Novel macrolide compound as well as preparation method and application thereof

Abstract

The invention discloses a novel macrolide compound as well as a preparation method and application thereof. The structural formula of the compound is shown as a formula I. The compound is separated from an Alternaria sp. XZ146 solid fermentation extract for the first time, and meanwhile, the antibacterial activity of the compound is reported for the first time. The compound can be used for preparing a bacteriostatic agent, especially a vibrio bacteriostatic agent.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of natural medicine, and particularly relates to a macrolide compound isolated from a rice fermentation product of Alternaria alternata (Fr. Alternaria sp.) and a preparation method and use thereof. BACKGROUND

[0002] The health threat caused by bacteria is in a serious situation both globally and in China. According to the latest report of the World Health Organization, about 1.27 million people die directly from drug-resistant bacterial infections every year. The data of the National Health Commission of China in 2024 shows that the incidence of drug-resistant bacterial infection in hospitals increased by 5.3% compared with the previous year, and the detection rate of carbapenem-resistant Klebsiella pneumoniae (CRKP) reached as high as 28.7%. In terms of foodborne diseases, more than 10,000 cases of bacterial food poisoning are reported annually nationwide, and Salmonella and Vibrio parahaemolyticus are the main pathogens, among which the microbial contamination rate of retail fresh food is still as high as 12.8%. In addition, Mycobacterium tuberculosis causes about 64,000 new cases in China every year, and the prevention and control of drug-resistant tuberculosis is facing continuous challenges. These data highlight the major challenges faced by the public health system under the dual pressure of the spread of bacterial drug resistance and foodborne diseases.

[0003] Fungi can produce a series of macrolide compounds, which have rich structural types and diverse biological activities. This class of natural products is a class of 12-16 carbon lactone ring structures, widely distributed in actinomycetes and fungi, and is an important source of drugs. Important macrolide compounds include antibacterial drugs erythromycin and immunosuppressant rapamycin. The present application relates to a new macrolide compound isolated and prepared from rice fermentation product of Alternaria alternata and its antibacterial use, which has not been reported so far. SUMMARY

[0004] The purpose of the present application is to provide a natural macrolide compound, a preparation method thereof, and use thereof in preparing antibacterial drugs.

[0005] In order to achieve the above-mentioned purpose, the technical scheme adopted by the present application is as follows: The first aspect of the present application provides a compound represented by formula I or a pharmaceutically acceptable salt thereof:

[0006] The second aspect of the present application provides a strain of Alternaria alternata (Fr. Alternaria sp.) XZ146.

[0007] The Alternaria alternata (Fr. AlternariaXZ146, isolated from a soil sample on the Tibetan Plateau, has been deposited with the China General Microbiological Culture Collection Center (CGMCC, located at No. 1, Yikhina West Road, Yard 3, Beijing Chaoyang District, Institute of Microbiology of Chinese Academy of Sciences, Beijing 100101, China) on October 10, 2025, and has been given the accession number CGMCC No. 42239, and has been named Alternaria alternata Alternaria XZ146.

[0008] The third aspect of the present application provides a fermentation broth or extract of the strain.

[0009] The fermentation broth or extract of the strain provided by the present application is a fermentation broth or extract of Alternaria alternata (Alternaria alternata) Alternaria XZ146.

[0010] Further, the fermentation broth or extract contains a compound represented by Formula I.

[0011] The fourth aspect of the present application provides the use of the strain of the second aspect of the present application in the preparation of a compound represented by Formula I or a pharmaceutically acceptable salt thereof.

[0012] The fifth aspect of the present application provides a preparation method of the compound represented by Formula I.

[0013] The preparation method of the compound represented by Formula I provided by the present application comprises fermenting the strain of the second aspect of the present application to obtain the compound represented by Formula I.

[0014] Specifically, the preparation method of the compound represented by Formula I comprises the following steps: a) solid-state fermentation of Alternaria alternata (Alternaria alternata) Alternaria XZ146 to obtain a fermentation culture; b) extracting the fermentation culture obtained in step a) with a suitable organic solvent for a suitable number of times, combining the extract, and obtaining a crude extract after separating the organic solvent from the extract; c) chromatographically separating the crude extract obtained in step b) to obtain an active component solution, and separating the active component solution by high performance liquid chromatography to obtain the compound represented by Formula I.

