Discovery of Novel Indole Derivatives Containing Imidazolidinone as Potential Antifungal Agents with Mechanistic Studies

A series of indole derivatives containing imidazolidinone were designed and synthesized using natural indole as the starting material. The <i>in vitro</i> antifungal activities of these compounds were evaluated against 11 fungal pathogens. <b>Z25</b> exhibited the strongest inhibition against <i>Phomopsis</i> <i>sp</i>. (<i>Ps</i>), with an EC₅₀ value of 4.5 <i>μ</i>g/mL, significantly superior to azoxystrobin (38.0 <i>μ</i>g/mL) and fluopyram (77.7 <i>μ</i>g/mL). <i>In vivo</i> antifungal tests on kiwifruit demonstrated that <b>Z25</b> at 200 <i>μ</i>g/mL provided both curative (71.0%) and protective (82.8%) activities against soft rot, exceeding azoxystrobin. Microscopic observations revealed that <b>Z25</b> 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 <b>Z25</b>'s potential as a naturally derived fungicide.