Discovery of succinate dehydrogenase candidate fungicides via lead optimization for effective resistance management of Fusarium oxysporum f. sp. capsici

Fusarium wilt of chili caused by the fungus Fusarium oxysporum f. sp. capsici (FCO) severely reduces the production of chili worldwide. There is growing evidence of resistance to commercial fungicides targeting succinate dehydrogenase (Sdh) of FCO soliciting the development of new Sdh inhibitors (SdhIs). In the current work, optimized docking and virtual screening were used to mine twelve SdhIs from the ZINC database, followed by in vitro antifungal evaluation on spore and radial mycelium development. Four new promising SdhIs exhibiting a mean mycelium inhibition rate greater than 85.6% (F = 155.8, P = 0.001, P < 0.05) were observed on ten strains of virulent and resistant FCO. Importantly, three of the discovered molecules exhibited potent spore germination inhibition (≥ 80%, P = 0.01, P < 0.05) compared to the commonly used fungicide penthiopyrad. A significant positive correlation (r* ≥ 0.67, P < 0.05) between the activities of the newly discovered SdhIs compared to penthiopyrad against all tested FCO strains indicated a broad-spectrum fungicidal activity. The current findings indicate that the four SdhI’s discovered could judiciously replace certain commercial SdhIs that some FCO displays resistance to.