Design, synthesis, and mechanism study of novel isoquinoline derivatives containing an oxime moiety as antifungal agents.

A series of novel isoquinoline derivatives 5a-5 s incorporating bioactive amide and oxime ester moieties were rationally designed and synthesized based-on isoquinoline alkaloid scaffolds through pharmacophore splicing strategy. Their structures were verified by ¹H NMR, ¹³C NMR, IR and HRMS. The fungicidal bioassay indicated that most of the target compounds showed good to excellent inhibitory activity against five phytopathogenic fungi in vitro at a concentration of 50 mg/L. Notably, compounds 5 l and 5q exhibited excellent fungicidal activity against S. sclerotiorum with EC₅₀ values reached 8.27 and 8.18 mg/L, respectively, which were comparable to boscalid (8.03 mg/L). 5q exhibited 100% protective and 73.87% curative efficacy against S. sclerotiorum on Brassica napus L. leaves at 100 mg/L. Particularly, compound 5q exhibits potent inhibitory effect against Succinate dehydrogenase (SDH) of S. sclerotiorum with IC₅₀ of 5.05 uΜ. Furthermore, SDH activity assays and molecular docking analyses demonstrated that 5q can interact with SDH in a variety of ways. These results provide substantial insight for the development of novel natural-derived isoquinoline derivatives as potential antifungal agents.