Design,Sythesis And Evaluation Of Bacterial Quorum Sensing Inhibitors

There are more than 80 years since the discovery of antibiotics.The antibiotics are applicated in clinical widely.A lot of bacteria have possessed the antimicrobial resistance with using more and more antibiotics,for example,MRS A,NDM-1 et al.They have threatened to human heath seriously.It is relevant to highlight that of all the infectious diseases,at least 65%are linked to the biofilms formation of bacterial.We faced "No action taday,no cure tomorrow".Quorum sensing(QS)is first discoveried in V.fisher in 1970s.QS is a cell communication mechanism through detecting the minimal threshold stimulatory concentration of certain chemicals called aotoinducers activate specific receptors associated with transcription signals for controlling various biochemical processes,for example:biofilm formation,expression of virulence factors,luminescence et al.So far,QS has been discovery in more than 50 bacteria,incuding E.coil and P.aeruginosa.The QS inhibitories can reduce the bacterial antimicrobial resistance by blocking the biofilms.We researched QS using C.violaceum as bacterial model.N-sulfonyl homoserine lactone derivatives and 3-aminooxazolidin-2-one derivatives had been designed by Structure-activity relationship(SAR)and molecular docking.There were 68 target compounds have been synthesized,among which 65 compounds had not been reported.The ee value of compound SHL-14 was 99.2%,which demonstrated that N-sulfonyl homoserine lactone derivatives possessed high enantiomeric purities and did not occur in the conformational change and racemic.The structures of all the compounds were identified by methods of MS,1H-NMR and 13C-NMR.Pharmacodynamic evaluation of the synthesized target compounds was conducted by spot test method.The QS inhibitory activity of all the compounds had been evaluation.The result of test indicated that most of N-sulfonyl homoserine lactone derivatives and a part of 3-aminooxazolidin-2-one derivatives exhibited good QS inhibitory activities in C.violaceum.The activities of SHL-14,SHL-18,AOZ-11 and AOZ-12 were the best,which indicated that these compounds could be used as leads for further development.The SAR of target compounds was investigated according the biological screening,which is important for futhre research.