Use of a class of medical nucleoside compounds in preventing and treating agricultural diseases

Abstract

The application belongs to the field of pharmaceutical chemistry, and discloses the use of nucleoside compounds in preventing and treating diseases caused by Sclerotinia sclerotiorum, Calonectria morganii, Botrytis cinerea, Gibberella zeae, Magnaporthe oryzae and Phytophthora capsici, wherein some of the compounds exhibit high inhibition and can be used for developing fungicidal lead compounds.

Description

Technical Field

[0001] This invention belongs to the field of medicinal chemistry and discloses a new use of a class of nucleoside compounds, specifically their use in the prevention and control of plant diseases caused by Sclerotinia sclerotiorum, Rhizoctonia solani, Botrytis cinerea, Fusarium graminearum, Fusarium graminearum, Rice blast fungus, and Phytophthora capsici. Background Technology

[0002] Agriculture is facing transformation and upgrading, with agricultural quality driven by green and brand-driven development. To safeguard food security and ecological safety, the requirements for pesticide research and development are also changing. Currently, while the incidence of common crop diseases in my country is decreasing, some special and new diseases are worsening, with some having alarmingly severe impacts. Therefore, this change provides new opportunities for the research, promotion, and application of fungicides. It is hoped that more and more new products and technologies will be applied to pest and disease control, contributing to agricultural transformation and upgrading and rural revitalization. Fungicides constitute a large portion of my country's annual pesticide imports, and the variety and quantity of fungicides in my country are relatively weak in the country's pesticide industry structure. There are over 700 types of crop diseases in my country, with over 300 being major crop diseases. In the past three years, the average annual affected area of ​​crop diseases in my country has been 1.715 billion mu (approximately 112 million hectares). In recent years, the overall incidence of major crop diseases in my country has been moderate to moderately severe.

[0003] Rice blast has entered another epidemic cycle. In 2016-2017, early rice blast was severe in Hunan and Jiangxi provinces in the middle and lower reaches of the Yangtze River, and locally severe in the Northeast rice-growing areas. The incidence of rice blast in my country is trending towards severity, and the disease has entered another epidemic cycle.

[0004] The development of pesticide resistance in wheat scab is rapid. In recent years, wheat scab in my country has been characterized by an expanding range of occurrence, increased frequency of severe outbreaks, greater severity, and increased damage and losses, with the pathogen exhibiting rapid resistance development. In the past six years, 2010, 2012, and 2016 saw severe and large-scale outbreaks, with the incidence reaching 50%, particularly in the wheat-growing areas of the middle and lower reaches of the Yangtze River, where the frequency of large-scale outbreaks was high and the damage and losses were significant. In recent years, scab in the Huang-Huai winter wheat region of my country has shown a trend of increasing severity year by year, exhibiting a northward and westward expansion, and has become a common disease in the Huang-Huai wheat region. Therefore, the development of active ingredients in biopesticides will receive more attention, and the market prospects are broad.

[0005] Nucleosides play a crucial role in gene replication and transcription, and nucleoside compounds possess a variety of biological activities, such as antitumor, antibacterial, and antiviral activity. Therefore, they have been used in chemotherapy, antibacterial, and antiviral therapies for decades. Nucleoside analogs have one or more modifications, thus mimicking the structure of natural nucleosides, making them suitable for inclusion in the DNA or RNA replication cycle. Inclusion of nucleoside analogs in DNA or RNA may terminate strand elongation or lead to the accumulation of mutations. Therefore, further evaluation of the antibacterial activity of nucleoside compounds provides a new pathway to solving the globally recognized challenge of developing innovative pesticides. Summary of the Invention

[0006] The purpose of this invention is to address the deficiencies in existing technologies by providing superior fungicides for agricultural production, and to explore the use of nucleoside compounds in the prevention and control of agricultural diseases.

[0007] To achieve the above objectives, the present invention provides the following technical method: a class of nucleoside compounds for preventing and controlling diseases caused by Sclerotinia sclerotiorum, Rhizoctonia solani, Botrytis cinerea, Fusarium graminearum, Rice blast fungus, and Phytophthora capsici, namely compounds 1 to 9, the structural formulas of which are shown in 1 to 9.

