Study On Synthesis And Antibacterial Activity Of Quinazolinones

Objective:Drug-resistant bacteria emerge in endlessly due to the improper use of antimicrobials. As the drug research object, to find compounds effective to clinical drug resistance bacteria is of great significance.Methods:Firstly, compounds1-29were synthesized according to structure split principle. And compounds3a-t and4a-s were synthesized according to ketene structure sulfur into pyrimidine ketone. All the compounds were synthesized with the conventional synthetic methods, and the hydrogen spectrum and the carbon spectrum structure were adopted to confirm the structure of each compound. Clinical drug susceptibility method was used to screen9kinds of drug-resistant bacteria. The TCC colorimetric method is adopted to screen the activities of all the compounds against multi-drug resistant bacteria.Results:Finally,69compounds were synthesized. After pharmacological activity determination, compounds1-29showed good activity against multi-drug resistance bacteria. And the minimum inhibitory concentration (MIC) was0.5μg/ml for many of the compounds, in which compound3,6and21exhibited equally effective to gram positive and gram negative bacteria, compound14can be against four types of bacteria at the same time. The strains adopted are obtained from clinical patients and after being cultured and verified, by which these compounds that showed good antibacterial activity can reflect the medicinal value for them. The antibacterial effects of many compounds are better than Aaztreonam and Ceftazidime pentahydrate which are the current clinical application drags. However, the activation of Pyrimidine-2-ketone sulfur compounds is worse. The minimal inhibitory concentrations (MIC) in two series of40compounds are all above0.5ug/ml, which may be caused by the poor solubility of compounds.Conclusions:69compounds were obtained through2or3steps and the structures for these compounds are all confirmed by1H-NMR and13C-NMR. The antibacterial activity of many compounds are good by antibacterial activity screening method, especially compound14deserves further research and development.