Discovery of Novel Inhibitors Targeting Fungal Chitin Deacetylase via Virtual Screening for Plant Disease Control
- J Agric Food Chem. 2025 Apr 16;73(15):8886-8896. doi: 10.1021/acs.jafc.5c00847.
- 1. Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China.
- 2. State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection and Shenzhen Agricultural Genome Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
- 3. National Pesticide Engineering Research Center (Tianjin), College of Chemistry, Nankai University, Tianjin 300071, China.
Fungal chitin deacetylase (CDA) plays a crucial role in pathogen-plant interactions, which is regarded as an innovative and promising target for fungicides. In this study, a pharmacophore-based virtual screening strategy was employed to identify compounds VS-24 and VS-25 as potent inhibitors against Puccinia striiformis f. sp. tritici CDA (PstCDA). Further bioassays demonstrated that VS-24 exhibited a protective effect of 61.2% against rice blast at 100 μg/mL, while VS-25 showed a superior protective effect of 45.5% against corn rust at 5 μg/mL, both superior to the reported CDA inhibitor benzohydroxamic acid (BHA). Molecular dynamics simulations revealed that multiple key interactions involving the Zn2+ ion and residues His207 and Tyr152 of PstCDA are critical for the binding of VS-24 or VS-25, with electrostatic interactions contributing most significantly to the binding free energy. Finally, toxicity predictions confirmed the potential biosafety of VS-24 and VS-25. Overall, this study identified two promising lead compounds targeting Fungal CDA to control plant diseases.