[0015] In the above preparation method, in step a), the fermentation uses a rice culture medium; the rice culture medium can be prepared by mixing rice and water in a ratio of 1.6 Kg: 2400 mL.

[0016] In the above preparation method, in step a), the fermentation temperature is 20-30°C, preferably 22-28°C, and more preferably 25°C. In the above preparation method, in step a), the fermentation time is 25 to 35 days, preferably 28 to 32 days, and more preferably 30 days.

[0017] In the above preparation method, step b) describes an extraction method of soaking extraction.

[0018] Furthermore, the soaking time is at least 12 hours, preferably 0.5 to 2 days, and more preferably 1 day.

[0019] In the above preparation method, in step b), the extraction is performed 1 to 5 times, preferably 2 to 4 times, and more preferably 3 times.

[0020] In the above preparation method, in step b), the organic solvent is methanol, acetone or ethyl acetate, preferably acetone or ethyl acetate, and more preferably ethyl acetate.

[0021] In the above preparation method, step b) involves separating the organic solvent by distillation, and more preferably by vacuum distillation.

[0022] In the above preparation method, step c) involves chromatographic separation, which is silica gel column chromatography and / or gel chromatography; further, the silica gel column chromatography is preferably vacuum silica gel column chromatography.

[0023] Preferably, the crude extract obtained in step b) is subjected to silica gel column chromatography and gel chromatography for separation in sequence; Further, in the silica gel column chromatography separation step, the mobile phase is a mixture of petroleum ether, dichloromethane, and ethyl acetate; elution is performed according to the following elution program: gradient elution is performed sequentially using 11 different mobile phases, in the following order: petroleum ether:dichloromethane (v / v) = 100:0, 80:20, 60:40, 40:60, 20:80, 10:90, 0:100; dichloromethane:ethyl acetate (v / v) = 90:10, 80:20, 70:30, 60:40. Each gradient is eluted by 2-3 column volumes, and the eluent obtained by eluting with a dichloromethane to ethyl acetate volume ratio of 60:40 is the active component solution.

[0024] Furthermore, in the gel chromatography separation step, the mobile phase is a mixed solvent of chloroform and methanol in a volume ratio of 1:1.

[0025] According to an embodiment of the present invention, the active component solution was separated by gel chromatography. The gel chromatography column was 60cm × 2.5cm (purchased from Newwell Glass Instruments Co., Ltd.), and the gel packing material was Sephadex LH-20 dextran gel (purchased from GE Healthcare Bio-Sciences AB). 60g of gel was packed into the column, and the mobile phase was a 1:1 mixture of chloroform and methanol. The gels were collected in the order of elution, with each 5mL representing one subfraction, for a total of 15 subfractions. Then, under the guidance of activity tracking [testing the minimum inhibitory concentration (MIC) of the 15 components against Vibrio harveyi and Vibrio alginolyticus, the specific test method is as described in Example 3, and an MIC less than or equal to 64μg / mL is considered to have inhibitory activity], the 10th subfraction (named subfractions 1-10) was found to have inhibitory activity.

[0026] In the above preparation method, in step c), the mobile phase in the high-performance liquid chromatography separation step is a methanol-water solution; preferably, the volume ratio of methanol to water is 65:35.

[0027] Preferably, the high-performance liquid chromatography separation conditions are as follows: using a C18 reversed-phase column, and using a mixture of methanol and water with a volume ratio of 65:35 as the mobile phase for isocratic elution.

[0028] In one embodiment of the present invention, the chromatograph used is specifically an Agilent 1260 semi-preparative high-performance liquid chromatograph. The C18 reversed-phase column is specifically an Agilent C18 reversed-phase semi-preparative column (5 μm; 9.4 × 250 mm). The elution flow rate for isocratic elution is 3.0 mL / min, and the elution time is 40 min.

