title: Synthesis and evaluation of new arylbenzo[b]thiophene and diarylthiophene derivatives as inhibitors of the NorA multidrug transporter of Staphylococcus aureus.
abstract: The synthesis based on palladium catalytic coupling of 38 new-arylated benzo[b]thiophenes or thiophenes is described in a few steps. We also report the direct arylation of the position 3 of the benzo[b]thiophenic structure, a 'one pot' 2,5-heterodiarylation of thiophenes as well as the synthesis of precursors of amino-acids with a 2-arylated benzo[b]thiophene core. These compounds were evaluated on bacteria strains: most of them did not exhibit any antibiotic activity but were found to selectively inhibit the NorA multidrug transporter of Staphylococcus aureus. As such, they restored the activity of the NorA substrates ciprofloxacin against a resistant S. aureus strain in which this efflux pump is over-expressed.
authors.affiliation: ICBMS, Institut de chimie et BiochimieMoléculaire et Supramoléculaire, UMR-CNRS 5246, Université de Lyon, Université Claude Bernard Lyon 1, CPE Lyon, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Fournier Dit Chabert
authors.forename: Béatrice
authors.initials: B
authors.lastname: Marquez
authors.forename: Luc
authors.initials: L
authors.lastname: Neville
authors.forename: Lionel
authors.initials: L
authors.lastname: Joucla
authors.forename: Sylvie
authors.initials: S
authors.lastname: Broussous
authors.forename: Pascale
authors.initials: P
authors.lastname: Bouhours
authors.forename: Emilie
authors.initials: E
authors.lastname: David
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pellet-Rostaing
authors.forename: Bernard
authors.initials: B
authors.lastname: Marquet
authors.forename: Nicole
authors.initials: N
authors.lastname: Moreau
authors.forename: Marc
authors.initials: M
authors.lastname: Lemaire
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D002939:Ciprofloxacin / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D004996:Ethidium; D006801:Humans; D007202:Indicators and Reagents; D018942:Macrolides / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors*; D015363:Quinolones / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D002939:Ciprofloxacin; D004996:Ethidium; D007202:Indicators and Reagents; D018942:Macrolides; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015363:Quinolones; D013876:Thiophenes; C075040:NorA protein, Staphylococcus