Discovery of novel inhibitors of the NorA multidrug transporter of Staphylococcus aureus

Four novel inhibitors of the NorA efflux pump of Staphylococcus aureus, discovered through a virtual screening process, are reported The four compounds belong to different chemical classes and were tested for their in vitro ability to block the efflux of a well-known NorA substrate, as well as for their ability to potentiate the effect of ciprofloxacin (CPX) on several strains of S aureus, including a NorA overexpressing strain Additionally, the MIC values of each of the compounds individually are reported A structure-activity relationship study was also performed on these novel chemotypes, revealing three new compounds that are also potent NorA inhibitors The virtual screening procedure employed FLAP, a new methodology based on GRID force field descriptors