[0029] Under the above conditions, the compound was separated and purified by high performance liquid chromatography, and the elution peak with a retention time of 30.5 min was collected to obtain the compound shown in Formula I.

[0030] A sixth aspect of the present invention provides a pharmaceutical composition.

[0031] The pharmaceutical composition comprises a compound of Formula I provided in the first aspect of the invention or a pharmaceutically acceptable salt thereof.

[0032] Furthermore, the pharmaceutical composition may also include an optional pharmaceutically acceptable carrier.

[0033] The pharmaceutical composition described above can be formulated into various forms such as injections, tablets, powders, granules, capsules, oral liquids, ointments, and creams. All of these dosage forms can be prepared using conventional methods in the pharmaceutical field. The carrier includes conventional pharmaceutical components such as diluents, excipients, fillers, binders, wetting agents, disintegrants, absorption enhancers, surfactants, adsorbents, and lubricants.

[0034] The pharmaceutical composition can be introduced into the body, such as into muscles, intradermal tissues, subcutaneous tissues, veins, or mucous membranes, by means of injection, spray, nasal drops, eye drops, penetration, absorption, or physical or chemical mediation; or it can be introduced into the body after being mixed or encapsulated with other substances.

[0035] The seventh aspect of the present invention provides the use of the compound of formula I as described in the first aspect of the present invention or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition described in the sixth aspect of the present invention, in at least one of the following aspects: 1) Application in the preparation of bacterial inhibitors; 2) Use in the preparation of products for the prevention and / or treatment of bacterial infections; 3) Use in the preparation of products for the prevention and / or treatment of diseases caused by bacterial infections; 4) Application in inhibiting bacterial growth in vitro; 5) Application in the preparation of biocontrol agents for the prevention and control of aquatic diseases; 6) Application in the preparation of feed for the prevention and control of aquatic diseases.

[0036] Furthermore, the bacteria are aquatic bacteria; even further, the aquatic bacteria are Vibrio, and the Vibrio is at least one of the following: Vibrio harveyi and Vibrio alginolyticus.

[0037] Furthermore, the product that inhibits bacterial growth is an aquatic bacteria inhibitor, and even more specifically, a Vibrio inhibitor.

[0038] Furthermore, the aquatic diseases are caused by Vibrio bacteria. The Vibrio bacteria are at least one of the following: Vibrio harveyi and Vibrio alginolyticus.

[0039] The eighth aspect of the present invention provides a product.

[0040] The product comprises a compound of Formula I as described in the first aspect of the present invention or a pharmaceutically acceptable salt thereof. It has at least one of the following effects: a) Inhibits bacterial growth; b) Prevention and / or treatment of bacterial infections; c) Prevention and / or treatment of diseases caused by bacterial infections; d) Prevention and control of aquatic diseases.

[0041] The product is a pharmaceutical, inhibitor, biocontrol agent, or feed.

[0042] The compound represented by Formula I provided by this invention is a novel compound that was first isolated and named from microbial solid fermentation extracts, and its antibacterial activity was also reported for the first time.

[0043] Instructions for the Preservation of Biological Materials Classification and nomenclature of biological materials: Alternaria Alternaria sp. Strain number of the biological material: XZ146 Full name of the depository: China General Microbiological Culture Collection Center, China Microbiological Culture Collection Committee Abbreviation of depositary institution: CGMCC Address: No. 3, Courtyard 1, Beichen West Road, Chaoyang District, Beijing Deposit date: October 10, 2025 Accession number: CGMCC No. 42239. Attached Figure Description

[0044] Figure 1 Nuclear magnetic resonance of the compound shown in Formula I 1 H-NMR spectrum; Figure 2 Nuclear magnetic resonance of the compound shown in Formula I 13 C-NMR spectrum; Figure 3 The HSQC nuclear magnetic resonance spectrum of the compound shown in Formula I is shown below. Figure 4 The nuclear magnetic resonance HMBC spectrum of the compound shown in Formula I is shown below. Figure 5 The measured CD spectrum and calculated ECD spectrum of the compound shown in Formula I are shown. Detailed Implementation

[0045] The embodiments of the present invention will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of the invention. Unless otherwise specified in the examples, conventional conditions or conditions recommended by the manufacturer are followed. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0046] In the quantitative experiments described below, three replicate experiments were conducted, and the average value of the results was taken.

