Design, synthesis, and antifungal activity of novel pogostone-based derivatives containing amide active moieties

Phytopathogenic fungi cause substantial yield losses in various crops. Although traditional chemical fungicides remain effective, adverse effects have become increasingly apparent. The development of fungicides guided by natural products can alleviate these negative impacts to a certain extent.

A series of novel amide-containing pogostone derivatives were prepared and evaluated for their inhibitory activities against 13 pathogenic fungi. Compound 3a₄₇ (N-(2-bromobenzyl)-5-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-5-oxopentanamide) exhibited exceptional efficacy against Valsa mali, with an median effect concentration (EC₅₀) value of 0.95 μg mL^-1. At 200 μg mL^-1, its therapeutic effects on apple branches and fruits (80.81% and 76.87%, respectively) were slightly superior to those of the positive control carbendazim (75.73% and 72.09%). Preliminary mechanistic studies revealed that 3a₄₇ elevated intracellular reactive oxygen species levels, disrupted mitochondrial function and cellular integrity, and ultimately inhibited mycelial growth, leading to apoptosis.

Through systematic bioactivity evaluation, the highly active compound 3a₄₇ was identified. This not only facilitates the screening of candidate compounds for eco-friendly and highly effective fungicides, but also provides guidance and novel strategies for the derivatization and synthesis of pogostone. © 2025 Society of Chemical Industry.