From rational design to mechanistic insight: A benzamide-based FtsZ inhibitor as a novel antibacterial agent against Xanthomonas oryzae pv. oryzae

Plant diseases inflict significant economic losses on agriculture and pose a serious threat to global food security, highlighting the urgent need for novel Antibacterial agents. Herein, structure-based rational design strategy was employed to synthesize 23 benzamide derivatives targeting the cell division protein FtsZ from Xanthomonas oryzae pv. oryzae (XooFtsZ). Antibacterial bioassays revealed that compound 19b exhibited potent activity against Xoo with a MIC value of 2.0 μg/mL, representing a 16-fold increase in potency over the commercial bactericides bismerthiazol and thiodiazole copper. At 200 μg/mL, 19b achieved 72.1% in vivo control efficacy against rice Bacterial blight, significantly outperforming both reference agents without causing obvious phytotoxicity to rice Plants. Transmission electron microscopy (TEM) showed that 19b induced marked cellular elongation in Xoo, providing direct morphological evidence of cell division inhibition. Furthermore, molecular studies identified the key binding residues of XooFtsZ that mediate the interaction with 19b.