Synthetic method of QseC ligand derivatives with role of inhibiting bacterial virulence

Abstract

The invention discloses a synthetic method of QseC ligand derivatives capable of inhibiting bacterial virulence and an application. The QseC ligand derivatives are bacterial membrane surface protein QseC ligands and can be specifically combined with the QseC ligands and be used for retroregulation of a qseC-qseB-fliC-flhD gene pathway, thereby inhibiting the release of bacterial pathogenic virulence factors, reducing the bacterial virulence and the invasiveness during the bacterial infection and further achieving the role of controlling the harm of the bacterial infection; however, the QseC ligand derivatives do not affect normal growth and reproduction of bacteria, thereby avoiding the initiation of bacterial drug resistance pressure. The QseC ligand derivatives have the advantages of good anti-bacterial effect, low toxicity, good stability and difficult drug resistance. The QseC ligand derivatives synthesized by the optimized synthetic method of the QseC ligands and the chemical synthetic method of the derivatives thereof can be used for preparing novel broad-spectrum antibacterial drugs with resistance to multi-drug-resistant bacteria infection.

Description

technical field [0001] The invention relates to a synthesis method and application of a novel broad-spectrum antibacterial virulence compound QseC ligand derivative derivative, in particular to a synthesis method of the QseC ligand derivative. Background technique [0002] The quorum sensing system (QSS) is an information transmission system between bacteria. The system is capable of synthesizing and secreting autoinducer molecules (autoinducer, AI). AI reaches the outside of the cell through the diffusion or transport system. When the concentration of AI reaches a certain threshold with the density of the bacterial population, it can be recognized by the sensor protein located on the membrane and sense it. The cell density of the population ultimately initiates the expression of a specific target gene, and its expression product enables bacteria to adapt to various changes in the external environment. QSS is the most basic and necessary functional system for Gram-negative ...

AI Technical Summary

Problems solved by technology

It has been found that the LED209 series of compounds used for screening QseC ligands have high toxicity and poor water solubility, and are all polyheterocyclic connection products (Table 1), and have not yet been optimized and modified based on the structure of LED209 itself; At the same time, the screened compound LED209, because its spatial structure is most similar to the QseC endogenous ligand AI-3 or NE, can specifically bind to the bacterial membrane protein QseC and antagonize AI-3 or NE. LED209 needs to be prepared into a multi-component polymer to enhance solubility and bioavailability when administered p.o or iv, and there are limitations in clinical application

Images