Synthesis and Fungicidal Activities of Coumarin Derivatives as Succinate Dehydrogenase Inhibitors.

Succinate dehydrogenase inhibitors (SDHIs) have been developed to the fastest growing family of fungicides. To develop novel succinate dehydrogenase (SDH) inhibitors, 27 novel non-amides coumarin derivatives were designed, synthesized, and characterized. The bioassay revealed that most of the target compounds exhibited significant antifungal activity against Botrytis cinerea in vitro. Notably, compounds 1a and 2c with EC values of 0.92 and 0.52 µg/mL, respectively, which were better than that of positive control chlorothalonil (EC = 3.14 µg/mL). Moreover, in vivo antifungal assay results showed that compound 2c could observably inhibit the growth of B. cinerea on Kuerla pears with remarkable protective at a dosage of 200 µg/mL. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) investigation indicated that compound 2c significantly damaged the cell structures of B. cinerea mycelium. Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were analyzed for structure-activity relationships of all target compounds. Furthermore, molecular docking revealed that compound 2c was able to bind closely to the receptor protein of SDH. Enzyme activity analysis also further verified its inhibitory effect. These results demonstrated that compound 2c may be potential candidate for novel SDH inhibitors, and these results afforded further valuable reference for SDHIs discovery.