Discovery of Novel Indole Derivatives Containing Imidazolidinone as Potential Antifungal Agents with Mechanistic Studies
Hongqian Zou, Yuhong Wang, Haotao Pu, Hong Fu, Ziye Cheng, Fang Tian, Lijun Gu, Wei Xue
Abstract
A series of indole derivatives containing imidazolidinone were designed and synthesized using natural indole as the starting material. The in vitro antifungal activities of these compounds were evaluated against 11 fungal pathogens. Z25 exhibited the strongest inhibition against Phomopsis sp . ( Ps ), with an EC 50 value of 4.5 μ g/mL, significantly superior to azoxystrobin (38.0 μ g/mL) and fluopyram (77.7 μ g/mL). In vivo antifungal tests on kiwifruit demonstrated that Z25 at 200 μ g/mL provided both curative (71.0%) and protective (82.8%) activities against soft rot, exceeding azoxystrobin. Microscopic observations revealed that Z25 induced hyphal deformation and damage. Further studies indicated that it disrupted cell walls and membranes integrity, resulting in electrolyte leakage, MDA accumulation, and apoptosis. Molecular docking and SDH assays suggested that the antifungal mechanism involves the inhibition of mitochondrial enzymes, highlighting Z25 ’s potential as a naturally derived fungicide.