Application of closantel compound in inhibiting growth of blue-green algae

Abstract

The invention provides application of closantel compounds in inhibition of growth of blue-green algae, and relates to the technical fields of environmental protection, aquaculture and the like. The cyanobacteria fructose 1, 6-diphosphate / sedoheptulose-1, 7-diphosphatase enzyme body experiment shows that the closantel compound has a relatively good inhibition effect on cyanobacteria Cy-FBP / SBPase, and the IC50 of the closantel compound is 0.16 + / -0.01 [mu] M to 15.3 + / -1.7 [mu] M. The cyanobacteria growth inhibition experiment shows that the EC50 for inhibiting various cyanobacteria is 0.46-14.52 [mu] M, which is superior to the current commercial algicide prometryn, and has the safety to human bodies, so that the closantel compound can be used as an effective component of the algicide to be applied to comprehensive treatment of cyanobacteria bloom, and has a good application prospect in the comprehensive treatment of cyanobacteria bloom. The application field of the closantel compound is also widened.

Description

Technical Field

[0001] The present application relates to the technical fields of algaecides, environmental protection, water pollution treatment and aquaculture, and in particular to the application of closantel compounds in inhibiting the growth of cyanobacteria. Background Art

[0002] Cyanobacteria are the oldest photosynthetic oxygen-releasing microorganisms on earth. They are widely distributed and have strong adaptability. In recent years, with the development of society, global industrialization and climate warming have become increasingly serious, leading to eutrophication of water bodies and causing large-scale outbreaks of cyanobacterial blooms around the world. The outbreak of cyanobacterial blooms will reduce the stability and diversity of other aquatic organisms in the water body, and will also cause some toxic cyanobacteria in lakes, rivers, and drinking water sources to multiply and produce metabolic toxins (such as microcystins). These toxins enter the human body through drinking water, thus seriously endangering human health. It is particularly urgent to effectively solve the problem of cyanobacterial blooms.

[0003] At present, the use of chemical algaecides to inhibit the growth of cyanobacteria or kill cyanobacteria is an important means of prevention and control to quickly and effectively solve the problem of cyanobacteria blooms. Among the existing chemical algaecides, there are heavy metal algaecides represented by copper sulfate, strong oxidant algaecides represented by potassium permanganate and peroxide, and herbicide algaecides represented by diuron and promethazine. However, these chemical algaecides are not specifically designed for algae, have poor selectivity, are highly toxic to aquatic plants and animals and beneficial microorganisms in water bodies, and may cause heavy metal pollution and damage the ecological environment, which greatly limits the full play of the effectiveness of using chemical algaecides to prevent and control algae.

[0004] Closantel sodium is also known as closantel sodium salt and closantel sodium salt. It belongs to salicylanilide compounds and is a new broad-spectrum antiparasitic drug currently used in aquaculture, showing high safety to the human body. However, at present, the scope of application of closantel compounds is only parasiticides. The inhibitory effect of closantel compounds on cyanobacteria has not been reported. The purpose of the present invention is to discover the inhibitory effect of these compounds on cyanobacteria and possible inhibitory mechanisms, and provide the application of closantel compounds in inhibiting the growth of cyanobacteria. Summary of the invention

[0005] The purpose of the present application is to provide an application of closantel compounds in inhibiting the growth of cyanobacteria. Closantel compounds have a good inhibitory effect on cyanobacteria and are safe to the human body. They can be used as an effective ingredient of an algaecide in the comprehensive management of cyanobacterial blooms.

[0006] In order to solve the above technical problems, the technical solution adopted in this application is:

[0007] The present application provides the use of closantel compounds in inhibiting the growth of cyanobacteria, which inhibits the EC of 5 species of cyanobacteria.50 The five cyanobacteria are Microcystis aeruginosa.FACHB905, Synechocystis sp.PCC6803, Oscillatoria sp.FACHB528, Aphanizomenon sp.FACHB1395, and Nostoc sp.FACHB892.

