Structural Simplificationof Luotonin F: Discoveryof Quinoline Derivatives as Novel Antifungal Agents for Plant Protection

Inspired by the natural quinoline alkaloid Luotonin F, a series of quinoline-3-hydrazide derivatives were designed and synthesized by structure simplification and evaluated for their fungicidal activities against plant phytopathogenic fungi. The bioassay results showed that these compounds exhibited broad-spectrum and highly efficient antifungal activities <i>in vitro</i>. Among them, compound <b>W9</b> exhibited broad-spectrum inhibitory activities against R. solani, S. sclerotiorum, B. cinerea, F. graminearum, F. oxysporum, and P. capsici with EC₅₀ values of 0.471, 0.752, 0.570, 0.329, 0.960, and 0.504 μg/mL, respectively. In particular, compound <b>W9</b> was more effective against B. cinerea than the reference drugs Pyrimethanil (EC₅₀ = 3.54 μg/mL) and Boscalid (EC₅₀ = 1.37 μg/mL). Therefore, the preliminary mechanism of action of compound <b>W9</b> on B. cinerea was explored. The results showed that it could affect the mycelial morphology, disrupt the integrity of the cell membrane, and increase the reactive oxygen species content. Furthermore, compound <b>W9</b> exhibited excellent <i>in vivo</i> protection efficacy against B. cinerea compared to the reference drug Pyrimethanil. Thus, compound <b>W9</b> is expected to be a novel broad-spectrum fungicidal candidate, exhibiting excellent fungicidal activities, which is worthy of further investigation.