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

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 VIa6 displayed better in vitro antifungal activity against Valsa mali with an EC₅₀ value of 0.091 μmol/mL. Significantly, compound VIa6 displayed superior in vivo preventive and therapeutic effects against V. mali, comparable to that of Chlorothalonil. Moreover, the combination of VIa6 and Chlorothalonil showed good synergistic antifungal effects. Additionally, compound VIa6 exerted good selectivity and relatively low toxicity to nontarget organisms. Finally, a preliminary antifungal mechanism study indicated that VIa6 affected the viability of fungi by inducing intracellular oxidative damage in V. mali and disrupting the integrity of the fungus cell membranes. These findings demonstrated that the novel quinoline derivative VIa6 possessed excellent in vitro and in vivo antifungal activity, offering the potential as a novel green agricultural antifungal agent.