Evolution from Natural -Carboline Alkaloids to Obtain 1,2,4,9-tetrahydro-3-thia-9-aza-fluorene Derivatives as Potent Fungicidal Agents against .

Rice sheath blight, caused by , is a globally important rice disease and the increasing resistance of this pathogen highlights the need for new active compounds against rice sheath blight. In this study, natural -carboline alkaloids were optimized to obtain a series of 1,2,4,9-tetrahydro-3-thia-9-aza-fluorene derivatives and evaluated for their fungicidal activity and mode of action against . Of these compounds, exhibited significant in vitro fungicidal activity against , with an EC value of 2.35 μg/mL, and was more active than validamycin A. In vivo bioassay also demonstrated that displayed superior protective and curative activities as compared to validamycin A. Mechanistically, not only induced the loss of mitochondrial membrane potential and accumulation of reactive oxygen species, but also interfered with DNA synthesis. Therefore, compound displayed pronounced in vitro and in vivo fungicidal activity against and could be used as a potential candidate for the control of rice sheath blight.