Design,Synthesis And Biological Evaluation Of Antagonists Of Bacterial Quorum Sensing

In recent years,with the discovery of new antibiotics slowing down,the abuse and overuse of broad-spectrum antibiotics,antibiotic resistance has become one of the issues that people are more and more concerned about.A lot of patients infected with bacteria can't be treated effectively and completely because of antibiotic resistance.In all diseases caused by bacteria,65%of bacterial infections is related to the formation of biofilms regulated by bacterial quorum sensing.Bacterial quorum sensing has gradually become one of the targets for many scholars.Bacterial quorum sensing is an intercellular communication mechanism,it includes the generation,release,and recognition response of signal molecules(autoinducer,AI).Autoinducer increases with the number of bacteria,when it reaches a certain threshold,it will be recognized by the corresponding transcriptional regulatory protein.It eventually leads to the formation of a capsule,bioluminescence,etc.Therefore,inhibition of bacterial quorum sensing can block the production of bacterial toxins and biofilms,reducing the bacterial resistance to antibiotics.At the same time it does not affect the normal physiological function and growth of normal cells.This article is based on the previous work,selected ZS-12 as lead compound.Using the principle of bio-estermination and the three-dimensional structural characteristics of the quorum-sensing transcriptional regulatory protein CviR,designed a series of 3-amino-2-oxazolidinone target compounds.We synthesized eighteen new target compounds by using bromocarboxylic acid esters and 3-amino-2-oxazolidone as raw materials.And the chemical structure was confirmed by 1H-NMR and MS.In this study,a mutant strain of Chromobacterium purpureus CV026 with a bacterial quorum sensing system is used as a model organism.To study the effect of target compounds on bacterial quorum sensing.The results showed that except for YXL-7,11,14,16,18 which have an agonistic effect on the growth of CV026 bacteria,the other target compounds all have different degrees of inhibition.Among them,YXL-13 had the strongest quorum-sensing inhibitory effect on CV026(IC50=3.68?M).In addition,an interesting result was found in the study,when the carbon chain of the target compound was extended to 7 carbon atoms,CV026 bacterial quorum sensing was switched from an inhibitor to an agonist.