 16 hours of light, 8 hours of darkness, and humidity greater than 95%. The disease was checked after 14 days.

[0090] (6) Calculation of efficacy. To accurately calculate the in vivo activity, rice leaves were cut off, and the length of the whole leaf and the diseased leaf were accurately measured with a ruler. The proportion of disease infection was recorded, and the in vivo control effect of rice bacterial blight was calculated according to the disease index and control effect formula (Table 5).

[0091]

[0092] Table 5. In vivo control efficacy against rice bacterial leaf blight

[0093]

[0094] In vivo testing of rice bacterial blight pathogens showed that compound 3 exhibited good protective and therapeutic activity, superior to the positive control drug BMT. At a concentration of 200 μg / mL, it demonstrated significant protective and therapeutic effects against rice bacterial blight pathogens, potentially making it a small-molecule candidate drug with inhibitory activity against the pathogen.

[0095] The embodiments of this invention are provided to illustrate the technical solutions of this invention, but the content of the embodiments is not limited thereto.

Claims

1. A class of fatty amine polysubstituted tryptophanone derivatives, characterized in that: The compound has the structure shown in general formula (Ⅰ): Among them, X2, X4, Y2, and Y4 are hydrogen or halogens, and R1, R2, R3, and R4 are polysubstituted aliphatic amines.

2. The class of fatty amine polysubstituted tryptamine ketone derivatives according to claim 1, characterized in that: X2, X4, Y2, and Y4 are selected from mono- or poly-substituted or combined halogenated compounds of fluorine, chlorine, bromine, or iodine; R1, R2, R3, and R4 are di-, tri-, and tetra-substituted aliphatic amines or different aliphatic amine compounds, wherein the aliphatic amine compounds are selected from low-carbon aliphatic amines (C2-C8), higher aliphatic amines (C8-C22), amino acids, and piperazines.

3. The class of fatty amine polysubstituted tryptophanone derivatives according to claim 2, characterized in that: The fatty amine compounds are selected from morpholine, piperazine, 1-methylpiperazine, 2-methylpiperazine, ethylpiperazine, cyclopropylpiperazine, amide-piperazine derivatives, sulfonamide derivatives, piperazine heterocyclic substituted derivatives, piperidine derivatives, and N. 1 N 1 N 3 -Trimethyl-1,3-propanediamine, N 1 N 1 N 2 -Trimethylethane-1,2-diamine.

4. The method for preparing a class of fatty amine polysubstituted tryptamine ketone derivatives as described in any one of claims 1-3, characterized in that: Includes the following steps:

5. A type of composition, characterized in that: Contains the fatty amine polysubstituted tryptamine ketone derivatives according to any one of claims 1-3.

6. The use of the fatty amine polysubstituted tryptamine derivatives as described in any one of claims 1-3 or the composition as described in claim 5 in the preparation of drugs for treating agricultural pathogens and diseases.

7. The application according to claim 6, characterized in that: The pathogens and diseases mentioned are plant pathogenic bacteria diseases.

8. The application according to claim 7, characterized in that: The plant pathogens mentioned are rice bacterial blight pathogen, rice bacterial leaf streak pathogen, citrus canker pathogen, and kiwifruit canker pathogen.

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