[0047] Example 1, Alternaria (Alternaria Isolation, Identification and Preservation of sp.) XZ146 Alternaria ( Alternaria (sp.) Separation of XZ146 Low-temperature fungi isolated from soil samples from the Tibetan Plateau in June 2009.

[0048] Alternaria ( Alternaria Identification of sp.) XZ146 Morphological characteristics: Rapidly growing, initially dark white, later turning grayish-brown to dark olive, with the back mostly brown or blackish-brown, commonly showing 3-4 pairs of concentric rings; hyphae brownish-green, with transverse septa; conidiophores erect or slightly curved, solitary or a few clustered, 18-65 µm long, 3-7 µm wide; conidia obclavate, obpipiceate, or elliptical, often with a short columnar beak at the apex, 30-42 µm × 6-20 µm in size. They have 3-7 transverse septa and 0-4 longitudinal septa, exhibiting a typical "brick-like" or "wall-brick-like" structure. The ITS gene sequence is shown in sequence 1 of the sequence listing (SEQ ID No. 1). Based on ITS phylogenetic analysis and morphological identification, strain XZ146 belongs to *Alternaria* (*Alternaria*). Alternaria sp.).

[0049] Alternaria ( Alternaria (sp.)XZ146 Preservation Alternaria ( Alternaria Alternaria sp.) XZ146 was deposited on October 10, 2025, at the China General Microbiological Culture Collection Center (CGMCC, address: No. 3, Courtyard 1, Beichen West Road, Chaoyang District, Beijing, Institute of Microbiology, Chinese Academy of Sciences, 100101, China), with accession number CGMCC No. 42239, and classified as Alternaria sp. Alternaria (sp.), strain name XZ146.

[0050] Example 2: Preparation of the compound shown in Formula I a. Solid-state fermentation of strain XZ146 Activation of strain XZ146. PDA medium: 200g potato, 20g glucose, 15g agar, 1000mL purified water, autoclaved at 121℃ for 30 minutes, prepared into test tube slants, mycelium picked and inoculated onto the test tube slants, cultured at 25℃ for 10 days.

[0051] Solid-state fermentation of strain XZ146. Preparation of rice culture medium (1.6 kg of rice and 2400 mL of purified water were added equally to 20 500 mL Erlenmeyer flasks, soaked overnight, autoclaved at 121°C for 30 minutes, and cooled before use); mycelium was picked from test tube slant and placed in test tubes containing sterile water to prepare a bacterial suspension; the prepared bacterial suspension (spore concentration 1 × 10⁻⁶) was then used... 6 5 mL of the culture medium (each cell / mL) was inoculated onto rice culture medium and fermented in a sterile culture room at 25°C for 40 days to obtain the fermented culture.

[0052] b. Extraction of crude extract The fermentation culture obtained in step a was crushed with a glass rod (0.8cm × 30cm), and 4.0L of ethyl acetate was added. In 20 Erlenmeyer flasks (200 mL each), the mixture was left to stand for 1 day. The mixture was then filtered at room temperature and atmospheric pressure using medium-speed qualitative filter paper (12.5 cm in diameter, purchased from Hangzhou Special Paper Co., Ltd.) to obtain the organic phase and residue. The organic phase was designated as crude extract I, and the residue was designated as residue I. Add 4.0 L of ethyl acetate to Residue I (20 bottles in total, 200 mL per bottle), let stand and soak for 1 day, filter to obtain organic phase and residue, and label the organic phase as crude extract II and the residue as residue II. Add 4.0 L of ethyl acetate to residue II (20 bottles in total, 200 mL per bottle), let stand and soak for 1 day, filter to obtain organic phase and residue, and label the organic phase as crude extract III and the residue as residue III. Combine crude extract I, crude extract II, and crude extract III, and denote them as crude extract.

[0053] The crude extract was distilled under reduced pressure until dry to obtain 10.5 g of crude extract.

