1. Academic Validation
  2. Design, Synthesis, and Biological Evaluation of Novel Camphor-Based Hydrazide and Sulfonamide Derivatives as Laccase Inhibitors against Plant Pathogenic Fungi/Oomycetes

Design, Synthesis, and Biological Evaluation of Novel Camphor-Based Hydrazide and Sulfonamide Derivatives as Laccase Inhibitors against Plant Pathogenic Fungi/Oomycetes

  • J Agric Food Chem. 2023 Oct 4;71(39):14151-14163. doi: 10.1021/acs.jafc.3c02966.
Zihui Yang 1 Xuebao Sun 1 Yigui Qiu 1 Daojun Jin 1 Yiming Zheng 1 Jia Li 2 Wen Gu 1
Affiliations

Affiliations

  • 1 Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Jiangsu Provincial Key Lab for the Chemistry and Utilization of Agro-forest Biomass, Jiangsu Key Lab of Biomass-Based Green Fuels and Chemicals, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China.
  • 2 School of Foreign Languages, Nanjing Xiaozhuang University, Nanjing 211171, China.
Abstract

To discover novel natural product-based fungicidal agrochemicals, 41 novel camphanic acid hydrazide and camphor sulfonamide derivatives were designed, synthesized, and tested for their Antifungal profile against four plant pathogenic fungi and three oomycetes. As a result, some derivatives presented pronounced inhibitory activities toward Botryosphaeria dothidea, Fusarium graminearum, Phytophthora capsici, and Phytophthora nicotianae. Especially, compound 4b demonstrated the most potent anti-B. dothidea activity (EC50 = 1.28 mg/L), much stronger than positive control chlorthalonil. The in vivo assay showed that 4b displayed significant protective and curative effects on apple fruits infected by B. dothidea. The primary Antifungal mechanism study revealed that 4b could obviously enhance the cell membrane permeability, destroy the mycelial surface morphology and the cell ultrastructure, and reduce the ergosterol and exopolysaccharide contents of B. dothidea. Further, 4b showed potent laccase inhibitory activity in vitro with an IC50 value of 11.3 μM, superior to positive control cysteine. The molecular docking study revealed that 4b could DOCK well into the active site of laccase by forming multiple interactions with the key residues in the pocket. The acute oral toxicity test in rats presented that 4b had slight toxicity with an LD50 value of 849.1 mg/kg bw (95% confidence limit: 403.9-1785.3 mg/kg bw). This research identified that the camphanic acid hydrazide derivatives could be promising leads for the development of novel laccase-targeting fungicides.

Keywords

antifungal/antioomycete activity; camphor; hydrazide; laccase inhibitor; sulfonamide.

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