Design, Synthesis, Antibacterial Activity And Mechanism Of Novel Triazolothiadiazole Sulfones

To discover effective agents that can be used to control rice bacterial diseases,we designed and prepared a series of 6-sulfonyl-1,2,4-triazolo[3,4-b][1,2,4]thiadiazoles using the union of active group.The antibacterial activities against Xanthomonas oryzae pv.oryzae(Xoo)and Xanthomonas oryzae pv.oryzicola(Xoc)of target compounds were evaluated using turbidimetric assays.3D-QSAR models were then developed based on the antibacterial activities and higher activities compounds were prepared according to the models.The highest activities compound in this series compounds were used to test in vivo antibacterial activities against both two rice-pathogenic bacteria.Preliminary mechanism of action studies was carried out using proteomics techniques based on the protective activity against Xoc.The work is summarized as follows.1.Thirty-three 6-sulfonyl-1,2,4-triazolo[3,4-b][1,2,4]thiadiazoles compounds were synthesized,and characterized by ¹H and ¹³C nuclear magnetic resonance,HRMS,and X-ray single-crystal diffraction.2.All compounds showed good antibacterial activities against both two pathogens,with antibacterial EC₅₀ values of 0.59-7.14 mg/L against Xoo,which were significantly better than the commercial agents thiodiazole copper(90.43 mg/L)and bismerthiazol(68.37 mg/L).The antibacterial EC₅₀ values of target compounds were 1.58-14.20 mg/L against Xoc,which were significantly better than the commercial agents thiodiazole copper(97.34 mg/L)and bismerthiazol(75.79 mg/L).The 3D-QSAR models were developed with antimicrobial activities.High antibacterial activities compound V33was synthesized based on the model,which showed EC₅₀ values of 0.59 mg/L and 1.63mg/L against Xoo and Xoc,respectively.3.The cell structure of two pathogens bacteria were observed by SEM.It could be found that the surfaces of both rice pathogenic bacteria appeared wrinkled,dried out,and even ruptured with increasing concentrations of compound V33.4.The results of the pot experiment of compound V33 showed that its protective activity(49.42%)and curative activity(47.94%)against rice leaf blight were superior to those of bismerthiazol(40.09%and 43.71%)and thiodiazole copper(41.51%and37.97%).Protective activity(49.65%)and curative activity(40.67%)against rice bacterial streak of V33 were also better than bismerthiazol(38.89%and 36.25%)and thiodiazole copper(44.28%and 28.20%).5.Preliminary mechanism of action study based on the protective activity of compound V33 against bacterial streak disease showed that the defense enzymes activities and chlorophyll content of rice were significantly increased and photosynthesis-related protein expression was up-regulated after treated with compound V33.This result indicated that V33 might enhance the defense abilities of rice in response to the pathogenic bacteria invasion,reduce oxidative damage by regulated the content of reactive oxygen species in the plant,and enhance the energy conversion in photosynthesis to enhance the disease resistance of rice.