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
Discovery of novel inhibitors of the NorA multidrug transporter of Staphylococcus aureus / Brincat, J.P., Carosati, E., Sabatini, S., Manfroni, G., Fravolini, A., Raygada, J.L., Patel, D., Kaatz, G.W., Cruciani, G.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 54:1(2011), pp. 354-365. [10.1021/jm1011963]
Discovery of novel inhibitors of the NorA multidrug transporter of Staphylococcus aureus
Carosati, Emanuele;
2011-01-01
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 descriptorsPubblicazioni consigliate
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