Structural Simplification of Luotonin F: Discovery of 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 <i>R. solani</i>, <i>S. sclerotiorum</i>, <i>B. cinerea</i>, <i>F. graminearum</i>, <i>F. oxysporum</i>, and <i>P. capsici</i> 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 <i>B. cinerea</i> 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 <i>B. cinerea</i> 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 <i>B. cinerea</i> 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.