[0008] Detailed Implementation

[0009] To better understand the present invention, the following detailed description of specific embodiments further illustrates the above-mentioned aspects of the present invention. However, this should not be construed as a limitation of the present invention.

[0010] Example 1: Compounds 1-9 are as follows.

[0011] 5-Fluorouracil nucleoside (1) CAS: 316-46-1, purity >98%; 5'-deoxy-5-fluorouridine (2) CAS: 3094-09-5, purity >98%; uridine (3) CAS: 58-96-8, purity >98%; uridine (4) CAS: 3083-77-0, purity >98%; 5-trifluoromethyluracil (5) CAS: 54-20- 6. Purity > 97%; 5-bromo-2'-deoxyuridine (bromoureidine) (6) CAS: 59-14-3, purity > 98%; 2'-deoxyguanosine (7) CAS: 961-07-9, purity > 98%; Ganciclovir (8) CAS: 82410-32-0, purity > 98%; 5-fluoro-2'-deoxyuridine (9) CAS: 50-91-9, purity > 98%.

[0012] Example 2: Indoor antifungal activity assay and results

[0013] The plant pathogenic fungi used in this experiment were laboratory-preserved strains, and the culture medium used was potato agar-dextrose medium (PDA).

[0014] PDA medium formula: 200g potato (peeled), 20g glucose, 15g agar, 1000mL distilled water, natural pH.

[0015] PDA culture medium preparation method: Wash and peel potatoes, weigh 200g and cut into small pieces, boil in distilled water for about 20 minutes, filter with eight layers of gauze, add distilled water to make up to 1000mL, add 15g agar and 20g glucose, stir to dissolve fully, dispense into Erlenmeyer flasks, sterilize at 121℃ for 20 minutes, cool and use for later use.

[0016] Experimental methods

[0017] 1) The mycelial growth rate method was used.

[0018] 1. Activation of bacterial strains: Incubate plant pathogens on PDA plates at 25°C for 3–6 days.

[0019] 2. Preparation of drug plates: Heat and melt the PDA culture medium, cool it to 45-50℃, and add different concentrations of nucleoside compounds to make drug-loaded plates.

[0020] 3. Inoculation and cultivation: In a clean bench, use a punch to make a 5mm diameter mycelium cake at the edge of the mycelium after 3-6 days of cultivation (with the growth conditions as uniform as possible), then inoculate it into the center of the plate with an inoculation needle, and then incubate it upside down in an incubator (25℃).

[0021] 4. Results determination: After the hyphae in the blank control group were fully grown, the growth diameter of the hyphae in the drug-treated group was measured using the cross-cross method, and the inhibition rate was calculated.

[0022] 5. Inhibition rate (%) = (Control mycelial diameter - Treated mycelial diameter) / (Control mycelial diameter - Mycelial cake diameter) × 100

[0023] 6. Set up 3 parallel experiments for each concentration.

[0024] Table 1. Antibacterial activity of nucleoside compounds against plant pathogenic fungi.

[0025]

[0026]

[0027] Note: Each treatment was repeated three times in the experiment, and the data in the table is the average of the three repetitions.

[0028] As shown in Table 1, the nucleoside compounds involved in this invention exhibit good inhibitory activity against *Sclerotinia sclerotinia*, *Rhizoctonia solani*, *Botrytis cinerea*, *Fusarium graminearum*, and *Phytophthora capsici*. Compounds 1 and 9, in particular, demonstrate excellent antibacterial activity against *Sclerotinia sclerotinia* and *Botrytis cinerea*. In conclusion, the nucleoside compounds described in this invention possess simple structures and exhibit good inhibitory activity against agricultural pathogens, making them worthy of further research and development.

Claims

1. The use of a nucleoside compound in the prevention and control of agricultural diseases, wherein the structural formula of the nucleoside compound is as follows: ， Its features are, The use of the nucleoside compounds in the prevention and control of diseases caused by Rhizoctonia solani, Sclerotinia sclerotiorum var. spp., Botrytis cinerea, Fusarium graminearum, Rice blast fungus, and Phytophthora capsici.

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