Medical application of 5-iodothymidine in preparation of medicine for resisting chicken coccidiosis

Abstract

The invention discloses a medical application of 5-iodothymidine in preparation of an anti-chicken coccidiosis drug, which can be used for preparing the anti-chicken coccidiosis drug, solves the problem of serious drug resistance of the anti-coccidiosis drug in the current poultry raising industry, verifies the effect of the 5-iodothymidine in the anti-chicken coccidiosis drug, can be used for preparing the anti-coccidiosis drug or aims at resisting the coccidiosis, and can be used for preparing the anti-chicken coccidiosis drug. When the compound is added into feed and drinking water, a new lead compound is provided for research and development of anti-coccidiosis drugs.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, discloses the medical use of 5-iodothymidine in preparing an anti-chicken coccidiosis drug, and has obvious medical effects. Background Art

[0002] Chicken coccidiosis is a parasitic disease caused by Eimeria coccidia parasitizing the chicken intestines. It has a significant impact on my country's poultry industry and is classified as a Class III animal disease. Among them, Eimeria tenella ( Eimeria tenella ) is the most pathogenic species of Eimeria. Chicken coccidiosis primarily infects chicks, with a mortality rate as high as 80%. Adult chickens are often latently infected. Infected birds exhibit bloody stools, emaciation, loss of appetite, and severe damage to the intestinal mucosa, leading to reduced feed conversion rates and stunted growth, causing significant economic losses to the livestock industry. Its spread relies on oocyst contamination and is particularly prone to outbreaks in high-temperature, high-humidity, and high-density stocking conditions.

[0003] At present, drug control is an important means of preventing and controlling chicken coccidiosis. Anticoccidial drugs mainly include antibiotics and chemical synthetic drugs. Although these anticoccidial drugs have achieved certain results in the prevention and control of coccidiosis, the problem of drug resistance is becoming increasingly prominent, and there is an urgent need to develop new anticoccidial drugs.

[0004] The present invention relates to 5-iodothymidine (7-Deaza-7-iodoadenosine), also known as 5-iodotuberculin, with a molecular weight of 392.15, a CAS number of 24386-93-4, and a molecular formula of C 11 H 13 N₄O₄ is characterized by its rich biological activity. As a broad-spectrum kinase inhibitor, 5-iodothymidine can affect cell proliferation and survival. Specifically, as an inhibitor of adenosine kinase, it can inhibit the proliferation of colon cancer cells and induce apoptosis. Furthermore, 5-iodothymidine exhibits potent inhibitory and even bactericidal effects against various fungi, significantly inhibiting biofilm and hyphae formation and significantly damaging mature biofilms. Currently, there are no studies on the application of 5-iodothymidine in the treatment of chicken coccidiosis. Summary of the Invention

[0005] The present invention provides application of 5-iodothymidine in preparing an anti-chicken coccidiosis drug, and also provides an anti-chicken coccidiosis drug. The drug contains 5-iodothymidine as an active ingredient as a main component.

[0006] The present invention discloses the medical use of 5-iodothymidine in the preparation of an anti-coccidiosis drug. Through molecular docking analysis experiments between 5-iodothymidine and targets related to coccidiosis and analysis of the effect of anti-coccidiosis infection, it is disclosed that 5-iodothymidine has the therapeutic use of anti-coccidiosis infection.

[0007] The positive effects of the present invention are: disclosing a new medical use of 5-iodothymidine, which can be used to prepare drugs against chicken coccidiosis, solving the serious drug resistance problem of anticoccidial drugs in the current poultry industry, and confirming the effect of 5-iodothymidine in treating chicken coccidiosis. The present invention can be used to prepare drugs against chicken coccidiosis, or added to feed or drinking water for the purpose of treating coccidiosis, thereby providing a new lead compound for the research and development of anticoccidial drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 , the binding energy of 5-iodothymidine provided by the present invention for docking with targets related to chicken coccidiosis; Figure 2 , Schematic diagram of the docking of 5-iodothymidine and EGFR provided by the present invention. DETAILED DESCRIPTION

[0009] The present invention is further described by way of examples below, which do not limit the present invention in any way. Without departing from the technical solution of the present invention, any modification or alteration of the present invention that can be easily implemented by a person skilled in the art will fall within the scope of the claims of the present invention.

[0010] Example 1: Molecular docking analysis of 5-iodothymidine and chicken coccidiosis-related targets 1. Analysis of disease targets related to chicken coccidiosis: The transcriptome data of chicken cecal tissue infected with Eimeria tenella (GSM5087811, GSM5087812, GSM5087813, GSM5087814, GSM5087815, and GSM5087816) were retrieved through the SRA sub-database of the NCBI database. The differential gene targets were analyzed using RNA-Seq tools to obtain targets related to chicken coccidiosis. 2. Prediction and screening of 5-iodothymidine targets and targets that overlap with chicken coccidiosis-related diseases: The SMILE number of 5-iodothymidine was searched in the Pubchem database (http: / / pubchem.ncbi.nlm.nih.gov / ), and its drug targets were predicted using the SwissTargetPrediction database. Potential targets (Probability > 0) were screened and retained. The drug targets of 5-iodothymidine were compared with disease targets related to chicken coccidiosis to identify overlapping targets between the two. 3. Molecular docking: 5-iodothymidine and its corresponding chicken coccidiosis-related target protein were selected for molecular docking. The 2D structure of the small molecule ligand was obtained through the PubChem database, and the 2D structure was input into the Chem Office software to generate its 3D structure. The RCSB PDB database was used to screen the protein target and the crystal structure with high resolution was used as the molecular docking receptor. The protein was dehydrated and dephosphorylated using the PyMOL software. The Molecular Operating Environment software was used to minimize the energy of the compound, pre-process the target protein and search for active pockets. Finally, MOE 2019 was run for molecular docking, and the number of operations was set to 50. The binding activity of the two was evaluated based on the binding energy, and the results were visualized using PyMOL and Discovery studio software. result: Through comparison, five intersection targets related to 5-iodothymidine and chicken coccidiosis were screened out: CA7, ADORA2A, CA4, PTGS2, and EGFR; The binding energy of 5-iodothymidine docking with chicken coccidiosis-related targets is as follows Figure 1 As shown in the figure, the lower the binding energy, the stronger the binding activity of 5-iodothymidine to the target. The results show that the molecular docking energy range is -5.11~-7.39kcal / mol. It is generally believed that a docking energy value of <-4.25 kcal / mol indicates a certain binding activity between the two, <-5.0 kcal / mol indicates good binding activity, and <-7.0 kcal / mol indicates strong binding activity. The results show that one docking group has strong binding activity, and four docking groups have good binding activity. Among them, Asp855, Lys745, and Met793 on the EGFR protein receptor form hydrogen bond interactions with 5-iodothymidine, and residues Ala743 and Met793 form hydrophobic interactions with 5-iodothymidine. In addition, Val726 in the protein forms a Pi-Sigma interaction with the compound (such as Figure 2 shown).

