title: Ligand Promiscuity between the Efflux Pumps Human P-Glycoprotein and S. aureus NorA.
abstract: Thirty-two diverse compounds were evaluated for their ability to inhibit both Pgp-mediated efflux in mouse T-lymphoma L5178 MDR1 and NorA-mediated efflux in S. aureus SA-1199B. Only four compounds were strong inhibitors of both efflux pumps. Three compounds were found to inhibit Pgp exclusively and strongly, while seven compounds inhibited only NorA. These results demonstrate that Pgp and NorA inhibitors do not necessarily overlap, opening the way to safer therapeutic use of effective NorA inhibitors.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Perugia, and Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia , 06123 Perugia, Italy.
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Brincat
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Perugia, and Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia , 06123 Perugia, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Broccatelli
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Perugia, and Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia , 06123 Perugia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Sabatini
authors.affiliation: Department of Neuroscience, Pharmacology Unit, University of Siena , Siena, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Frosini
authors.affiliation: Department of Neuroscience, Pharmacology Unit, University of Siena , Siena, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Neri
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, School of Medicine, Wayne State University and the John D. Dingell Department of Veterans Affairs Medical Center , Detroit, Michigan 48201, United States.
authors.forename: Glenn W
authors.initials: GW
authors.lastname: Kaatz
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Perugia, and Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia , 06123 Perugia, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Cruciani
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Perugia, and Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia , 06123 Perugia, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Carosati
keywords: Multiple drug resistance; NorA; P-glycoprotein; S. aureus; efflux pump inhibitor; promiscuous activity