FM-568: A Promising Phenyl-Hydrazonomalononitrile Antibacterial Agent for the Sustainable Management of Citrus Canker

Citrus canker, caused by Xanthomonas citri subsp. citri (Xcc), poses a significant threat to citrus production worldwide. To develop effective and eco-friendly antibacterial agents, we designed and synthesized phenyl-hydrazonomalononitrile derivatives using a scaffold-hopping strategy. Among these, FM-568 emerged as a potent candidate, exhibiting broad-spectrum antibacterial activity in vitro against various phytopathogenic bacteria, including Xcc. Greenhouse experiments demonstrated that FM-568 achieved a control efficacy of 88.36% against citrus canker at 400 μg/mL, with an EC₅₀ of 26.68 μg/mL. Field trials in two major citrus-producing regions in China confirmed its effectiveness, yielding control efficacies of 86.60 and 77.87% at 400 μg/mL, outperforming conventional agents like zinc thiazole and thiadiazole copper. Density functional theory calculations suggested that FM-568's optimized scaffold and electronic properties contribute to its enhanced antibacterial activity. These findings indicate that FM-568 is a promising eco-friendly alternative for managing citrus canker. Further studies on its mechanism of action, safety profile, and formulation optimization are warranted to advance its development for sustainable citrus production.