[0008] Target-based rug design (TBDD) has attracted much attention due to its many advantages such as high selectivity, high efficiency and safety for non-target organisms, and has become an important means of drug and pesticide development in recent years. Fructose-1,6-bisphosphate / sedoheptulose-1,7-bisphosphatase (Cy-FBP / SBPase) is an important regulatory enzyme in the photosynthesis system of cyanobacteria. It exists in the dark reaction phase of photosynthesis and is a bifunctional hydrolase that can hydrolyze fructose-1,6-phosphate (FBP) and sedoheptulose-1,7-phosphate (SBP) into fructose-6-phosphate and sedoheptulose-7-phosphate, respectively. When Cy-FBP / SBPase mutates, it will cause the photosynthesis of cyanobacteria to be severely inhibited until the cyanobacteria die. It has the key characteristics of being a target enzyme to screen highly selective cyanobacterial inhibitors. The present application found that closantel compounds have excellent inhibitory effects on Cy-FBP / SBPase and can be used as cyanobacterial Cy-FBP / SBPase inhibitors. It is inferred that closantel compounds inhibit cyanobacteria by inhibiting Cy-FBP / SBPase and thereby inhibiting cyanobacterial photosynthesis.

[0009] Compared with the prior art, the embodiments of the present application have at least the following advantages or beneficial effects:

[0010] 1. The present application shows through the cyanobacterial fructose 1,6-bisphosphate / sedoheptulose-1,7-bisphosphatase enzyme body experiment that closantel compounds have a good inhibitory effect on cyanobacterial fructose 1,6-bisphosphate / sedoheptulose-1,7-bisphosphatase, and its inhibitory IC 50 The concentration of chloranil is 0.16±0.01μM~15.3±1.7μM, which can be used to inhibit the activity of cyanobacterial fructose 1,6-bisphosphate / sedoheptulose-1,7-bisphosphatase. Therefore, closantel compounds can be used as drugs targeting Cy-FBP / SBPase in the field of cyanobacteria control.

[0011] 2. The present application shows through the blue algae growth inhibition experiment that the closantel compounds have good inhibitory effects on 5 blue algae in the phylum Cyanobacteria. 1 For ONa, R 5 is methyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 For example, compound I-1 inhibited the EC of various cyanobacteria. 50 The concentration of chloranil in the algae is 0.46-14.52 μM, and the effect on Microcystis aeruginosa is more than 6 times better than that of the current commercial algaecide promethazine, and it is safe for human body. Therefore, chloranil compounds can be used as the effective ingredients of algaecides in the comprehensive control of cyanobacterial blooms, which also broadens the application field of chloranil compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the embodiments will be briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present application and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without paying creative work.

[0013] Figure 1 The IC of the closantel compound I-1 of Example 2 of the present application on fructose 1,6-diphosphate / sedoheptulose-1,7-diphosphatase 50 picture;

[0014] Figure 2 This is a molecular docking diagram of the closantel compound I-1 of Example 3 of the present application and fructose 1,6-diphosphate / sedoheptulose-1,7-diphosphatase;

[0015] Figure 3 The EC of closantel compound I-1 against Microcystis aeruginosa 905 in Example 4 of the present application 50 picture.

[0016] Figure 4 This is a direct graph showing the inhibition of the closantel compound I-1 of Example 5 of the present application on Microcystis aeruginosa 905.

[0017] Figure 5 This is a graph showing the effect of the closantel compound I-1 of Example 5 of the present application on the chlorophyll a of Microcystis aeruginosa 905. DETAILED DESCRIPTION

[0018] In order to make the purpose, technical scheme and advantages of the embodiments of the present application clearer, the technical scheme in the embodiments of the present application will be described clearly and completely below. If the specific conditions are not specified in the embodiments, they are carried out according to the conventional conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0019] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present application will be described in detail below with reference to specific embodiments.

