Xu Huan, Li Yingchen, Cao Xiaoyan, He Qi, Jin Binyan, Dai Lingjie, Zhang Xinyuan, Zhang Xiaoming, Bian Qiang, Yang Qing, Zhang Li
Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China.
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.
J Agric Food Chem. 2025 Apr 16;73(15):8886-8896. doi: 10.1021/acs.jafc.5c00847. Epub 2025 Apr 2.
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 and as potent inhibitors against f. sp. CDA (CDA). Further bioassays demonstrated that exhibited a protective effect of 61.2% against rice blast at 100 μg/mL, while 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 Zn ion and residues His207 and Tyr152 of CDA are critical for the binding of or , with electrostatic interactions contributing most significantly to the binding free energy. Finally, toxicity predictions confirmed the potential biosafety of and . Overall, this study identified two promising lead compounds targeting fungal CDA to control plant diseases.
真菌几丁质脱乙酰酶（CDA）在病原体与植物的相互作用中起着关键作用，被视为一种创新且有前景的杀菌剂作用靶标。在本研究中，采用了基于药效团的虚拟筛选策略来鉴定化合物 和 作为针对 f. sp. CDA（CDA）的有效抑制剂。进一步的生物测定表明， 在100 μg/mL时对稻瘟病表现出61.2%的保护作用，而 在5 μg/mL时对玉米锈病表现出45.5%的优异保护作用，两者均优于已报道的CDA抑制剂苯并异羟肟酸（BHA）。分子动力学模拟表明，涉及CDA的锌离子以及His207和Tyr152残基的多个关键相互作用对于 或 的结合至关重要，其中静电相互作用对结合自由能的贡献最为显著。最后，毒性预测证实了 和 的潜在生物安全性。总体而言，本研究鉴定出两种有前景的先导化合物，靶向真菌CDA以防治植物病害。
