Study On Antibacterial Activity And The Structure-activity Relationship Of Oxazolidones

[Backgroud and Objective]Recently, bacterial drug resistance is more and more serious, in order to control the infection of drug-resistance bacteria, study on new antibacterial drug is necessary. Oxaz-olidones can inhibit multidrug resistant of G+ bacteria.Oxazolidones is a group of antibacterial agent deserved to study and have a good application perspective. Based on theoretical study on structure-activity relationships, A serial of Oxazolidones have been synthetized. The objective of thia paper is the study on antibacterial activity and quantitative structure activity relationship, in order to provide theory method for designing new oxazolidinones with stronger activity.[Methods]1.Their antibacterial activity in vitro were evaluated by broth dilution method. We determinined the MIC value.we choose Normo-staphylococcus aureus (CMCC26003) and clinical staphylococcus aureus(drug-resistance bacteria) to value their antibacterial activity.2.Theoretical study on 3D-QSAR has been done using comparative molecular field analysis(CoMFA) and the 2D-QSAR has been done based on the melocular structure descriptor.3.We calculated the melocular structure descriptor of different substituent groups to study whether the molecular descriptor are well-distributed.[Results]1. Among 74 compounds,TY101-11,12,13,17,18,19,20,21,22,24,25,26,27,28,29,30,38,39,43,44,45,46,48,59,62,63,64,66,68,69,73,74 show better antibacterial activity than others,MIC≤4μg/ml.2. TY101-26,29,38,39,48,59,69 show antibacterial activity on clinical drug-resistance Staphylococcus Aureus(MIC≤2～8μg/ml),but no sterilizing activity is observed(MBC>64μg/ml).3. Theoretical study on structure-activity relationships has been done using compara -tive molecular field analysis(CoMFA). The 3D-pharmacophore model of the oxazolidinones was obtained,the cross validation q2=0.111,the non-cross validation R2=0.971, SD(Standard Error of Estimate)=0.072, The model has nopredicting capability,CoMFA Model is not successful,then the 2D-QSAR was done, the correlation coefficient (R2) is 0.12923, the cross-validatded R2 is 0.00203.3. Vsa_pol and vsa_don are not well-distributed.【Conclusion】1.32 of 74 oxazolidones have antibacterial activity on Staphylococcus aureus (MIC≤4μg/ml),TY101 -26,29,38,39,48,59,69 show antibacterial activity on clinical drug-resistance Staphylococcus aureus,but the inhibition activity is inferior to linezolid,they are not deserved to be study.2.74 compounds are not representative and incompetent to construct a QSAR model. Based on study on structure-activity relationship, we conclude:in proceeding of lead optimization,we shoud think over not only possibility of synthesis but also substituent physical parameter and chemistry parameter should variance in enough extend.and the substituent distribution should be adqulis,in this way,the effect on activity could be displayed.