[0011] Example 2: Analysis of the effect of 5-iodothymidine on chicken coccidiosis infection One hundred and eighty seven-day-old chicks were randomly divided into the following six groups: G1 as a blank control group, G2 as an infection control group, G3 as a conventional drug control group, G4 as a 10 mg / L group, G5 as a 1 mg / L group, and G6 as a 100 μg / L group. At 14 days of age, each chick in each group except group G1 was orally infected with 5×104 oocysts. After infection with coccidian oocysts, diclazuril solution was added to the drinking water of group G3, and different concentrations of 5-iodothymidine were added to the drinking water of groups G4, G5, and G6, respectively, to ensure sufficient drinking water for 7 consecutive days. The specific grouping and treatment are shown in Table 1.

[0012] Table 1

[0013] The mental state and fecal status of the chickens were observed and recorded daily. Dead chicks were weighed and necropsied. If death was caused by coccidia infection, the lesion score was 4 points. All chicks were weighed, necropsied, and scored for cecal lesions on the 8th day after infection. Feces of each group were collected to calculate the number of oocysts. Evaluation criteria for anticoccidial index (ACI): ACI = (relative weight gain + survival rate) - (cecal lesion value + oocyst value), judgment criteria: ACI ≥ 180 is a high-efficiency anticoccidial level, 140 ≤ ACI < 180 is a moderate-efficiency anticoccidial level, 120 ≤ ACI < 140 is a low-efficiency anticoccidial level, and ACI < 120 is ineffective; relative weight gain (%) = (average weight gain of the experimental group / average weight gain of the blank group) × 100%; survival rate = number of survivors before sacrifice / number of survivors before infection × 100%; oocyst value It is calculated from the number of oocysts per gram of feces (OPG); the cecal lesions of each group of chicks are scored according to the following lesion scoring standards: 0 points: normal, no macroscopic lesions; 1 point: there are a small number of scattered petechiae on the cecal wall, the intestinal wall is not thickened, and the contents are normal; 2 points: there are a large number of lesions, the cecal contents are obviously bloody, the cecal wall is slightly thickened, and the contents are normal; 3 points: there is a lot of blood or cecal cores in the cecum, and the cecal wall is obviously thickened; 4 points: the cecum is swollen due to being filled with a large amount of blood or intestinal cores. When the cecal lesions on both sides are inconsistent, the more serious side shall prevail. The cecal lesion value of each group of chicks is calculated according to the following formula: Lesion value = average lesion score × 10; result: Clinical symptom observation: On day 4 after inoculation with coccidian oocysts, chickens in the control group (G2), the 1 mg / L 5-iodothymidine group (G5), and the 100 μg / L 5-iodothymidine group (G6) showed lethargy, with their necks tucked in and eyes closed, their feathers disheveled, and their appetites decreased. On day 6, chickens in G2, G5, and G6 developed bloody stools, and deaths occurred in G2, the 10 mg / L 5-iodothymidine group (G4), G5, and G6. Chickens in the remaining groups showed no abnormalities. The anticoccidial index for each group was calculated, and the results are shown in Table 2. Table 2

[0014] As shown in Table 2, the anticoccidial index of the 10 mg / L 5-iodothymidine (G4) group was 138.67, which had a low anticoccidial level.

[0015] in conclusion In summary, 5-iodothymidine has therapeutic uses against coccidial infection in chickens and can be used to prepare drugs against coccidiosis, or added to feed or drinking water for the purpose of treating coccidiosis.

Claims

The medical use of 1.5-iodothymidine in the preparation of drugs against chicken coccidiosis.

2. The use according to claim 1, characterized in that The pathogen of chicken coccidiosis is Eimeria coccidia, and the Eimeria coccidia is Eimeria tenella.

3. An anti-chicken coccidiosis drug, characterized in that: A medicine containing 5-iodothymidine as an active ingredient and a medicine composition thereof.

4. An anti-chicken coccidiosis drug according to claim 3, characterized in that, The medicament further comprises one or more carriers.

5. An anti-chicken coccidiosis drug according to claim 4, characterized in that, The carrier includes pharmaceutically acceptable diluents, wetting agents, adhesives, flash disintegrating agents, lubricants, color and flavor regulators, solvents, solubilizers, cosolvents, emulsifiers, antioxidants, metal complexing agents, preservatives, pH regulators, surfactants, excipients, fillers, and synergists.

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