C2 Arylated Benzo[b]thiophene Derivatives as Staphylococcus aureus NorA Efflux Pump Inhibitors. Issue 3 (6th January 2016)

• Record Type: Journal Article
• Authors: Liger, François; Bouhours, Pascale; Ganem‐Elbaz, Carine; Jolivalt, Claude; Pellet‐Rostaing, Stéphane; Popowycz, Florence; Paris, Jean‐Marc; Lemaire, Marc
• Is Part Of: ChemMedChem. Volume 11:Issue 3(2016)
• Page Start: 320
• Page End: 330
• Publication Date: 2016-01-06
• Subjects: antibiotics -- arylation -- efflux pump inhibitors -- inhibitors -- sulfur heterocycles; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201500463
• Languages: English
• ISSNs: 1860-7179

Abstract

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. Abstract : Pump stoppers : Synthetic methods based on the regioselective functionalization of a benzo[ b ]thiophene derivative afford a series of original INF55 analogues as potential NorA pump inhibitors. Two derivatives display minimal inhibitory concentrations (MICs) of 0.25 and 0.5 µg mL −1, which is a promising result relative to that shown by reserpine (MIC=20 µg mL −1 ) a reference compound.