Citral‐based amide derivatives improve the antifungal activity of Kresoxim‐methyl against Rhizoctonia solani

Abstract BACKGROUND Rhizoctonia solani , the fungal pathogen causing rice sheath blight, threatens global food security. Prolonged use of Kresoxim‐methyl (KM), a common fungicide, has led to resistance and reduced effectiveness. This study investigates the synergistic effects of citral‐based amide derivatives with KM and explains the underlying mechanisms. RESULT Among the tested derivatives, compound d25 exhibited the most pronounced synergistic effect, achieving a peak synergistic ratio (SR = 2.66 ± 0.67) at a molar ratio of 25% in the mixture. At a molar ratio of 10%, the mixture (Mix) demonstrated significant antifungal activity both in vitro and in vivo , effectively reducing mycelial dry weight and enhancing rice leaf protection. Mechanistic studies revealed that Mix disrupted the tricarboxylic acid (TCA) cycle, thereby inhibiting energy metabolism. Additionally, d25 interfered with arachidonic acid metabolism, impairing cell membrane repair mechanisms and enhancing the fungicidal efficacy of KM. Toxicity assessments revealed that d25 exhibited minimal cytotoxicity against human cell lines and low acute toxicity toward Apis mellifera L. and zebrafish. CONCLUSION The findings elucidate the synergistic mechanisms of d25 and Mix, underscoring their potential as effective fungicide synergists. This study establishes a robust theoretical and practical foundation for enhancing the efficacy of chemical control strategies against R. solani , providing new insights into the development of safe and efficient fungicide formulations. © 2025 Society of Chemical Industry.