[0020] Application of closantel compounds in inhibiting the growth of cyanobacteria.

[0021] In some embodiments of the present application, the structural formula of the above-mentioned closantel compound is shown in Formula I:

[0022]

[0023] Wherein, the formula I is selected from at least one of the following compounds:

[0024] Compound I-1, wherein R 1 For ONa, R 5 is methyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 Independently selected from H or CH3;

[0025] Compound I-2, wherein R 1 For ONa, R 5 Ethyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 Independently selected from H or CH3;

[0026] Compound I-3, wherein R 1 For ONa, R 5 is n-propyl, R 9 Cl, R 2 , R 3 , R 4, R 6 , R 7 , R 8 , R 10 , R 11 Independently selected from H or CH3;

[0027] Compound I-4, wherein R 1 For ONa, R 5 is n-butyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 Independently selected from H or CH3;

[0028] Compound I-5, wherein R 1 OK, R 5 is methyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 Independently selected from H or CH3;

[0029] Compound I-6, wherein R 1 OK, R 5 Ethyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 Independently selected from H or CH3;

[0030] Compound I-7, wherein R 1 OK, R 5 is n-propyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 Independently selected from H or CH3;

[0031] Compound I-8, wherein R1 OK, R 5 is n-butyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 Independently selected from H or CH3.

[0032] In some embodiments of the present application, the closantel compounds inhibit the growth of cyanobacteria by inhibiting the activity of cyanobacterial fructose 1,6-diphosphate / sedoheptulose-1,7-diphosphatase.

[0033] In some embodiments of the present application, the compound used in the specific experiment is closantel compound I-1. 1 For ONa, R 5 is methyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 is H, and the structural formula is shown in Formula II:

[0034]

[0035] IC of the compound of formula II for the inhibition of cyanobacterial fructose 1,6-bisphosphate / sedoheptulose-1,7-bisphosphatase 50 It is 15.3±1.7μM.

[0036] In some embodiments of the present application, closantel compounds are used to inhibit EC 50 The concentration of cyanobacteria is 0.46-14.52 μM, and the cyanobacteria include Microcystis aeruginosa, Synechocystis, Oscillatoria, Aphanizomenon and Nostoc.

[0037] In some embodiments of the present application, the compound of formula II exhibits the best inhibitory effect on Microcystis aeruginosa 905, EC 50 The value was 0.46±0.33μM, which is better than the current commercial algaecide promethazine (EC 50 :3.18±0.13μM) more than 6 times, and is safe for humans.

[0038] The features and performance of the present application are further described in detail below in conjunction with the embodiments.

[0039] Example 1

[0040] In this example, closantel compounds were subjected to a cyanobacterial fructose 1,6-diphosphate / sedoheptulose-1,7-diphosphatase inhibition test and a Microcystis aeruginosa 905 activity inhibition test.

[0041] The cyanobacterial fructose 1,6-bisphosphate / sedoheptulose-1,7-bisphosphatase hydrolyzes fructose-1,6-bisphosphate into fructose-6-phosphate and inorganic phosphate. Therefore, the activity of the cyanobacterial fructose 1-6-bisphosphate / sedoheptulose-1,7-bisphosphatase can be determined by measuring the increase in inorganic phosphate, thereby reflecting the inhibition efficiency of the above-mentioned closantel compounds as inhibitors.

[0042] The reaction buffer system for determining the activity of fructose 1,6-bisphosphate / sedoheptulose-1,7-bisphosphatase contains 50mMTris-HCl (pH 8.3), 10mM dithiothreitol (DTT), and 15mM MgCl2. The inhibitor concentrations are 100, 60, 30, 10, 6, 3, and 1μM. 5mM substrate fructose 1,6-bisphosphate was added, the reaction temperature was 37°C, and the reaction time was 5min. The light absorption value at a wavelength of 620nm was detected using a multifunctional microplate reader. The inhibition rate was calculated by the formula = (V0-V i ) / V0×100%, where V0 is the reaction rate of the enzyme without adding inhibitor, V i The inhibition rate of different closantel compounds on fructose 1,6-bisphosphate / sedoheptulose-1,7-bisphosphatase at 50 μM is shown in Table 1.

