Studies On Synthesis And Biological Activity Of 2-substituted Of Cephalosporin New Compounds

Cephalosporin,one ofβ-lactam antibiotics,is favored by many patients and doctors because of its good antibacterial activity,broad antibacterial spectrum,high stability to theβ-lactam enzyme,low tolerant ratio,rare adverse drug reaction and satisfying curative effect,etc,compared with penicillin.The study and exploitation of second substituted cephalosporin hasn't been reported in our country.There hasn't been one of second substituted cephalosporin compounds on the market.It is reported in overseas literature that the series of second substituted cephalosporin compounds can enhance the competence of inhibitingβ-lactam enzyme. So it is supposed that if the second site of cephalosporins mother nuclide is modified,the new compounds would not only retain antibacterial activity and kinetics quality,but also can enhance the competence of inhibitingβ-lactam enzyme.In this paper,a series of cephalosporins compounds are be designed,whose binding competence with penicillin-binding protein(PBP) andβ-lactam enzyme are determined by computer simulation.It shows that second substituted cephalosporins compounds have antibacterial activity and inhibiting enzymatic activity.The study integrates the literature reports and the result of preliminary computer simulation,selects the structure of target compounds,and works out the synthetic mute:GCLE and its derivate,as starting materials,through Mannich condensation,methylation and Michael addition on the product of Mannich condensation,to modify the second site of cephalosporin mother nuclide,obtaining a series of cephalosporin compounds,nine of which are new compounds having not been reported in domestic and overseas literature.The nine new compounds are purified to obtain samples that have good purity.Spectrum analysis methods such as ~1H-NMR are used to ascertain their structure.Their antibacterial activity on Standard Staphylococcus Aureus,Standard Bacillus Canalis Capsulatus and six kinds of clinical drug-resistance bacterium,and stability ofβ-lactam enzyme when they reacted with it are determined.The results show that they have antibacterial activity and two of them which are sulfoxide at first position can inhibitβ-lactam enzyme,compared with cefixime,cefdini and cefazolin,which have been on the market and commonly used in clinic.Thereby,they show the characteristic of going to beβ-lactam enzyme inhibitor.