title: Improved Potency of Indole-Based NorA Efflux Pump Inhibitors: From Serendipity toward Rational Design and Development.
abstract: The NorA efflux pump is a potential drug target for reversal of resistance to selected antibacterial agents, and recently we described indole-based inhibitor candidates. Herein we report a second class of inhibitors derived from them but with significant differences in shape and size. In particular, compounds 13 and 14 are very potent inhibitors in that they demonstrated the lowest IC50values (2 μM) ever observed among all indole-based compounds we have evaluated.
authors.affiliation: Department of Chemistry, Biology and Biotechnology, University of Perugia , 06123 Perugia, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Buonerba
authors.affiliation: Department of Chemistry, Biology and Biotechnology, University of Perugia , 06123 Perugia, Italy.
authors.forename: Susan
authors.identifier: 0000-0003-1024-7368
authors.initials: S
authors.lastname: Lepri
authors.affiliation: Department of Chemistry, Biology and Biotechnology, University of Perugia , 06123 Perugia, Italy.
authors.forename: Laura
authors.identifier: 0000-0002-9282-9013
authors.initials: L
authors.lastname: Goracci
authors.affiliation: The John D. Dingell Department of Veterans Affairs Medical Center , Detroit, Michigan 48201, United States.
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Schindler
authors.affiliation: The John D. Dingell Department of Veterans Affairs Medical Center , Detroit, Michigan 48201, United States.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Seo
authors.affiliation: The John D. Dingell Department of Veterans Affairs Medical Center , Detroit, Michigan 48201, United States.|Department of Internal Medicine, Division of Infectious Diseases, Wayne State University School of Medicine , Detroit, Michigan 48201, United States.
authors.forename: Glenn W
authors.initials: GW
authors.lastname: Kaatz
authors.affiliation: Department of Chemistry, Biology and Biotechnology, University of Perugia , 06123 Perugia, Italy.
authors.forename: Gabriele
authors.identifier: 0000-0002-4162-8692
authors.initials: G
authors.lastname: Cruciani
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015195:Drug Design; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D007211:Indoles