[0043] Microcystis 905 is an algae that is extremely harmful when blue algae blooms, and is also a commonly used experimental algae species in the laboratory. Therefore, Microcystis 905 was selected as the living experimental subject. Microcystis 905 was cultured in BG-11 (+N) liquid culture medium containing different concentrations of compounds and cultured in an artificial climate incubator. The incubator temperature was controlled at 28℃±1℃, humidity was 60%, light intensity was 6000lx, 12h (light): 12h (dark), vibration mode, and manual shaking 3 times a day.

[0044] The specific operations are as follows:

[0045] 1. Pre-culture a batch of Microcystis 905, wait for 4-7 days of growth to the logarithmic phase, measure OD680, and inoculate for use;

[0046] 2. Dilute the above-mentioned logarithmic phase algae solution with fresh BG-11 (+N) medium to obtain inoculated algae solution, and control the algae cell concentration to about 1×10 6 Pieces / mL;

[0047] 3. Weigh the compound in advance, dissolve it with DMSO, and prepare different concentrations of the compound. Add 198 μL of the diluted inoculated algae solution to each well of the 96-well plate, and then add 2 μL of a certain concentration of the compound. Make 5 groups of compounds at each concentration in parallel, and set up a blank control without the compound (DMSO is added to the algae solution system) and a compound background control (the compound system prepared by dissolving in DMSO);

[0048] 4. After culturing in an artificial climate incubator for 7 days, measure OD680 with an enzyme marker and calculate the inhibition rate of compounds at different concentrations;

[0049] Inhibition rate calculation formula:

[0050] Growth inhibition rate = [blank control group OD680 - (experimental group OD680 - compound background control group OD680)] × 100 / blank control group OD680;

[0051] 5. Plot the concentration of the compound as the horizontal axis and the growth inhibition rate as the vertical axis. Use the logistic fitting formula in Origin to obtain the EC of closantel compounds. 50 The results are shown in Table 1.

[0052] Table 1 Activity of closantel compounds against Cy-FBP / SBPase and Microcystis aeruginosa

[0053]

[0054]

[0055] Example 2

[0056] This example is for the compound of formula II (closantel compound I-1. Wherein, R 1 For ONa, R 5 is methyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 For H), cyanobacterial fructose 1,6-bisphosphate / sedoheptulose-1,7-bisphosphatase inhibition assay was performed.

[0057]

[0058] The same test method as in Example 1 was used to test the IC values ​​of compounds at different concentrations for fructose 1,6-bisphosphate / sedoheptulose-1,7-bisphosphatase. 50 See Figure 1 ,from Figure 1 It can be seen that its IC 50 It is 15.3±1.7μM.

[0059] Example 3

[0060] In this example, a molecular docking experiment was performed between the compound of formula II (same as in Example 2) and cyanobacterial fructose 1,6-diphosphate / sedoheptulose-1,7-diphosphatase using computer-assisted software.

[0061] Cy-FBP / SBPase (PDB number: 3RPL) was downloaded from the protein crystal PDB database. The compound of formula II was docked with Cy-FBP / SBPase using SYBYL-X2.1.1 software. The ONIOM binding energy of the conformation (xB97X-D[1] / 6-31G*:PM6[2]:Amber[3]) was calculated. The 10 conformations with the lowest binding energy were further optimized and their single-point energies were calculated. Finally, the conformation with the lowest single-point energy calculated by XO was used as the optimal binding mode of the small molecule inhibitor with Cy-FBP / SBPase. The optimal binding mode is shown in Figure 2 ,from Figure 2 It can be seen that the multiple interactions between the compound of formula II and the key amino acid residues of Cy-FBP / SBPase jointly block the catalytic process of the substrate FBP.

