Piperidine‐functionalized formononetin derivatives: Design, synthesis and evaluation of antibacterial activity, modes and phenotypes

BACKGROUND Plant pathogenic bacteria severely impact crop yield and quality. Long‐term use of conventional bactericides has led to resistance, and raised environmental and food safety concerns, necessitating new, efficient and eco‐friendly agents. RESULTS This study designed and synthesized a series of novel piperidine‐functionalized formononetin derivatives (N1–N42) and evaluated their antibacterial activity. In vitro assays showed that several compounds strongly inhibited Xanthomonas oryzae pv. oryzae ( Xoo ) and Xanthomonas axonopodis pv. citri ( Xac ). Notably, thiourea‐piperidine N30 and piperidine hydrochloride N42 were highly effective against Xoo , with median effective concentration (EC 50 ) values of 6.5 and 4.0 μg mL −1 , respectively, outperforming the controls thiodiazole copper (TC, 33.3 μg mL −1 ) and zinc thiazole (ZT, 13.9 μg mL −1 ). N42 also exhibited potent activity against Xac (EC 50 = 7.5 μg mL −1 ), superior to activities of TC (30.7 μg mL −1 ) and ZT (58.7 μg mL −1 ). In vivo pot experiments confirmed that N30 exhibited good efficacy against rice bacterial leaf blight ( BLB ), whereas N42 showed dual efficacy in controlling both BLB and citrus canker ( CC ). Further investigation of the antibacterial modes and related phenotypes revealed that N30 and N42 could cause bacterial cell‐envelope damage, decrease biofilm formation and exopolysaccharide (EPS) production, attenuate swarming motility, reduce the activities of extracellular virulence‐related enzymes, and enhance the activities of defense‐related enzymes in host plants. CONCLUSION N30 and N42 have good potential to be developed as formononetin‐based antibacterial agents.