Vre Resistant Phosphonic Acid Esters Target Enzyme Inhibitors And Beta Lactamase Detection Reagent Synthesis And Activity Of Study

According to the mechanism of VanX, the drug-resistant target enzyme from vancomycin-resistant Enterococci (VRE), structural features and the relationship between inhibitors’structure and their kinetics, combined with our previous obtained relationship of structures, optimized the inhibition model, a series diverse structure of the β-carbon side phosphonates VanX inhibitors have been designed and synthesized. Seven kinds of phosphonate inhibitors have been synthesized through multi-step reaction ultimately.The inhibitory activities of seven newly synthesized compounds toward VanX were determined in the IC50experiments. The results indicated that six kinds of compounds have effectively inhibitory activity, and the relationship between the simplification of β-substituent and the high inhibitory activitie of inhibitors was observed.Cephalosporin nitrocefin was synthesized by three-step reaction accroding a comprehensive survey of the relevant literature, optimization of the synthesis route. This route had shorter reaction steps, and the experiment was easy to operate. The final yield of the route is higher, which reached to32.3%, as compared to the literature reported. A novel cephalosporin nitrocefin-similar detection reagent was synthesized as well.The two compounds were tested through a series of biological experiments. They could be hydrolyzed by β-lactamase specifically, resulting in the beta-lactam ring open-loop and significant change of their intramolecular conjugate system, which made the UV-Vis spectra changed significantly, accompanied by a clear discoloration from bright yellow to dark red. In the subsequent detection of beta-lactamase containing bacterial strains, discoloration of all the bacterial strains were observed and seven kinds of strains could be detected rapidly. In summary, these two detection reagents can proper fit the specifity of beta-lactamases and have the characteristics of high stability, obvious discoloration, fast detection and low limits detection, which made them good beta-lactamase detection reagents.The two reagents have great significance in the detection of beta-lactamase induced antibiotic resistant bacterial strains and the guidance of clinical medication.