[0054] c. Separation and purification of crude extract The crude extract was packed into a vacuum chromatography silica gel column [vacuum chromatography silica gel column (40cm × 8.5cm), purchased from Beijing Glass Instruments Co., Ltd.; the silica gel used was thin-layer chromatography silica gel H, purchased from Qingdao Ocean Chemical Co., Ltd. 120g silica gel was packed in the column]. Vacuum chromatography was performed using a petroleum ether-dichloromethane-ethyl acetate-methanol system. The mobile phases used were: petroleum ether:dichloromethane (v / v) = 100:0, 80:20, 60:40, 40:60, 20:80, 10:90, 0:100; dichloromethane:ethyl acetate (v / v) = 90:10, 80:20, 70:30, 60:40, 50:50, 4... 0:60, 30:70, 20:80, 10:90, 0:100; ethyl acetate:methanol (v / v) = 98:2, 95:5, 90:10, 0:100; a total of 21 gradients, each with an elution volume of 400 mL. The eluent of each gradient was distilled under reduced pressure, and the crude extract was separated into 21 fractions in order of increasing polarity. Under the guidance of activity tracking [testing the MIC values ​​of the 21 fractions against Vibrio harveyi and Vibrio alginolyticus, the specific test method is as described in Example 4, and an MIC less than or equal to 64 μg / mL is considered to have inhibitory activity], it was found that the fraction obtained by elution with dichloromethane:ethyl acetate = 60:40 (v / v) as the mobile phase (named fraction 1) had inhibitory activity, and active fraction 1 (135 mg) was collected.

[0055] Active component 1 was separated by gel chromatography using a 60cm × 2.5cm column (purchased from Newwell Glass Instruments). The gel packing material used was Sephadex LH-20 dextran gel (purchased from GE Healthcare BioSciences AB), with 60g of gel packed in the column. The mobile phase was a chloroform to methanol solution with a volume ratio of 1:1. Subfractions were collected in the order of elution, with each 5mL representing one subfraction, for a total of 15 subfractions. Then, under the guidance of activity tracking [testing the MIC values ​​of the 15 components against Vibrio harveyi and Vibrio alginolyticus, with the specific test method as described in Example 3, where an MIC less than or equal to 64 μg / mL was considered inhibitory activity], the 10th subfraction (named subfraction 1-10) was found to have inhibitory activity, and active subfraction 1-10 (43mg) was collected. The active subfractions 1-10 were purified by HPLC to obtain 2.5 mg of the compound represented by Formula I. The HPLC conditions were as follows: an Agilent 1260 semi-preparative high-performance liquid chromatograph was used, with an Agilent C18 reversed-phase semi-preparative column (5 μm, 9.4 × 250 mm), a flow rate of 3.0 mL / min, and methanol and water as the mobile phase. The preparation conditions were: isocratic elution with methanol / water (65 / 35, v / v) for 40 min to obtain the compound represented by Formula I. The retention time t R = 30.5 minutes.

[0056] In summary, 10.5 g of crude extract was purified to yield 2.5 mg of the compound shown in Formula I, with a yield of 0.02%.

[0057] Example 3: Structural characterization of the compound shown in Formula I The compound of Formula I prepared in Example 1 was analyzed by high-resolution mass spectrometry (HRESIMS), infrared spectroscopy (IR), ultraviolet spectroscopy (UV), nuclear magnetic resonance spectroscopy (NMR), circular dichroism spectroscopy (CD), and rotational spectroscopy (ORD). The high-resolution mass spectrometry was provided by the Institute of Materia Medica, Chinese Academy of Medical Sciences (Agilent Accurate-Mass-Q-TOF LC / MSG6550 instrument), the nuclear magnetic resonance spectroscopy (Bruker Avance III-600 instrument) and circular dichroism spectroscopy (JASCO J-815 instrument) were provided by the National Center for Drug and Metabolite Analysis, Institute of Materia Medica, Chinese Academy of Medical Sciences, and the infrared spectroscopy (Nicolet Magna-IR 750 instrument), ultraviolet spectroscopy (Shimadzu Biospec-1601 instrument), and rotational spectroscopy (Autopol IV instrument) were provided by the Institute of Microbiology, Chinese Academy of Sciences.

