Design, Synthesis, and Biological Evaluation of Novel Quinoline Derivatives Containing 1,3,4-Oxadiazole Moieties as Potential Antifungal Agents

To discover novel green antifungal candidates, herein, a series of 8-hydroxyquinaldine derivatives were designed and synthesized by introducing the antifungal fragment 1,3,4-oxadiazole. Their antifungal activities against phytopathogenic fungi were evaluated to develop quinoline-based antifungal agents. The results showed that compound <b>VIa6</b> displayed better <i>in vitro</i> antifungal activity against <i>Valsa mali</i> with an EC₅₀ value of 0.091 μmol/mL. Significantly, compound <b>VIa6</b> displayed superior <i>in vivo</i> preventive and therapeutic effects against <i>V. mali</i>, comparable to that of Chlorothalonil. Moreover, the combination of <b>VIa6</b> and Chlorothalonil showed good synergistic antifungal effects. Additionally, compound <b>VIa6</b> exerted good selectivity and relatively low toxicity to nontarget organisms. Finally, a preliminary antifungal mechanism study indicated that <b>VIa6</b> affected the viability of fungi by inducing intracellular oxidative damage in <i>V. mali</i> and disrupting the integrity of the fungus cell membranes. These findings demonstrated that the novel quinoline derivative <b>VIa6</b> possessed excellent <i>in vitro</i> and <i>in vivo</i> antifungal activity, offering the potential as a novel green agricultural antifungal agent.