Isolating Antipathogenic Fungal Coumarins from Coriaria nepalensis and Determining Their Primary Mechanism In Vitro .

Through bioassay-guided isolation, eight undescribed coumarins ( 1 - 8 ), along with six reported coumarins ( 9 - 14 ), were obtained from Coriaria nepalensis. The new structures were determined by using IR, UV, NMR, HRESIMS, and ECD calculations. The results of the biological activity assays showed that compound 9 exhibited broad spectrum antifungal activities against all tested fungi in vitro and a significant inhibitory effect on Phytophthora nicotianae with an EC 50 value of 3.00 μg/mL. Notably, compound 9 demonstrated greater curative and protective effects against tobacco balack shank than those of osthol in vivo . Thus, 9 was structurally modified to obtain new promising antifungal agents, and the novel derivatives ( 17b , 17j , and 17k ) exhibited better effects on Sclerotinia sclerotiorum than did lead compound 9 . Preliminary mechanistic exploration illustrated that 9 could enhance cell membrane permeability, destroy the morphology and ultrastructure of cells, and reduce the exopolysaccharide content of P. nicotianae mycelia. Furthermore, the cytotoxicity results revealed that compound 9 exhibited relatively low cytotoxicity against HEK293 cell lines with an inhibition rate of 33.54% at 30 μg/mL. This research is promising for the discovery of new fungicides from natural coumarins with satisfactory ecological compatibility.