CN-121987605-A - Application of compound 3546847 in preparation of anti-staphylococcus aureus hemolysin medicine

Abstract

The invention discloses an application of a compound 3546847 in preparing a medicament for resisting staphylococcus aureus hemolysin, belonging to the fields of microbial infectious diseases and medicines. The invention discovers that the compound 3546847 can neutralize the toxicity of staphylococcus aureus hemolysin and has a protective effect on mice infected by MRSA staphylococcus aureus USA 300. The compound 3546847 has the application of preparing an anti-staphylococcus aureus hemolysin medicine and a medicine for preventing or treating staphylococcus aureus infection. The invention discovers a new medicinal value of the compound 3546847, provides a new prevention and treatment medicine for staphylococcus aureus infection, and the compound 3546847 can neutralize a main virulence factor of staphylococcus aureus, namely hemolysin, and reduce inflammatory injury.

Inventors

• DUAN ZHEN
• WANG AI
• CHEN XIAOHUI

Assignees

• 上海陶术生物科技股份有限公司

Dates

Publication Date

20260508

Application Date

20260113

Claims (9)

1. 1. The application of the compound 3546847 in preparing the anti-staphylococcus aureus hemolysin medicine is characterized in that the structure of the compound 3546847 is as follows: 。
2. 2. The application of the pharmaceutically acceptable salt of the compound 3546847 in preparing the anti-staphylococcus aureus hemolysin medicine is characterized in that the structure of the compound 3546847 is as follows: 。
3. 3. The application of compound 3546847 or pharmaceutically acceptable salt thereof in preparing a medicament for preventing or treating staphylococcus aureus infection is characterized in that the structure of compound 3546847 is as follows: 。
4. 4. the application of a composition containing a compound 3546847 or pharmaceutically acceptable salt thereof in preparing a medicament for preventing or treating staphylococcus aureus infection is characterized in that the structure of the compound 3546847 is as follows: 。
5. 5. The method of claim 4, wherein the composition further comprises an additional anti-Staphylococcus aureus active ingredient.
6. 6. The application of compound 3546847 or pharmaceutically acceptable salt thereof in preparing an antibacterial hemolysin medicament is characterized in that the structure of compound 3546847 is shown as follows: 。
7. 7. The application of compound 3546847 or pharmaceutically acceptable salt thereof in preparing a medicament for preventing or treating hemolysin-producing bacterial infection is characterized in that the structure of compound 3546847 is as follows: 。
8. 8. The application of a composition containing a compound 3546847 or pharmaceutically acceptable salt thereof in preparing a medicament for preventing or treating a hemolysin-producing bacterial infection is characterized in that the structure of the compound 3546847 is shown as follows: 。
9. 9. the method of claim 8, wherein the composition further comprises an additional active ingredient against a hemolysin producing bacterium.

Description

Application of compound 3546847 in preparation of anti-staphylococcus aureus hemolysin medicine Technical Field The invention belongs to the fields of microbial infectious diseases and medicines, and particularly relates to application of a compound 3546847 in preparation of a medicine for resisting staphylococcus aureus hemolysin. Background Staphylococcus aureus, one of the bacteria of Multiple Drug Resistance (MDR) and broad drug resistance (XDR), is a 30% asymptomatic plant for humans, and is the most dangerous species among all staphylococci. Currently, methicillin-resistant staphylococcus aureus (MRSA) causes more than 10-fold more infection than the sum of all multi-drug resistant (MDR) gram-negative pathogen infections. Alpha-hemolysin is the most well known toxin of staphylococcus aureus, and can disrupt cell membrane structure and cause apoptosis in human monocytes, T cells and B cells. Although the common antibiotics can kill staphylococcus aureus, the influence of inflammation caused by staphylococcus aureus on organisms cannot be relieved, and the search for a medicament capable of antagonizing staphylococcus aureus hemolysin is a key for treating staphylococcus aureus infection. Disclosure of Invention The invention aims to provide a novel application of a compound 3546847, namely an application of a compound 3546847 in preparing medicines for resisting staphylococcus aureus hemolysin. The structural formula of the compound 3546847 is shown as follows: the aim of the invention is achieved by the following technical scheme: The invention discovers that the compound 3546847 can neutralize the toxicity of staphylococcus aureus hemolysin and has a protective effect on mice infected by staphylococcus aureus. Based on this, the invention provides the following applications: use of compound 3546847 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament against staphylococcus aureus haemolysin. Use of compound 3546847 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the prevention or treatment of a staphylococcus aureus infection. Use of a composition comprising compound 3546847 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the prevention or treatment of a staphylococcus aureus infection. The composition may contain other active ingredients against staphylococcus aureus in addition to compound 3546847 or a pharmaceutically acceptable salt thereof, and may further contain a pharmaceutically acceptable carrier. Use of compound 3546847 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for combating bacterial hemolysin. Use of compound 3546847 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the prevention or treatment of a haemolysin-producing bacterial infection. Use of a composition comprising compound 3546847 or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the prevention or treatment of a haemolysin-producing bacterial infection. The composition may comprise, in addition to compound 3546847 or a pharmaceutically acceptable salt thereof, other active ingredients against hemolysin producing bacteria, and may further comprise a pharmaceutically acceptable carrier. The invention has the following advantages and beneficial effects: (1) The invention discovers a new medicinal value of the compound 3546847 and provides a new prevention and treatment medicament for staphylococcus aureus infection. (2) The compound 3546847 can neutralize alpha-hemolysin which is a main virulence factor of staphylococcus aureus, and reduce the damage of inflammation to organisms. (3) Compound 3546847 acts by neutralizing bacterial virulence factors, reducing bacterial variability. Drawings FIG. 1 is a statistical plot of the haemolytic toxicity of compound 3546847 on red blood cells. FIG. 2 is a statistical plot of the results of lysis of erythrocytes by Staphylococcus aureus USA300 culture supernatant. FIG. 3 is a statistical plot of the results of inhibition of hemolytic activity of Compound 3546847 on Staphylococcus aureus USA300 culture supernatant. FIG. 4 is a statistical plot of the results of inhibition of hemolytic activity of compound 3546847 against Staphylococcus aureus USA300 hemolysin protein. FIG. 5 is a schematic representation of the molecular docking pattern of Staphylococcus aureus alpha-hemolysin with compound 3546847, A the docking conformation of 7AHL with 3546847, B the highest affinity conformation of hemolysin with 3546847, C the interaction between hemolysin and 3546847. FIG. 6 is a graph showing a thermal reaction fit of compound 3546847 to a hemolysin protein. Fig. 7 is a graph of survival of staphylococcus aureus USA300 infected mice treated with compound 3546847 and untreated. FIG. 8 is a graph showing the results of IL-6 and TNF- α detection in mouse serum. FIG. 9 is a graph showing the results of