[0058] Based on the above tests and analyses, the physicochemical data of the compound of formula I prepared in Example 1 are as follows: white powder; molecular formula: C 22 H 23 O6; Molecular weight: 382; High-resolution mass spectrometry (HRESIMS): m / z 383.1483 [M+H] + (Calculated C) 22 H 23 O6, 383.1489); 1H NMR spectrum ( 1 H-NMR and carbon spectroscopy (H-NMR) 13 C-NMR data are shown in Table 1: Table 1. Proton NMR spectra of the compounds shown in Formula I ( 1 H-NMR and carbon spectroscopy (H-NMR) 13 C-NMR data

[0059] a at 600MHz with Acetone- d 6 represents solvent testing.

[0060] b at 150MHz with Acetone- d 6 represents solvent testing.

[0061] The proton nuclear magnetic resonance spectrum of the compound shown in Formula I above ( Figure 1 ), carbon spectrum ( Figure 2 ) and mass spectrometry, combined with the two-dimensional nuclear magnetic resonance spectrum (HSQC) of this compound. Figure 3 ) and HMBC ( Figure 4 ) spectrum, and measured CD and calculated ECD spectra ( Figure 5 The chemical formula of the confirmed compound is shown in Formula I:

[0062] In summary, from Alternaria ( Alternaria The compound represented by formula I was extracted and isolated from sp. XZ146. After further purification, the structural characteristics of the compound were identified by high-resolution mass spectrometry, nuclear magnetic resonance technology and circular dichroism data analysis.

[0063] Example 4: Detection of antibacterial activity of the compound shown in Formula I The MIC values ​​against bacteria were determined using the broth microdilution antibacterial assay (M07-A8) from the Clinical Laboratory Standards Institute (CLSI). The test samples were the compound of Formula I prepared in Example 2 and the positive control chloramphenicol. The detection medium was calcium-modified MH broth. The final concentrations of the compound of Formula I were diluted to 512 μg / mL, 256 μg / mL, 128 μg / mL, 64 μg / mL, 32 μg / mL, 16 μg / mL, 8 μg / mL, and 4 μg / mL using calcium-modified MH broth; the final concentrations of chloramphenicol were diluted to 64 μg / mL, 32 μg / mL, 16 μg / mL, 8 μg / mL, 4 μg / mL, 2 μg / mL, 1 μg / mL, and 0.5 μg / mL.

[0064] The results are shown in Table 2.

[0065] The Vibrio alginolyticus used in the table below is Vibrio alginolyticus ATCC33787, purchased from AlgaeBio; the Vibrio harveyi is Vibrio harveyi ATCC 33842, purchased from AlgaeBio.

[0066] Table 2. Antibacterial MIC values ​​(μg / mL)

[0067] The present invention has been described in detail above. For those skilled in the art, the invention can be practiced in a wide range of ways with equivalent parameters, concentrations, and conditions without departing from its spirit and scope, and without requiring unnecessary experiments. Although specific embodiments have been given, it should be understood that further modifications can be made to the invention. In summary, according to the principles of the invention, this application is intended to include any changes, uses, or improvements to the invention, including changes made using conventional techniques known in the art that depart from the scope disclosed herein. Some of the essential features can be applied within the scope of the following appended claims.

Claims

1. The compound represented by Formula I or a pharmaceutically acceptable salt thereof: 。 2. Alternaria ( Alternaria sp.)XZ146, with accession number CGMCC No. 42239.

3. The Alternaria alternata according to claim 2 ( Alternaria The use of sp.) XZ146 in the preparation of the compound of claim 1 or a pharmaceutically acceptable salt thereof.

4. A method for preparing the compound of claim 1, comprising: Fermentation of Alternaria as described in claim 2 ( Alternaria sp.)XZ146, to obtain the compound of claim 1.

