Design, Synthesis And Antibacterial Activity Of Amide Compounds Containing Glycyrrhetinic Acid And Ursolic Aci

Natural products are important precursor compounds for the development of new pesticides due to their low toxicity,easy degradability,and eco-friendliness.Therefore,in this study,a series of 18β-glycyrrhetinic acid（18β-GA）derivatives and ursolic acid（UA）derivatives containing an amide backbone were designed and synthesized with the natural products 18β-glycyrrhetinic acid and ursolic acid as the precursors,and the target compounds were evaluated for their in vitro and in vivo antibacterial activities.The in vitro antimicrobial activity test showed that compound A₂₂ exhibited excellent antimicrobial activity against rice leaf blight（Xanthomonas oryzae pv.oryzae,Xoo）and citrus ulcer（Xanthomonas axonopodis pv.citri,Xac）with EC₅₀ values of 3.34 mg L^-1 and 3.30 mg L^-1,respectively which were better than those of the commercially available commercial drugs bismerthiazol(BT,anti-Xoo,EC₅₀=28.34 mg L^-1 and anti-Xac,EC₅₀=101.64 mg L^-1)and thiodiazole copper(TC,anti-Xoo,EC₅₀=119.87mg L^-1 and anti-Xac,EC₅₀=86.54 mg L^-1).The results of in vivo antimicrobial activity tests showed that compound A₂₂ at a dose of 200 mg L^-1 reduced leaf blight disease on rice leaves（therapeutic activity:44.74%,protective activity:50.44%）and ulcer disease on citrus leaves（therapeutic activity:58.86%,protective activity:84.37%）.Whereafter,Xoo was selected as the test bacteria for preliminary antibacterial mechanism studies.The results showed that the target molecule A₂₂induced the excessive production and accumulation of reactive oxygen species（ROS）in Xoo cells,leading to a decrease in superoxide dismutase（SOD）and catalase（CAT）enzyme activities and an increase in malondialdehyde（MDA）content.Interestingly,hydrogen peroxide（H₂O₂）plate experiments showed that the addition of exogenous H₂O₂ at low concentrations stimulated the burst of ROS in Xoo cells.In addition,the target molecule A₂₂ increased Xoo cell membrane permeability,which ultimately led to cell death.