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 in vitro. Among them, compound W9 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 W9 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 W9 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 W9 exhibited excellent in vivo protection efficacy against B. cinerea compared to the reference drug Pyrimethanil. Thus, compound W9 is expected to be a novel broad-spectrum fungicidal candidate, exhibiting excellent fungicidal activities, which is worthy of further investigation.