C2 Arylated Benzo[<i>b</i>]thiophene Derivatives as <i>Staphylococcus aureus</i> NorA Efflux Pump Inhibitors

Mouton-Liger, François; Bouhours, Pascale; Ganem‐Elbaz, Carine; Jolivalt, Claude; Pellet‐Rostaing, Stéphane; Popowycz, Florence; Paris, Jean‐Marc; Lemaire, Marc

doi:10.1002/cmdc.201500463

Cited by 19 publications

(12 citation statements)

References 72 publications

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“…7 Additional studies have shown that uniquely substituted benzo[ b ] thiophenes may be useful in the treatment of Staphylococcus infections. 8 Organic materials containing the benzothiophene core structure are showcased in devices including novel phosphorescent organic light emitting diodes (PHOLED’s) made possible by the low-lying LUMO and high thermal stability associated with aromatic heterocycles 9 ; organic thin-film field effect transistors (OFET’s) dependent on the high photostability and ionization potential of core-structure organics 10 ; and dye-sensitized solar cells (DSSC’s). 11…”

Section: Introductionmentioning

confidence: 99%

Sodium halides as the source of electrophilic halogens in green synthesis of 3-halo- and 3, n -dihalobenzo[ b ]thiophenes

et al. 2018

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A convenient methodology for the synthesis of mono- and di-halogenated benzo[b]thiophenes is described herein, which utilizes copper(II) sulfate pentahydrate and various sodium halides in the presence of substituted 2-alkynylthioanisoles. The proposed method is facile, uses ethanol as a green solvent, and results in uniquely substituted benzo[b]thiophene structures with isolated yields up to 96%. The most useful component of this methodology is the selective introduction of bromine atoms at every available position (2–7) around the benzo[b]thiophene ring, while keeping position 3 occupied by a specific halogen atom such as Cl, Br or I. Aromatic halogens are useful reactive handles; therefore, the selective introduction of halogens at specific positions would be valuable in the targeted synthesis of bioactive molecules and complex organic materials via metal-catalyzed cross coupling reactions. This work is a novel approach towards the synthesis of dihalo substituted benzo[b]thiophene core structures, which provides a superior alternative to the current methods discussed herein.

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Section: Introductionmentioning

confidence: 99%

Sodium halides as the source of electrophilic halogens in green synthesis of 3-halo- and 3, n -dihalobenzo[ b ]thiophenes

et al. 2018

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“…First, the effects of the compounds on the MICs of ciprofloxacin, an efflux substrate of the NorA systems, and erythromycin an efflux substrate of the MrsA systems, were measured against S. aureus SA-1 and S. aureus RN-4220 strains, respectively. The choice of the SA-1 strain instead of the SA-1199B strain (the most commonly used strain in NorA efflux pump inhibition assays [33][34][35] was because the former strain overexpresses the NorA efflux pump without having other mutations such as mutations in topoisomerase IV (A116E GrlA) previously reported in SA-1199B. [36] Then, compounds that resulted in the 4-fold decrease or more in the MIC of ciprofloxacin were assayed for their time-dose effects on the accumulation and on the efflux of ethidium bromide, a substrate of the NorA pump in the S. aureus SA-1 strain.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of 2‐Aminothiophene Derivatives as Staphylococcus aureus Efflux Pump Inhibitors

et al. 2020

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2-aminothiophene derivatives (2AT) in which the thiophene ring is fused with a cycloalkyl or a N-acylated piperidine ring by positions 5 and 6 and carrying a 3-carbethoxy group were synthesized and their bacterial growth and enzyme inhibitory effects against efflux proteins of Staphylococcus aureus leading to resistance to fluoroquinolones and erythromycin (ERY) were investigated. Compounds that most effectively decreases the minimum inhibitory concentrations (MICs) of ciprofloxacin (CIP) were assayed for their dose and time effects on the accumulation and efflux of ethidium bromide (EtBr) in the SA-1 strain. None of the compounds displayed antibacterial activity however, three derivatives carrying 2-amino, 2-aminoacetyl and 2-aminotrifluoroacetyl group enhanced the activity of CIP and ERY by 8-and 16-fold, respectively, and were able to restore the sensitivity of resistant strains, acting as typical efflux pump inhibitors (EPIs). The 2-aminoacetyl and 2-aminotrifluoroacetyl derivatives and two other piperidinyl 2-aminotrifluoroacetyl derivatives increased EtBr accumulation in a dose-and timedependent manner, and one of them was also able to inhibit the EtBr efflux. Taken together, these results represent an important advance in the development of new EPIs, and demonstrate that 2AT represent a good scaffold for developing new antibiotic adjuvants.[a] Dr.

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“…Liger et al also demonstrated that C2 arylated benzo[b]thiophene derivatives presented NorA pump inhibition in S. aureus and caused a 16‐fold decrease in the MIC value of ciprofloxacin [70] …”

Section: Resultsmentioning

confidence: 99%

Studies on Antimicrobial, Antibiofilm, Efflux Pump Inhibiting, and ADMET Properties of Newly Synthesized 1,3,4‐Thiadiazole Derivatives**

et al. 2021

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The novel compounds bearing 1,3,4‐thiadiazole moiety were obtained and their structures were identified using FT‐IR, NMR methods, elemental, and mass analysis. UV‐Vis and fluorescence spectra were obtained in six different polarity solvents. In addition, antimicrobial, antibiofilm, and the efflux pump inhibiting activities of the new compounds on K. pneumoniae, methicillin‐resistant S. aureus (MRSA), E. coli, and C. albicans were investigated. Furthermore, druglikeness and ADMET properties of the compounds were determined. As a result, it was observed that some of the derivatives presented antimicrobial activity against K. pneumoniae, S. aureus, and C. albicans. But the MBC/MFC test showed that all the activities were bacteriostatic. In addition, these derivatives have the potential of using both inhibiting and activating biofilm formation depending on the concentration. 1,3,4‐thiadiazole derivatives also presented good efflux pump inhibition in K. pneumoniae and E. coli. ADMET tests showed that 1,3,4‐thiadiazole derivatives have the potential of being used as therapeutic compounds.

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C2 Arylated Benzo[b]thiophene Derivatives as Staphylococcus aureus NorA Efflux Pump Inhibitors

Cited by 19 publications

References 72 publications

Sodium halides as the source of electrophilic halogens in green synthesis of 3-halo- and 3, n -dihalobenzo[ b ]thiophenes

Sodium halides as the source of electrophilic halogens in green synthesis of 3-halo- and 3, n -dihalobenzo[ b ]thiophenes

Synthesis and Evaluation of 2‐Aminothiophene Derivatives as Staphylococcus aureus Efflux Pump Inhibitors

Studies on Antimicrobial, Antibiofilm, Efflux Pump Inhibiting, and ADMET Properties of Newly Synthesized 1,3,4‐Thiadiazole Derivatives**

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