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 EC50 values of 8.420 and 8.414 µg/mL, respectively. Their efficacies were superior to that of widely used commercial fungicides azoxystrobin (AZO, 20.649 µg/mL) and cabendazim (CAB, 251.625 µg/mL). Furthermore, compound 5v exhibited excellent in vitro antifungal activity against Sclerotinia sclerotiorum (S. sclerotiorum), with an EC50 value of 12.829 µg/mL, significantly outperforming AZO (63.629 µg/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 µg/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.