Design, Synthesis, and Biological Evaluation of Novel Indole Derivatives with Biphenyl and Diphenyl Ether Moieties as Potential Fungicidal Agents
Xu-Shun Gong, Tian-Yu Zhang, Ya-Ping Liu, Li Zhao, Dan Xu, Huan Zhou, Xili Liu, Gong XuAbstract
Natural products are valuable resources for eco-friendly fungicides. In this study, a series of novel indole derivatives A1–A34 and B1–B7 were designed by incorporating biphenyl and diphenyl ether fragments. In vitro antifungal assays revealed that compound A3 displayed broad-spectrum activity against Sclerotinia sclerotiorum, Valsa mali, Botrytis cinerea, Rhizoctonia solani, Physalospora piricola, and Fusarium graminearum, with EC50 values of 2.60, 0.577, 3.78, 3.71, 2.46, and 5.22 mg/L, respectively. Compound A6 exhibited the highest potency against P. piricola (EC50 = 0.906 mg/L). In vivo experiments on detached branches confirmed the significant protective activity of A3 against V. mali. The in vitro enzymatic assays, molecular docking, and comparative analyses of structural and energy orbitals indicated that compound A3 exhibited superior binding affinity, suggesting its potential as a mitochondrial complex III inhibitor in V. mali. Therefore, compound A3 represents a promising lead for developing novel broad-spectrum indole-based fungicides for crop protection.