[0062] Example 4

[0063] In this example, the compound of formula II (same as in Example 2) was tested for inhibiting the growth of Microcystis 905 at the algal level.

[0064] The same test method as in Example 1 was used to plot the concentration of the compound as the abscissa and the growth inhibition rate as the ordinate. The EC value of the compound of formula II was obtained by using the logistic fitting formula in Origin. 50 Values, such as Figure 3 shown.

[0065] The same research method was adopted, different cyanobacteria (Microcystis aeruginosa.FACHB905, Synechocystis sp.PCC6803, Oscillatoria sp.FACHB528, Aphanizomenon sp.FACHB1395, Nostoc sp.FACHB892) were used for culture test, and the traditional algaecide Prometryn was used as a comparison. The results of the compound of formula II on the five cyanobacteria are shown in Table 2.

[0066] Table 2 EC values ​​of compound II and Prometryn against five cyanobacteria 50 value

[0067]

[0068] From Table 2, we can see that the EC values ​​of the compound of formula II against five cyanobacteria are 50 The values ​​are between 0.46 and 14.52 μM, and its inhibition EC50 for Microcystis aeruginosa FACHB 905 is 0.46 μM, which is more than 6 times better than the traditional algaecide promethazine.

[0069] Example 5

[0070] Microcystis aeruginosa 905, which has the largest frequency and amplitude of cyanobacterial blooms, was selected as the algaecidal experimental object in the amplification system.

[0071] In the clean bench, dilute the two algae solutions with fresh BG11 culture medium to an OD of 680 =0.1 (the number of cells is 1×10 8 cell / L, equivalent to the cell density measured during the severe bloom period of Taihu Lake), the diluted algae solution was divided into 250mL conical flasks (100mL / bottle), and a certain concentration of the compound of formula II (same as Example 2) was added to the algae solution to make the final concentration of the compound 0, 1, 5, 10, 50, 100μM, and at the same time, Prometryn with a final concentration of 5μM was used as a positive control, and the algae solution cultured in BG11 was used as a control group. The culture was carried out in an artificial climate incubator with a light / dark cycle of 12h:12h at 28℃, and the algae growth was monitored by taking pictures, and the algae solution was taken regularly to determine chlorophyll a (Chla), and the inhibition rate was calculated.

[0072] The results are as follows Figure 4 and Figure 5 shown.

[0073] in Figure 4 The graph shows the intuitive inhibitory effect of different concentrations of the compound of formula II on Microcystis aeruginosa 905. The algae in the BG11 group grew normally. The negative control group added the same volume of solvent DMSO as the compound, which also showed no obvious effect on the growth of MaFACHB905. The positive control group was 5 μM of promethazine. The algae inhibition effect of the sodium compound of formula II gradually increased with the increase of concentration. Compared with promethazine, the algae inhibition effect of 5 μM of the compound of formula II was slightly superior. When the concentration was above 10 μM, it was observed that the growth of Microcystis was significantly inhibited. As the treatment time increased, the algae in the group treated with the compound of formula II gradually died, and the color of the algae solution turned white. From the intuitive graph, the algae inhibition effect of the compound of formula II was better than that of the commercial herbicide promethazine.

[0074] Figure 5 The chlorophyll a content of the algae liquid was measured on days 0, 2, 4, 6, and 8. The BG11 group and the DMSO group entered the logarithmic growth phase from day 4 to 6, and the chlorophyll a content increased significantly. After day 6, they gradually entered the plateau phase, and the chlorophyll a content increased slowly. The chlorophyll a content of the group treated with promethazine showed a trend of first increasing and then decreasing. The chlorophyll a content of the group treated with the compound of formula II was significantly inhibited from day 2, and the Chla of the 10 μM treatment group was almost zero.

