LAUSR

BACKGROUND To explore more potential natural product-based antifungal agents, a series of novel nopol-based carboxamide and hydrazide derivatives containing natural pinene structure was designed, synthesized, and evaluated for their inhibitory activities against seven phytopathogenic fungi and oomycetes. RESULTS The bioassay results indicated that some compounds exhibited good inhibitory activities against Gibberella zeae, Sclerotinia sclerotiorum, and Phytophthora capsici. Among them, compound 3h displayed excellent in vitro activities against G. zeae, with EC50 values of 1.09 mg/L, which was comparable to commercial fungicides bixafen and carbendazim (EC50 = 1.21 and 0.89 mg/L, respectively). Notably, in vivo bioassay results suggested that compound 3h also showed prominent protective and curative effects (95.6% and 94.2%) at 200 mg/L against G. zeae. The SEM study indicated that compound 3h could destroy the morphological integrity of G. zeae hyphae. The in vitro enzyme inhibitory bioassay revealed that compound 3h exhibited potent inhibitory activity against laccase with IC50 values of 4.93 μM, superior to positive control cysteine (IC50 = 35.50 μM), and its binding modes with laccase were elucidated by molecular docking study. In addition, the fluorescent imaging of the dansylamide-labeled derivatives 8 on wheat leaf epidermal cells and the hyphae of G. zeae revealed that this class of hydrazide derivatives could readily permeate into wheat leaves and reached the laccase target in fungal cells. CONCLUSION Some nopol-based hydrazide derivatives exhibited excellent anti-G. zeae activity and laccase inhibitory activity, which merits further development as a new fungicide candidate for controlling Fusarium head blight. This article is protected by copyright. All rights reserved.