New inhibitors of chorismate synthase present antifungal activity against .

A structural model of chorismate synthase (CS) from the pathogenic fungus was used for virtual screening simulations. Docking, molecular dynamics, cell growth inhibition and protein binding assays were used for search and validation. Two molecules termed CS8 and CaCS02 were identified. Further studies of the minimal inhibitory concentration demonstrated fungicidal activity against with a minimal inhibitory concentration and minimal fungicidal concentration of 512 and 32 μg·ml for CS8 and CaCS02, respectively. In addition, CaCS02 showed a strong synergistic effect in combination with amphotericin B without cytotoxic effects. studies using recombinant CS from showed IC of 29 μM for CaCS02 supporting our interpretation that inhibition of CS causes the observed fungicidal activity.