Discovery of novel piperidine‐containing thymol derivatives as potent antifungal agents for crop protection

Abstract BACKGROUND Plant fungal diseases pose a significant threat to crop production. The extensive use of chemical pesticides has led to growing environmental safety risks and pesticide resistance of various plant pathogens. Therefore, it is an urgent task to explore novel eco‐friendly fungicidal agents with high efficacy to combat fungal infection. RESULTS In this study, we rationally designed a series of novel thymol derivatives by incorporation of the sulfonamide moiety and evaluated their biological activities against plant pathogenic fungi. The bioassay results underscored the remarkable in vitro antifungal activity of compounds 5m and 5t against Phytophthora capsici ( P. capsici ), with EC 50 values of 8.420 and 8.414 μ g/mL, respectively. Their efficacies were superior to that of widely used commercial fungicides azoxystrobin (AZO, 20.649 μ g/mL) and cabendazim (CAB, 251.625 μ g/mL). Furthermore, compound 5v exhibited excellent in vitro antifungal activity against Sclerotinia sclerotiorum ( S. sclerotiorum ), with an EC 50 value of 12.829 μ g/mL, significantly outperforming AZO (63.629 μ g/mL). In vivo bioassays demonstrated the impactful activity of compound 5v against S. sclerotiorum , achieving over 98% curative and protective efficacies at the concentration of 200 μ g/mL. Further mechanistic investigations unveiled that compound 5v induced mycelial shrinkage and collapse in S. sclerotiorum , resulting in organelle damage and the accumulation of antioxidant enzyme activity. CONCLUSION The significant antifungal efficacy of the prepared thymol derivatives shall encourage further exploration of compound 5v as a promising candidate to develop novel fungicides for crop protection. © 2024 Society of Chemical Industry.