Discovery of novel thiazolidinedione‐benzylpiperidine hybrids as dual‐target antifungal agents for crop disease management

Abstract BACKGROUND Plant fungal diseases, particularly those caused by Rhizoctonia solani , represent a major threat to global food security by causing substantial yield losses. Although chemical fungicides are available, growing pathogen resistance and environmental concerns necessitate the development of novel antifungal agents that are highly effective, eco‐compatible, and operate through distinct mechanisms. RESULTS Twenty‐four benzyl piperidine‐containing thiazolidinedione derivatives were synthesized and their antifungal activities were assessed against six phytopathogenic fungi. In particular, D18 displayed the most potent fungicidal activity against Rhizoctonia solani , with a half‐effective concentration (EC 50 ) of 4.9 μg mL −1 , surpassing that of the control drug azoxystrobin (13.2 μg mL −1 ). In vivo experiments confirmed the high protective and curative efficacy of D18 on rice leaves and sheaths. Furthermore, a series of physiological and biochemical experiments were conducted to investigate the action mechanism exerted by D18 against plant pathogens Rhizoctonia solani . The findings revealed that D18 acted through a novel dual‐action mode: it compromised fungal cell membrane integrity and simultaneously impaired mitochondrial function, resulting in reduced membrane potential, accumulation of reactive oxygen species, and inhibition of succinate dehydrogenase activity. CONCLUSION D18 is a promising antifungal agent with a unique mechanism of action that combines membrane disruption and mitochondrial dysfunction, offering a potential new strategy for sustainable crop protection. © 2026 Society of Chemical Industry.