title: C2 Arylated Benzo[b]thiophene Derivatives as Staphylococcus aureus NorA Efflux Pump Inhibitors.
abstract: An innovative and straightforward synthesis of second-generation 2-arylbenzo[b]thiophenes as structural analogues of INF55 and the first generation of our laboratory-made molecules was developed. The synthesis of C2-arylated benzo[b]thiophene derivatives was achieved through a method involving direct arylation, followed by simple structural modifications. Among the 34 compounds tested, two of them were potent NorA pump inhibitors, which led to a 16-fold decrease in the ciprofloxacin minimum inhibitory concentration (MIC) against the SA-1199B strain at concentrations of 0.25 and 0.5 μg mL(-1) (1 and 1.5 μm, respectively). This is a promising result relative to that obtained for reserpine (MIC=20 μg mL(-1)), a reference compound amongst NorA pump inhibitors. These molecules thus represent promising candidates to be used in combination with ciprofloxacin against fluoroquinolone-resistant strains.
authors.affiliation: Equipe Catalyse Synthèse Environnement, CNRS-UMR 5246, L'Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), 43 Bd. du 11 novembre 1918, 69622, Villeurbanne, France.
authors.forename: François
authors.initials: F
authors.lastname: Liger
authors.affiliation: Laboratoire Charles Friedel, CNRS-UMR 7223, Chimie ParisTech, 11 rue Pierre et Marie Curie, 75005, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Bouhours
authors.affiliation: Laboratoire Charles Friedel, CNRS-UMR 7223, Chimie ParisTech, 11 rue Pierre et Marie Curie, 75005, Paris, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Ganem-Elbaz
authors.affiliation: Laboratoire Charles Friedel, CNRS-UMR 7223, Chimie ParisTech, 11 rue Pierre et Marie Curie, 75005, Paris, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Jolivalt
authors.affiliation: Equipe Catalyse Synthèse Environnement, CNRS-UMR 5246, L'Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), 43 Bd. du 11 novembre 1918, 69622, Villeurbanne, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pellet-Rostaing
authors.affiliation: Institut National des Sciences Appliquées de Lyon, ICBMS, CNRS-UMR 5246, Equipe Chimie Organique et Bioorganique, 20 Avenue Albert Einstein, 69621, Villeurbanne, France. Florence.Popowycz@insa-lyon.fr.
authors.forename: Florence
authors.initials: F
authors.lastname: Popowycz
authors.affiliation: Laboratoire Charles Friedel, CNRS-UMR 7223, Chimie ParisTech, 11 rue Pierre et Marie Curie, 75005, Paris, France. claude.jolivalt@upmc.fr.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Paris
authors.affiliation: Equipe Catalyse Synthèse Environnement, CNRS-UMR 5246, L'Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), 43 Bd. du 11 novembre 1918, 69622, Villeurbanne, France. marc.lemaire@univ-lyon1.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Lemaire
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors*; D013210:Staphylococcus / Q000737:chemistry / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D013876:Thiophenes; C088015:benzothiophene; C075040:NorA protein, Staphylococcus
keywords: antibiotics; arylation; efflux pump inhibitors; inhibitors; sulfur heterocycles