Triazole Sulfonamide\nDerivates: Inhibitors of the <i>bc</i><sub>1</sub> Complex\nto Control Cucumber Downy Mildew

Cucumber downy mildew (CDM), caused by Pseudoperonospora\ncubensis, is a destructive disease that affects greenhouse\ncucumbers and causes significant losses for growers. Amisulbrom, a\ntriazole sulfonamide fungicide targeting the Qi site in the <i>bc</i><sub>1</sub> complex, has shown potential in effectively\ncombating CDM. However, its detailed binding mode with the target\nis unclear. In this study, a three-dimensional (3D) structure of the <i>bc</i><sub>1</sub> complex from P. cubensis was built, and its interaction with amisulbrom was investigated\nby integrating molecular docking, molecular dynamics, and molecular\nmechanics/Poisson−Boltzmann surface area (MM/PBSA) methods.\nBased on the binding mode of amisulbrom with the Pc-<i>bc</i><sub>1</sub> complex, a scaffold hopping strategy was performed,\nand compounds <b>11a</b>–<b>o</b> and <b>12a</b>–<b>v</b> were designed. Among them, compound <b>12g</b> showed excellent fungicidal properties against CDM in\nfield trials. The present work indicated that the oxime ether moiety\ncould be further optimized for better results. Furthermore, compound <b>12g</b> has the potential to serve as a lead compound in the search\nfor new Qi-site inhibitors of the <i>bc</i><sub>1</sub> complex.