Synthesis And In Vitro Antibacterial Activity Of Novel Fluoroalkyl-Substituted Pyrazolyl Oxazolidinones

Widespread use of antimicrobial drugs have led to a large number of bacteria serious problem of drug resistance, and bring medical huge problem worldwide. Many novel antibacterial compounds which having antimicrobial mechanisms have been developed. For example, linezolid is one of oxazolidinone antibacterial drugs, which received US FDA approval to market in 2000, and its main mechanism of action is to inhibit binding of mRNA ribosome, thus inhibiting bacterial protein synthesis.In this thesis, the mechanism of the aspect and structure-activity relationship of antibacterial oxazolidinone compounds were summarized, and a new series of fluorine-containing oxazolidinone compounds have been synthesized. The enol ethers, epichlorohydrin and fluorine-containing acid anhydride were used as starting materials, and a series of oxazolidinone heterocyclic compounds were synthesized and characterized. The minimum inhibitory concentration (MIC)of the target compounds were tested using plate dilution method. The target compounds were tested against Gram-positive bacterial pathogens including Staphylococcus aureus MRSA, Staphylococcus aureus MSSA, Staphylococcus epidermidis MRSE, epidermidis bacteria resistant strains MSSE, pneumococcus, enterococcus. The results showed that two target compounds have good activity as compared to linezolid. The two target compounds and linezolid were subjected to docking analysis using AutoDock. The target compounds showed btter binding energy than linezolid bound to 3DLL protein. In addition, the agricultural fugicidal activity of the target compounds have been evaluated against botrytis cinerea pathogen, watermelon anthracnose pathogen, rice sheath blight pathogen, and original rice blast. Our new compounds provide a new choice of the development of novel fungicides.