Structural Simplification of Berberine to Obtain Novel Antifungal Isoquinoline Derivatives against Phytopathogenic Fungi.

Inspired by the natural isoquinoline alkaloid berberine, 57 novel isoquinoline derivatives were designed and synthesized by simplifying its structure and evaluated for their fungicidal activities against plant phytopathogenic fungi. The results showed that most of the 3-phenylisoquinoline derivatives exhibited significant activity against Rhizoctonia solani in vitro. Surprisingly, compounds YKL-41, YKL-42, YKL-46, and YKL-47 substituted by aromatic heterocycles showed a broader antifungal effect compared to berberine, with >60% inhibition at 50 μg/mL. Among them, compound YKL-46 had the best antifungal activity against R. solani with an EC50 value of 5.6 μg/mL. The preliminary mechanism study showed that compound YKL-46 could alter cell membrane permeability, increase the level of reactive oxygen species, and disrupt the normal morphology of mycelium and cells. In vivo experiments showed that compound YKL-46 exhibited some in vivo antifungal activity against rice diseases caused by R. solani at a concentration of 400 μg/mL. Its protective effect (86.2%) was stronger than that of the positive control thiophanate-methyl, and its curative effect (50.3%) was weaker than that of the positive control. This suggests that YKL-46 may be a potential candidate for the treatment of plant fungal diseases that are worth further research.