Application of Flindersine derivative in prevention and treatment of agricultural fungal diseases

Abstract

The invention belongs to the field of natural medicinal chemistry, and discloses application of a series of Flindersine derivatives in prevention and treatment of agricultural fungal diseases. The derivatives show different degrees of inhibitory activity on two plant pathogenic fungi, wherein the Nb-2-2 has the best activity on rhizoctonia solani, the EC50 value of the Nb-2-2 can reach 6.228 mu g / mL, the Nb-2-2 has the best activity on magnaporthe oryzae, the EC50 value of the Nb-2-2 can reach 6.43 mu g / mL, the Nd-3 has the best activity on botrytis cinerea, the EC50 value of the Nd-3 can reach 2.956 mu g / mL, and the inhibitory activity is obviously superior to that of a control drug pyrimethanil. The synthesis method of the compound is simple, the raw materials are cheap and easy to obtain, and the compound is expected to be developed into a novel agricultural antibacterial agent. Structural formula of related compound as follows: # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the field of natural medicine chemistry, and discloses a new use of Flindersine alkaloid derivatives, specifically relating to the use of compounds S1 to Od-3 in preventing and treating agricultural fungal diseases caused by Rhizoctonia solani, Magnaporthe oryzae, and Botrytis cinerea. Background Art

[0002] Plant fungal diseases are one of the most difficult diseases to control during the growth of crops, causing large-scale damage to crops and huge economic losses. Due to the extensive and continuous use of chemical fungicides, the resistance of plant pathogenic fungi to fungicides has increased, seriously threatening human health and environmental safety. Therefore, the research and development of new pesticides with high efficiency, low toxicity, and low residue that can effectively control plant diseases have become one of the primary goals of current pesticide creation.

[0003] Pyranoquinolone alkaloids are widely distributed in nature. They have various biological activities and potential medicinal values, including antibacterial, anticancer, anti-inflammatory, and insecticidal effects. At the same time, they are also used as synthetic precursors for preparing other dimeric quinoline alkaloids and polyheterocycles. Among them, Flindersine is the parent compound in known pyranoquinoline natural products and is a 2-oxoquinolone compound. In recent years, important work has been carried out on synthesizing novel quinolone analogs with enhanced activities and potentially used for treating different fungal diseases. Due to these superior characteristics, high bioavailability, relatively low toxicity, and good pharmacokinetics have promoted the successful clinical trials of quinolone drugs.

[0004] Therefore, in the present invention, a series of Flindersine derivatives were designed and synthesized, and their antibacterial activities were evaluated. The test results showed that these compounds exhibited potential inhibitory effects against three types of agricultural fungi, namely Rhizoctonia solani, Magnaporthe oryzae, and Botrytis cinerea, which were significantly better than the control drug pyrimethanil, and are expected to be developed into a new type of agricultural drug against plant pathogenic fungi. Summary of the Invention

[0005] The present invention aims to reveal the new use of Flindersine derivatives in anti-plant pathogenic fungi, especially in the prevention and treatment of fungal diseases caused by Rhizoctonia solani, Magnaporthe oryzae, and Botrytis cinerea.

[0006] To achieve the above object, the present invention adopts the following technical method: The chemical structure of its compound is shown in Chemical Formula 1.

[0007]

[0008] The preparation method of the Flindersine derivatives S1 to Od-3 described in the present invention is shown in Chemical Formula 2:

[0009]

[0010] The Flindersine derivatives described in the present invention are compounds obtained according to the synthetic methods reported in the literature. Pure products are obtained by separation through conventional methods such as silica gel column chromatography. Through techniques such as nuclear magnetic resonance spectroscopy and mass spectrometry identification, the Flindersine derivatives described in the claims are determined. The results of activity screening show that the Flindersine derivatives described in the present invention exhibit good inhibitory effects against Rhizoctonia solani, Magnaporthe oryzae, and Botrytis cinerea.

[0011] The antibacterial compounds provided by the present invention have the following advantages:

[0012] 1) The present invention discovers that Flindersine derivatives exhibit excellent inhibitory effects against Rhizoctonia solani, Magnaporthe oryzae, and Botrytis cinerea, and have great application value in the treatment of phytopathogenic bacteria.