5. The preparation method according to claim 4, characterized in that: The method includes the following steps: a) Alternaria ( Alternaria Solid-state fermentation was performed on sp.)XZ146 to obtain a fermentation culture; b) Extract the fermentation culture obtained in step a) with an organic solvent, collect the extract, and separate the organic solvent to obtain the crude extract; c) The crude extract obtained in step b) is subjected to chromatographic separation to obtain an active component solution. The active component solution is then separated by high performance liquid chromatography to obtain the compound shown in Formula I.

6. The preparation method according to claim 5, characterized in that: In step a), the culture medium used for fermentation is rice culture medium; And / or, in step a), the fermentation temperature is 20–30°C; And / or, in step a), the fermentation time is 25 to 35 days; And / or, in step b), the extraction method is soaking extraction; further, the soaking time is at least 12 hours; And / or, in step b), the extraction is performed 1 to 5 times; And / or, in step b), the organic solvent is methanol, acetone, or ethyl acetate; And / or, in step b), the method of separating the organic solvent is distillation.

7. The preparation method according to claim 5 or 6, characterized in that: In step c), the chromatographic separation is silica gel column chromatography and / or gel chromatography; preferably, the crude extract obtained in step b) is subjected to silica gel column chromatography and gel chromatography in sequence. Further, in the silica gel column chromatography separation step, the mobile phase is a mixture of petroleum ether, dichloromethane, and ethyl acetate; elution is performed according to the following elution program: gradient elution is performed sequentially using 11 different mobile phases, in the following order: petroleum ether:dichloromethane (v / v) = 100:0, 80:20, 60:40, 40:60, 20:80, 10:90, 0:100; dichloromethane:ethyl acetate (v / v) = 90:10, 80:20, 70:30, 60:

40. Each gradient is eluted by 2-3 column volumes, and the eluent obtained by eluting with a dichloromethane to ethyl acetate volume ratio of 60:40 is collected as the mobile phase, which is the active component solution; Furthermore, in the gel chromatography separation step, the mobile phase is a mixed solvent of chloroform and methanol in a volume ratio of 1:1; And / or, in step c), the mobile phase in the high performance liquid chromatography separation step is a methanol-water solution; Furthermore, the conditions for high-performance liquid chromatography separation are as follows: using a C18 reversed-phase column, and using a mixture of methanol and water with a volume ratio of 65:35 as the mobile phase for isocratic elution.

8. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof, and optionally one or more pharmaceutically acceptable excipients.

9. The use of the compound of claim 1 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 8, in any of the following 1)-6): 1) Application in the preparation of bacterial inhibitors; 2) Use in the preparation of products for the prevention and / or treatment of bacterial infections; 3) Use in the preparation of products for the prevention and / or treatment of diseases caused by bacterial infections; 4) Application in inhibiting bacterial growth in vitro; 5) Application in the preparation of biocontrol agents for the prevention and control of aquatic diseases; 6) Application in the preparation of feed for the prevention and control of aquatic diseases; Furthermore, the bacteria are aquatic bacteria. More specifically, the aquatic bacteria are Vibrio, and the Vibrio is at least one of the following: Vibrio harveyi and Vibrio alginolyticus. Furthermore, the product that inhibits bacterial growth is an aquatic bacteria inhibitor, and even further, the aquatic bacteria inhibitor is a Vibrio inhibitor; Furthermore, the aquatic disease is an aquatic disease caused by Vibrio; even further, the Vibrio is at least one of the following: Vibrio harveyi and Vibrio alginolyticus.

10. A product comprising the compound of formula I as claimed in claim 1 or a pharmaceutically acceptable salt thereof; The product has at least one of the following effects: a) Inhibits bacterial growth; b) Prevention and / or treatment of bacterial infections; c) Prevention and / or treatment of diseases caused by bacterial infections; d) Prevention and control of aquatic diseases; The product is a pharmaceutical, inhibitor, biocontrol agent, or feed. Furthermore, the bacteria are aquatic bacteria; even further, the aquatic bacteria are Vibrio, and the Vibrio is at least one of the following: Vibrio harveyi and Vibrio alginolyticus. Furthermore, the aquatic disease is an aquatic disease caused by Vibrio; even further, the Vibrio is at least one of the following: Vibrio harveyi and Vibrio alginolyticus.

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