Abstract
ABSTRACT
To address the challenge of fungicide resistance in plant pathogenic fungi, coumarin derivatives were designed. Two series of coumarin derivatives, including 3‐amide and thienocoumarin ether derivatives, were designed and synthesized through structural modification of the coumarin scaffold to explore their antifungal potential. Their antifungal activities were evaluated using the mycelial growth rate method, with half‐maximal effective concentration (EC
50
) values determined. The effects of compound
IVd
on membrane integrity and morphology were assessed by measuring electrolyte leakage, malondialdehyde (MDA) content, and scanning electron microscopy (SEM). Synergistic effects were quantified using Wadley's method by calculating the synergistic ratio (SR). Molecular docking studies were conducted to investigate interactions with potential targets (CYP51, CYP51B, and SDH). Among the derivatives,
IVd
showed the most potent antifungal activity, with EC
50
values of 88.5 µg/mL against
Valsa mali
, slightly surpassing azoxystrobin (EC
50
= 92.8 µg/mL). Treatment with
IVd
caused membrane disruption and hyphal deformation. A 2:1 combination ratio of
IVd
with azoxystrobin or fluconazole demonstrated synergistic effects (SR > 1.5). Molecular docking suggested favorable interactions with the investigated targets, supporting its multitarget activity. Overall, these findings highlight
IVd
as a promising antifungal scaffold for investigation and provide evidence for its potential use in combination strategies against plant pathogenic fungi.