Synthesis And Biological Activity Of Novel Pyridopyrimidine-containing Dithioacetal Mesoionic Compound

To create candidate agents against bacterial diseases in rice,the dithioacetal structure was introduced into mesoionic compounds to design and synthesize pyrido[1,2-a]pyrimidinone derivatives incorporating dithioacetal moiety in this study.The antibacterial activity in vitro of target compounds against Xanthomonas oryzae pv.oryzae and Xanthomonas oryzae pv.oryzicola was tested.Based on the EC₅₀values,the 3D-QSAR model was established to guide the optimization of the compound structure,and the compound A32 with higher activity was synthesized.The experiments of in vivo antibacterial activity were carried out on the compound A32,and the mechanism of action was preliminarily studied through defense enzyme activity experiments and proteomic techniques.The experimental content and summary were as follows:1.Thirty-one pyrido[1,2-a]pyrimidinone compounds incorporating dithioacetal moiety were designed and synthesized,and characterized by NMR and HRMS.2.The in vitro antibacterial activity of the target compounds against Xoo and Xoc was tested by using the turbidimetric method,and the bioactivity test showed that the EC₅₀values of compound A23 for Xoo and Xoc were 20.1 mg/L and 31.9 mg/L which were superior to the commercial drugs thiodiazole copper（64.8 mg/L and 78.1 mg/L）and bismerthiazol（29.3mg/L and 39.8 mg/L）.The 3D-QSAR model was established based on its EC₅₀values,and the compound A32 with higher activity was designed and synthesized according to the model,with its EC₅₀values of 10.9 mg/L and 17.5 mg/L against Xoo and Xoc.3.The effect of compound A32 on the bacterial surface morphology was observed by SEM,and the fold and depression of the bacterial surface were gradually severe as the concentration of compound increased.4.The experiment of in vivo antibacterial activity against BLB and BLS revealed that the protective activity of compound A32 was 42.67%and 43.92%,which was better than thiodazole copper（40.62%and 35.00%）.5.The preliminary mechanism study was based on the protective activity of compound A32 against BLB.The protective activity of compound A32 has important effects on the increased activity of rice defense enzymes and the upregulated proteins involved in the oxidative phosphorylation pathway.