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Application of aminothiazole compounds in preparation of medicine for treating toxoplasma gondii infection diseases

A technology for aminothiazole and infectious diseases, which is applied in the field of parasitic disease prevention and control, toxoplasma gondii prevention and control, and achieves the effect of excellent inhibition effect, inhibition of proliferation, and good application prospects

Pending Publication Date: 2021-10-19
LANZHOU INST OF ANIMAL SCI & VETERINARY PHARMA OF CAAS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, no studies have shown that ICA has inhibitory activity against Toxoplasma gondii

Method used

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  • Application of aminothiazole compounds in preparation of medicine for treating toxoplasma gondii infection diseases
  • Application of aminothiazole compounds in preparation of medicine for treating toxoplasma gondii infection diseases
  • Application of aminothiazole compounds in preparation of medicine for treating toxoplasma gondii infection diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 Indirect Immunofluorescence Determination of the Anti-Invasion Effect of ICA on Toxoplasma gondii RH

[0030] Step: Mix 1×10 containing each concentration of ICA 5 Individual / mL RH tachyzoites (type I virulent strains known in the art, which can be purchased from ATCC) were inoculated in monolayer Vero cells after being treated in an incubator for 1 h, and 0.25% DMSO was used as a negative control group (without ICA solvent control group), 10 μg / mL pyrimethamine (PYR) was used as a positive control. After 2 hours of invasion, try to wash away the non-invading tachyzoites with PBS. After fixation, antigen retrieval and blocking, the extracellular T. gondii was labeled with mouse anti-T. gondii monoclonal antibody, and the secondary antibody was goat anti-mouse IgG H&L (Alexa 647), after permeabilization with 0.2% Triton X-100, the rabbit anti-toxoplasma polyclonal antibody was selected to label the intracellular Toxoplasma gondii, and the secondary antibody ...

Embodiment 2

[0033] Example 2 Determination of the inhibitory effect of ICA on Toxoplasma gondii RH-2F tachyzoites by biochemiluminescence

[0034] Steps: Toxoplasma gondii type I virulent strain RH-2F expressing β-galactosidase was selected for growth inhibition assay. Harvest fresh and vigorous RH-2F tachyzoites from Vero cells, count on a hemocytometer, and adjust the concentration of RH-2F to 1×10 5 individual / mL. ICA of various concentrations was prepared in this way, and added to a white 96-well plate, with 0.25% DMSO as the control group (solvent control group without ICA), and the blank group (without ICA) containing only medium. After 12 hours of incubation, add As for the detection reagent, after 30 minutes of action, the luminescence value was detected in a photometer to calculate the survival rate of RH-2F.

[0035] Result: results like figure 2 , the inhibitory effect of ICA on RH-2F was dose-dependent. The higher the concentration of ICA, the lower the activity of RH-2F...

Embodiment 3

[0036] Example 3 Indirect Immunofluorescence Determination of the Antiproliferative Effects of ICA on Toxoplasma gondii RH and Pru

[0037] Method: Divide 1×10 5 RH tachyzoites / mL were inoculated in a single layer of Vero cells, and the non-invaded RH tachyzoites were washed away with DPBS after 4 hours of invasion, and then ICA with a concentration of 0.1 μg / mL was added for 24 hours and 48 hours, and a blank was set at the same time Control group (no ICA, medium only), negative control group and positive control group. After that, fixation, antigen retrieval, blocking and permeabilization were carried out, and Toxoplasma gondii antibody was selected to be labeled, and the secondary antibody was goat anti-rabbit IgG H&L (Alexa 488), DAPI stains nuclei. After staining and mounting, the slides were observed and photographed under a confocal microscope.

[0038] Will 1×10 5 Pru tachyzoites / mL were inoculated in the monolayer Vero cells in a 12-well plate, and after 6 hours of...

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Abstract

The invention relates to the technical field of parasitic disease prevention and treatment, and provides application of aminothiazole compounds in the preparation of a medicine for treating toxoplasma gondii infection diseases. It is found that the aminothiazole compounds have remarkable inhibitory activity on virulent or attenuated toxoplasma gondii of different genotypes and can inhibit proliferation of the toxoplasma gondii, and the inhibitory effect of the aminothiazole compounds is superior to that of an existing medicine pyrimethamine for treating the toxoplasma gondii. According to the invention, the medication spectrum of the aminothiazole compounds is developed, the effective medicine with low side effect is provided for treating acute and chronic toxoplasma infection, and the application prospect is good.

Description

technical field [0001] The invention relates to the technical field of parasitic disease prevention and control, in particular to the field of toxoplasma gondii prevention and control, and specifically provides the application of aminothiazole compounds in the preparation of medicines for treating toxoplasma gondii infection diseases. Background technique [0002] Toxoplasma belongs to the subphylum Apicomplexa, Sporozoa, Coccidia, Eucoccidia, Eimeria, Toxoplasma, Toxoplasma (Toxoplasma). There is only one species under the genus Toxoplasma, Toxoplasmagondii, commonly known as Toxoplasma gondii. However, according to different regions, different hosts, different virulence, life history and development time, etc., it can be divided into three different genotypes, type Ⅰ (RH and GT-1 strains), type Ⅱ (ME49 and Pru strain) and type III (CEP and VEG strains). The life cycle of Toxoplasma gondii is divided into 5 stages: tachyzoite stage (trophoblast): rapidly divides in the nu...

Claims

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Application Information

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IPC IPC(8): A61K31/4439A61P33/02
CPCA61K31/4439A61P33/02
Inventor 张继瑜邱燕华翟斌涛白玉彬王玮玮周绪正李冰杨枭荣魏小娟程富胜
Owner LANZHOU INST OF ANIMAL SCI & VETERINARY PHARMA OF CAAS
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