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

Abstract 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.