Document Report Card

ID: ALA1649083

Journal: J Med Chem

Title: Discovery of novel inhibitors of the NorA multidrug transporter of Staphylococcus aureus.

Authors: Brincat JP, Carosati E, Sabatini S, Manfroni G, Fravolini A, Raygada JL, Patel D, Kaatz GW, Cruciani G.

Abstract: 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.

CiteXplore: 21141825

DOI: 10.1021/jm1011963