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

Abstract

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.

Design, Synthesis, and Fungicidal Activity against Rice Sheath Blight of Novel N-Acyl-1,2,3,4-tetrahydroquinoline Derivatives

“…The in vitro fungicidal activities of all target compounds against five economically important phytopathogenic fungi were conducted based on the previously reported mycelium linear growth rate method . The in vitro bioassays, as listed in Table , indicated that at 40 mg/L, a few compounds exhibited good fungicidal activity against R.…”

“…The in vitro fungicidal activities of all target compounds against five economically important phytopathogenic fungi were conducted based on the previously reported mycelium linear growth rate method. 15 The in vitro bioassays, as listed in Table 1, indicated that at 40 mg/L, a few compounds exhibited good fungicidal activity against R. solani, B. cinerea, P. capsica, and F. graminearum and over one-third of these compounds exhibited moderate to considerable fungicidal activity against R. solani and B. cinerea, which were much higher than that of the natural product, aspernigerin. In particular, compounds 1h, 2b, 2i, 3j, and 3m exhibited excellent activities against R. solani, and 1h, 2i, and 3j exhibited excellent activities against B. cinerea with more than 80% inhibition.…”

“…The structural optimization of the target compounds, preprocessing of the protein structure, and molecular docking procedure were performed using the Molecular Operating Environment drug-discovery-modeling software (MOE 2019.01) . The docking method was based on the method described in our previously published paper . After molecular docking, the best binding mode was selected based on the docking energy results.…”

Synthesis and Antifungal Activity of Novel L‐Menthol Hydrazide Derivatives as Potential Laccase Inhibitors

“…Plant pathogenic fungi can cause a variety of plant diseases, which have been a major threat to crop production. [1] The pathogens plunder a large amount of nutrients and seriously hinder the normal growth of host plants, imposing a great destructive effect on the production of various crops. [2,3] Apple ring rot is a serious disease of apple trees caused by the infection of Botryosphaeria dothidea, which mainly infect apple branches and fruits, resulting in the ring-shaped rots on apple fruits as well as the warts and ulcers on stem epidermis.…”

“…The anti-laccase assay results showed that the active compounds were excellent laccase inhibitors. [14][15][16] Maniak et al synthesized a series of new phenolic hydrazide-hydrazones. The laccase inhibitory assay results and the docking study suggested that the target compounds could be potential laccase inhibitors.…”