Design, synthesis, and antifungal activity of anethole-based oxime ester compounds as potential laccase inhibitors

The improper application of traditional fungicides frequently results in issues such as low fungicide utilization efficiency and environmental contamination. The advent of nanopesticides derived from natural products provides a more promising solution for the green management of agricultural diseases.

In this study, laccase was selected as the biological target, and 24 novel anethole-based oxime ester compounds were rationally designed and synthesized. The chemical structures of these target compounds were systematically validated using Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H NMR) spectroscopy, carbon-13 nuclear magnetic resonance (¹³C NMR) spectroscopy, and high-resolution mass spectrometry (HRMS). In vitro antifungal activity screening was performed against eight plant pathogenic fungi via the agar dilution method, and the results demonstrated that compound 4w exhibited potent antifungal activity against Physalospora piricola. Action mechanism analyses revealed that compound 4w possessed distinct chelating properties, and its interaction mode with laccase suggested that its antifungal activity was likely mediated by targeting laccase. Furthermore, to enhance the application potential of compound 4w, several drug-loaded complexes (4w/CS, 4w/AMCS-1, 4w/AMCS-2, 4w/AMCS-3, and 4w/AMCS-4) were fabricated, and their drug-loaded capacity, microstructure, and sustained releasing performance were investigated.

The target compound 4w may exert potent antifungal activity via laccase inhibition, thereby holding significant potential as a lead compound for the development of the novel green fungicide. Concurrently, the 4w/AMCS-3 complex exhibited promise as a nanopesticide candidate, warranting further investigation. © 2026 Society of Chemical Industry.