DSF-inspired discovery of novel zingerone-based quorum-sensing inhibitors: an attractive tactic of fighting Xanthomonas bacterial infections

BACKGROUND Plant bacterial diseases have precipitated a global crisis in human health and food security. In agriculture, diseases such as the rice white-leaf blight can cause considerable reduction in crop yields and, in extreme cases, complete crop failure. Therefore, there is an urgent need for novel green pesticides with innovative modes-of-action (MoAs). RESULTS A series of zingerone derivatives with an isopropanolamine skeleton were designed and their quorum-sensing effects were estimated using biomimetic strategies. The results showed that the novel compound A 12 effectively inhibits the growth of Xanthomonas oryzae pv. oryzae [ Xoo , median effective concentration (EC 50 ) = 3.55 μg mL −1 ], Xanthomonas axonopodis pv. citri ( Xac , EC 50 = 3.23 μg mL −1 ) and Xanthomonas oryzae pv. oryzicola ( Xoc , EC 50 = 7.48 μg mL −1 ). Molecular docking results revealed that A 12 forms multiple interactions with the RpfF protein, while fluorescence titration experiments further verified the interaction between them. Additionally, A 12 was found to effectively inhibit Xoo biofilm formation, extracellular polysaccharide production and other virulence factors. In vivo pot experiments revealed that compound A 12 exhibited excellent curative (53.59%) and protective (57.65%) activity against Xoo . In conclusion, compound A 12 's primary MoA is achieved by affecting the formation of biofilms and the expression of various virulence factors, including related virulence genes. CONCLUSION In summary, this study highlights that compound A 12 displays notable quorum-sensing sensing activity. The advancement of novel quorum-sensing inhibitors through biomimetic strategies offers promising avenues for future research. © 2025 Society of Chemical Industry.