[0075] In summary, the application of the closantel compounds of the embodiments of the present application in inhibiting the growth of cyanobacteria has the following advantages:

[0076] 1. The present application shows through the cyanobacterial fructose 1,6-bisphosphate / sedoheptulose-1,7-bisphosphatase enzyme body experiment that closantel compounds have a good inhibitory effect on cyanobacterial fructose 1,6-bisphosphate / sedoheptulose-1,7-bisphosphatase. Taking the compound of formula II as an example, its IC 50 It is 15.3±1.7μM, which can be used to inhibit the activity of cyanobacterial fructose 1,6-bisphosphate / sedoheptulose-1,7-bisphosphatase. Therefore, closantel compounds can be used as drugs targeting Cy-FBP / SBPase in the field of cyanobacteria control.

[0077] 2. The experiment of inhibiting the growth of cyanobacteria showed that closantel compounds had good inhibitory effects on 5 cyanobacteria in the phylum Cyanobacteria. Taking the compound of formula II as an example, the EC of Microcystis aeruginosa was inhibited. 50 The value is 0.4±0.33μM, which is better than the current commercial algaecide promethazine (EC 50 :3.18±0.13μM) by more than 6 times, and it is safe for human body. Therefore, closantel compounds can be used as the effective ingredients of algaecides in the comprehensive management of cyanobacterial blooms, which also broadens the application field of closantel compounds.

[0078] The embodiments described above are part of the embodiments of the present application, rather than all of the embodiments. The detailed description of the embodiments of the present application is not intended to limit the scope of the present application for protection, but merely represents the selected embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without making creative work belong to the scope of protection of the present application.

Claims

1. Application of closantel compounds in inhibiting the growth of cyanobacteria.

2. The use of the closantel compound according to claim 1 in inhibiting the growth of cyanobacteria, characterized in that: The structural formula of the closantel compound is shown in Formula I: Wherein, the formula I is at least one selected from compounds I-1 to I-8: Compound I-1, wherein R 1 For ONa, R 5 is methyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 Each is independently selected from H or CH3; Compound I-2, wherein R 1 For ONa, R 5 Ethyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 Each is independently selected from H or CH3; Compound I-3, wherein R 1 For ONa, R 5 is n-propyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 Each is independently selected from H or CH3; Compound I-4, wherein R 1 For ONa, R 5 is n-butyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 Each is independently selected from H or CH3; Compound I-5, wherein R 1 OK, R 5 is methyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 Each is independently selected from H or CH3; Compound I-6, wherein R 1 OK, R 5 Ethyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 Each is independently selected from H or CH3; Compound I-7, wherein R 1 OK, R 5 is n-propyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 Each is independently selected from H or CH3; Compound I-8, wherein R 1 OK, R 5 is n-butyl, R 9 Cl, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , R 10 , R 11 Each is independently selected from H or CH3.

3. The use of the closantel compound according to claim 2 in inhibiting the growth of cyanobacteria, characterized in that: The closantel compounds achieve the purpose of inhibiting the growth of cyanobacteria by inhibiting the activity of cyanobacterial fructose 1,6-diphosphate / sedoheptulose-1,7-diphosphatase.

4. The use of the closantel compounds according to claim 3 in inhibiting the growth of cyanobacteria, characterized in that: The closantel compounds inhibit the IC of cyanobacterial fructose 1,6-diphosphate / sedoheptulose-1,7-diphosphatase 50 It is 0.16±0.01μM~15.3±1.7μM.

5. The use of the closantel compound according to claim 2 in inhibiting the growth of cyanobacteria, characterized in that: The closantel compounds inhibit EC 50 The concentration of cyanobacteria is 0.46-14.52 μM, and the cyanobacteria include Microcystis aeruginosa, Synechocystis, Oscillatoria, Aphanizomenon and Nostoc.

6. The use of the closantel compounds according to claim 5 in inhibiting the growth of cyanobacteria, characterized in that: The inhibitory EC of the closantel compounds on Microcystis aeruginosa FACHB905 50 It is 0.16±0.33μM~10.3±0.5μM.

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