Design, Synthesis And Antibacterial Activity Of Novel Diaryl Ether Derivatives Containing Isopropanolamine Substructur

Controlling bacterial infections in plants is a major challenge due to the appearance of resistant strains.As a physical barrier,the bacterial biofilm helps bacterial infections acquire drug resistance by enabling bacteria to accommodate complex and volatile environmental conditions and avoid bactericides’effects.Thus,developing new antibacterial agents with antibiofilm potency is imperative.In this paper,a series of diaryl ether derivatives containing isopropanolamine substructure were designed and synthesized,and the in vitro antibacterial activity against three plant pathogens was tested by turbidity method.The bismerthiazol（BT）and thiediazole copper（TC）were used as control agents.Among them,compound C₈ showed excellent activity against Xanthomonas oryzae pv.oryzae（Xoo）and Xanthomonas axonopodis pv.citri（Xac）with EC₅₀ values of 0.34 and 2.11μg/mL,respectively.In addition,compound A₄ showed best activity against Pseudomonas syringae pv.actinidiae（Psa）with EC₅₀ value 2.63μg/mL,these two compounds’activities were considerably better than BT and TC.The in vitro antifungal activity of the target molecules against the Verticillium dahlia（V.d.）,Sclerotinia sclerotiorum（S.s.）,Gibberella zeae（G.z.）,Rhizoctonia solani Kühn（R.s.）,Fusarium oxysporum（F.o.）,and Botryosphaeria dothidea（B.d.）were evaluated by mycelia growth inhibition experiments,while the carbendazim（CB）was served as a reference drug.Among them,compound B₁₇ exerted the best antifungal activity against V.d.(EC₅₀=22.69μg/mL)and compound A₆ exerted the best antifungal activity against S.s.(EC₅₀=20.01μg/mL).In vivo trials revealed that compound C₈ exhibited excellent protective activities against rice bacterial blight and citrus bacterial canker at 200μg/mL,with a control effectiveness of 49.57%and 85.60%,respectively;compound A₄ demonstrated outstanding protective activity with a value of 77.23%against Psa.In addition,the optimal target compound C₈ was selected for the preliminary mechanism exploration of Xoo.Sub-inhibitory concentration of compound C₈ could inhibit biofilm formation and EPS production,which was verified by SEM.Furthermore,a swimming motility inhibition assay and pathogenicity assay showed that compound C₈ causes decreased swimming motility and pathogenicity of Xoo;compound C₈ inhibited the production of DSF signaling molecules.The RT-qPCR assays illustrated that compound C₈ inhibits biofilm formation by suppressing the expression of virulence factor–related genes.