[0013] 2) Flindersine derivatives have the characteristics of easy synthesis, simple structure, and green and high efficiency, and have application value in the prevention and control of agricultural fungal pathogens, and are worthy of further research and development. Specific embodiments

[0014] To better understand the present invention, the above content of the present invention is further described in detail through the following specific embodiments. However, this should not be construed as a limitation of the present invention. The following are specific embodiments of the present invention, which further describe the technical solutions of the present invention. However, the content of the present invention is not limited to the scope described in the embodiments. Any change or equivalent substitution that does not deviate from the concept of the present invention is included in the protection scope of the present invention.

[0015] Example 1: Determination of the antibacterial activity of Flindersine derivatives against agricultural pathogenic bacteria and its results

[0016] 1) Test agents: Flindersine derivatives S1 to Od-3

[0017] 2) Test strains: Rhizoctonia solani, Magnaporthe oryzae, and Botrytis cinerea are provided by Gansu Academy of Agricultural Sciences.

[0018] 3) Antibacterial activity test:

[0019] Test method: The antibacterial activity was determined using potato dextrose agar medium (PDA medium). The preparation method is as follows: First, wash and peel the potatoes, weigh 200 g and cut them into small pieces, add water and boil until soft (boil for 20 - 30 minutes until the potato pieces can be pierced with a glass rod), filter with eight layers of gauze, heat, add 15 g of agar, continue heating and stirring until evenly mixed. After the agar is completely dissolved, add glucose and stir evenly. After slightly cooling, make up the volume to 1000 mL with water, dispense into conical flasks, stopper and wrap, sterilize at 115 °C for 2 h, and set aside. Dissolve the test agents in DMSO respectively, add them to the medium, mix evenly, so that the compound concentrations in the medium are 50 μg / mL respectively. Use DMSO at the same concentration as the blank control, and use the commercial drug azoxystrobin as the positive control. Pour the plates, inoculate after cooling, place them in an incubator at 23 °C for cultivation, and measure the inhibition rate of each compound with the blank control mycelium covering the culture dish as the limit. All tests were set up with three parallel groups or repeated three times. The inhibition rate was calculated according to the following formula:

[0020]

[0021] All experiments were set up with three replicates, and the inhibition rates of the compounds were measured and are shown in Table 1.

[0022] Table 1 Inhibition rates (%) of Flindersine derivatives against phytopathogenic fungi at 50 μg / mL

[0023]

[0024]

[0025] As can be seen from the test results in Table 1, the Flindersine derivatives involved in the present invention showed potential antibacterial activity against Rhizoctonia solani, Magnaporthe oryzae and Botrytis cinerea, and some of the compounds showed high activity.

[0026] Therefore, for the compounds with inhibition rates against Rhizoctonia solani, Magnaporthe oryzae and Botrytis cinerea greater than 70% at 50 μg / mL, further activity tests were carried out, and the EC 50 values (half-maximal effective concentration) were calculated using SPSS software, and the test data are shown in Table 2.

[0027] Table 2 EC 50 values (μg / mL) of Flindersine derivatives S1 - Od-3 against phytopathogenic fungi in vitro

[0028]

[0029]

[0030] Note: "-" indicates that the antibacterial activity of the compound was not determined

[0031] From the activity test results in Table 2, it can be seen that the Flindersine derivatives S1-Od-3 prepared in the present invention show different degrees of inhibitory activity against three plant pathogenic fungi. Among them, Nb-2-2 has the best activity against Rhizoctonia solani, and the EC 50 value can reach 6.228 μg / mL. Nb-2-2 has the best activity against Magnaporthe oryzae, and the EC 50 value can reach 6.43 μg / mL. Nd-3 has the best activity against Botrytis cinerea of tomato, and the EC 50 value can reach 2.956 μg / mL, which is significantly better than the control drug pyrimethanil. The raw materials of this type of derivative are easily available and easy to synthesize, and the antibacterial activity is significantly higher than that of the control drug pyrimethanil. This indicates that these compounds have the value of further development and are expected to be developed into new agricultural antifungal agents.

Claims

1. Use of a Flindersine derivative in preventing and controlling agricultural fungal diseases.

2. The use according to claim 1, wherein, The structural formula of the compound involved is as follows:

3. The new use of the Flindersine alkaloid derivative according to claims 1 and 2 in resisting phytopathogenic fungi, especially in preventing and controlling fungal diseases caused by Rhizoctonia solani, Magnaporthe oryzae and Botrytis cinerea.

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