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Application of ellipticine hydrochloride in the preparation of drugs against suis streptolysin

A technology of ellipticine and Streptococcus suis, applied in the field of microbial infectious diseases and medicine, can solve problems such as inability to alleviate the impact, and achieve the effect of reducing the mutation rate and reducing damage

Active Publication Date: 2021-12-03
HUAZHONG AGRI UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although commonly used antibiotics can kill Streptococcus suis, they cannot alleviate the impact of Streptococcus suis STSLS on the body

Method used

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  • Application of ellipticine hydrochloride in the preparation of drugs against suis streptolysin
  • Application of ellipticine hydrochloride in the preparation of drugs against suis streptolysin
  • Application of ellipticine hydrochloride in the preparation of drugs against suis streptolysin

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Experimental program
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Effect test

Embodiment 1

[0031] (1) In a 96-well plate, 50 μL of 2% sheep red blood cells suspended in PBS was added to 50 μL of ellipticine hydrochloride (EH) serially diluted in PBS, and incubated at 37° C. for 1 hour, wherein, The concentrations of EH were 1, 2, 4, 8, 16, 32, 64, and 128 μg / mL, respectively, and 2.5% TritonX-100 was used as a positive control. Plates were then centrifuged at 500 g for 5 minutes and 50 μL of supernatant from each well of the assay plate was transferred to a fresh 96-well plate. Hemolysis was confirmed visually and by measuring absorbance at 543 nm.

[0032] see results figure 1 , ellipticine hydrochloride itself does not cause red blood cell hemolysis.

[0033] (2) Culture Streptococcus suis SC19 strain at 37° C. for 12 hours, centrifuge at 10,000 rpm at 4° C. for 10 minutes, and collect the supernatant. Different volumes of culture supernatant were added to phosphate buffered saline solution (PBS, pH 7.4) containing 2% defibrinated sheep blood (total volume 1 mL...

Embodiment 2

[0041] (1) During the docking process of SLY and EH, the molecular docking mode of SLY and EH was analyzed using AUTODOCK4.2. The crystal structure of SLY was obtained from the Protein Data Bank (PDB) http: / / www.rcsb.org / structure / 3HVN. The 2D and 3D structures of EH were drawn by ChemBioDraw Ultra 14.0 and ChemBio3D Ultra 14.0, respectively. Through computational simulation methods, the binding pockets of proteins and small molecules are predicted such as Figure 6 A, Ellipticine hydrochloride binds to the Pose1 region of the hemolysin protein. In addition, if Figure 6 As shown in B, 11 amino acids including amino acids I87, D86, L110, N112, D111, T195, K190, N50, T191, S374, and N82 form a very good hydrophobic pocket cavity, and the hydrophobic pocket forms a very good hydrophobic property with the small molecule plane. It has a good hydrophobic interaction mode and plays a dominant role in the interaction, and a good hydrogen bond is formed between amino acids S84, L11...

Embodiment 3

[0046] The mice used in the following experiments were seven-week-old female BALB / c mice purchased from China Three Gorges University. Animal experiments conformed to animal ethics, and all experiments were conducted under the guidance of the Animal Experiment Protection Supervision and Control Committee of Huazhong Agricultural University (HZAUMO-2019-011).

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Abstract

The invention discloses the application of ellipticine hydrochloride in the preparation of anti-sui streptolysin medicine, which belongs to the field of microbial infectious diseases and medicine. The present invention finds that ellipticine hydrochloride can neutralize the toxicity of suis streptolysin and has a protective effect on mice infected by Streptococcus suis. The ellipticine or a pharmaceutically acceptable salt thereof has applications in the preparation of anti-suihemolysin medicines and medicines for preventing or treating Streptococcus suis infection. The present invention discovers the new medicinal value of ellipticine hydrochloride, and provides a new prevention and treatment drug for Streptococcus suis infection; Toxic shock-like syndrome damage to the body.

Description

technical field [0001] The invention relates to the field of microbial infectious diseases and medicine, in particular to the application of ellipticine hydrochloride in the preparation of anti-suihemolysin medicine. Background technique [0002] Streptococcus suis is one of the most important zoonotic pathogens, which seriously threatens human health and the development of swine industry, causing significant economic losses worldwide. According to incomplete statistics, since the first case of Streptococcus suis infection in Denmark in 1968, more than 1,600 cases of human infection with Streptococcus suis have been reported. Streptococcus suis infection can lead to a variety of diseases, including sepsis, meningitis, endocarditis, arthritis, among which the highest mortality rate is the toxic shock-like syndrome (STSLS) caused by Streptococcus suis. STSLS is characterized by bacterial burden, inflammatory cytokine storm, multisystem organ failure, and ultimately acute host...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/475A61P31/04
CPCA61K31/475A61P31/04
Inventor 谭臣鲁浩刘曼莉王晨晨鲁文嘉李晓丹王湘如陈焕春
Owner HUAZHONG AGRI UNIV
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