Design, Synthesis, and Biological Activity of Novel Laccase Inhibitors as Fungicides against Rice Blast

Laccase is a potential target for novel agricultural fungicide discovery. PMDD-5Y was the first agent reported with high activity against laccase to control phytopathogenic fungi. Thirty-two novel agents containing cinnamaldehyde thiosemicarbazide were synthesized with PMDD-5Y as the lead compound, with most of the target compounds exhibiting excellent activity in vitro. Compound a2 (EC₅₀ = 9.71 μg/mL) exhibited greater potency against Magnaporthe oryzae than the commercial fungicide isoprothiolane (EC₅₀ = 18.62 μg/mL). The curative and protective effects of a2 against M. oryzae on rice were more than those of PMDD-5Y. Scanning electron microscopy indicated that a2 could cause mycelial growth atrophy and malformation. Furthermore, a2 (IC₅₀ = 0.18 mmol/L) showed higher activity against laccase than PMDD-5Y (IC₅₀ = 0.33 mmol/L) and cysteine (IC₅₀ = 0.30 mmol/L). Molecular docking analysis revealed the nature of interaction between these compounds and laccase. This research identified a novel laccase inhibitor a2 as a fungicide candidate to control rice blast in agriculture.