Cinnamic acid–hordenine hybrid derivatives as T3SS inhibitors against Dickeya spp. for soft rot disease control

BACKGROUND: The type III secretion system (T3SS) is a key virulence determinant in Dickeya species and is essential for successful host invasion and symptom development. To identify effective antivirulence agents, a series of novel hybrid molecules was designed and synthesized by linking cinnamic acid with hordenine. These compounds were evaluated for their ability to inhibit the T3SS of Dickeya oryzae EC1 without impairing bacterial growth. RESULTS: A total of 22 hybrid derivatives were synthesized. Among them, compound I-3 significantly reduced the promoter activity of the T3SS gene hrpA without inhibiting the growth of D. oryzae EC1. Mechanistic analyses revealed that compound I-3 effectively suppressed the EC1-triggered hypersensitive response in tobacco, down-regulated the expression of multiple T3SS-related genes, and inhibited the secretion of type III effector proteins. In planta assays further confirmed that compound I-3 attenuated the virulence of D. oryzae EC1 on rice and alleviated the disease symptoms caused by Dickeya dadantii 3937 in potato and Dickeya fangzhongdai CL3 in taro, indicating a broad-spectrum antivirulence activity. CONCLUSION: This study identifies compound I-3 as a promising hybrid molecule that suppresses T3SS activity in D. oryzae EC1 and reduces the virulence of multiple Dickeya species across diverse host plants. These findings provide both a theoretical foundation and practical guidance for the development of novel T3SS-targeting antivirulence agents to control soft rot diseases in crops. © 2026 Society of Chemical Industry.