Modulation of Drug Resistance in Staphylococcus aureus with Coumarin Derivatives

Semisynthetic and commercial coumarins were investigated for their antibacterial and adjuvant properties with antibiotic agents against norfloxacin, erythromycin, and tetracycline resistant Staphylococcus aureus as based on efflux mechanisms. The coumarins and certain commercial antibiotics had thei...

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Main Authors: Rodrigo Santos Aquino de Araújo, José Maria Barbosa-Filho, Marcus Tullius Scotti, Luciana Scotti, Ryldene Marques Duarte da Cruz, Vivyanne dos Santos Falcão-Silva, José Pinto de Siqueira-Júnior, Francisco Jaime Bezerra Mendonça-Junior
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Scientifica
Online Access:http://dx.doi.org/10.1155/2016/6894758
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author Rodrigo Santos Aquino de Araújo
José Maria Barbosa-Filho
Marcus Tullius Scotti
Luciana Scotti
Ryldene Marques Duarte da Cruz
Vivyanne dos Santos Falcão-Silva
José Pinto de Siqueira-Júnior
Francisco Jaime Bezerra Mendonça-Junior
author_facet Rodrigo Santos Aquino de Araújo
José Maria Barbosa-Filho
Marcus Tullius Scotti
Luciana Scotti
Ryldene Marques Duarte da Cruz
Vivyanne dos Santos Falcão-Silva
José Pinto de Siqueira-Júnior
Francisco Jaime Bezerra Mendonça-Junior
author_sort Rodrigo Santos Aquino de Araújo
collection DOAJ
description Semisynthetic and commercial coumarins were investigated for their antibacterial and adjuvant properties with antibiotic agents against norfloxacin, erythromycin, and tetracycline resistant Staphylococcus aureus as based on efflux mechanisms. The coumarins and certain commercial antibiotics had their Minimum Inhibitory Concentrations determined by broth microdilution assay against resistant S. aureus strains which overexpress efflux pump proteins. For evaluation of the modulatory activity, the antibiotics MICs were determined in the presence of the coumarin derivatives at subinhibitory concentration. Although the coumarins did not display relevant antibacterial activity (MIC ≥ 128 µg/mL), they did modulate the antibiotics activities. Various coumarins, especially the alkylated derivatives in combination with antibiotics at subinhibitory concentrations, modulated antibiotic activity, reducing the MIC for tetracycline and norfloxacin by 2 to 8 times. Polar Surface Area (PSA) studies were performed and the fact that the presence of apolar groups is an important factor for the modulatory activity of coumarins was corroborated. Docking on the Penicillin-Binding Protein from MRSA identified that 18 is a potential ligand presenting low Ebinding. The results indicate that coumarin derivatives modulated antibiotic resistance and may be used as potential antibiotic adjuvants, acting by bacterial efflux pump inhibition in S. aureus.
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spelling doaj-art-8cff6f8aa20a4583abfc4af768b577412025-08-20T02:09:34ZengWileyScientifica2090-908X2016-01-01201610.1155/2016/68947586894758Modulation of Drug Resistance in Staphylococcus aureus with Coumarin DerivativesRodrigo Santos Aquino de Araújo0José Maria Barbosa-Filho1Marcus Tullius Scotti2Luciana Scotti3Ryldene Marques Duarte da Cruz4Vivyanne dos Santos Falcão-Silva5José Pinto de Siqueira-Júnior6Francisco Jaime Bezerra Mendonça-Junior7Post-Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, 58051-900 João Pessoa, PB, BrazilPost-Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, 58051-900 João Pessoa, PB, BrazilPost-Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, 58051-900 João Pessoa, PB, BrazilPost-Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, 58051-900 João Pessoa, PB, BrazilLaboratory of Genetics of Microorganisms, Molecular Biology Department, Federal University of Paraíba, 58051-900 João Pessoa, PB, BrazilPost-Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, 58051-900 João Pessoa, PB, BrazilPost-Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, 58051-900 João Pessoa, PB, BrazilPost-Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, 58051-900 João Pessoa, PB, BrazilSemisynthetic and commercial coumarins were investigated for their antibacterial and adjuvant properties with antibiotic agents against norfloxacin, erythromycin, and tetracycline resistant Staphylococcus aureus as based on efflux mechanisms. The coumarins and certain commercial antibiotics had their Minimum Inhibitory Concentrations determined by broth microdilution assay against resistant S. aureus strains which overexpress efflux pump proteins. For evaluation of the modulatory activity, the antibiotics MICs were determined in the presence of the coumarin derivatives at subinhibitory concentration. Although the coumarins did not display relevant antibacterial activity (MIC ≥ 128 µg/mL), they did modulate the antibiotics activities. Various coumarins, especially the alkylated derivatives in combination with antibiotics at subinhibitory concentrations, modulated antibiotic activity, reducing the MIC for tetracycline and norfloxacin by 2 to 8 times. Polar Surface Area (PSA) studies were performed and the fact that the presence of apolar groups is an important factor for the modulatory activity of coumarins was corroborated. Docking on the Penicillin-Binding Protein from MRSA identified that 18 is a potential ligand presenting low Ebinding. The results indicate that coumarin derivatives modulated antibiotic resistance and may be used as potential antibiotic adjuvants, acting by bacterial efflux pump inhibition in S. aureus.http://dx.doi.org/10.1155/2016/6894758
spellingShingle Rodrigo Santos Aquino de Araújo
José Maria Barbosa-Filho
Marcus Tullius Scotti
Luciana Scotti
Ryldene Marques Duarte da Cruz
Vivyanne dos Santos Falcão-Silva
José Pinto de Siqueira-Júnior
Francisco Jaime Bezerra Mendonça-Junior
Modulation of Drug Resistance in Staphylococcus aureus with Coumarin Derivatives
Scientifica
title Modulation of Drug Resistance in Staphylococcus aureus with Coumarin Derivatives
title_full Modulation of Drug Resistance in Staphylococcus aureus with Coumarin Derivatives
title_fullStr Modulation of Drug Resistance in Staphylococcus aureus with Coumarin Derivatives
title_full_unstemmed Modulation of Drug Resistance in Staphylococcus aureus with Coumarin Derivatives
title_short Modulation of Drug Resistance in Staphylococcus aureus with Coumarin Derivatives
title_sort modulation of drug resistance in staphylococcus aureus with coumarin derivatives
url http://dx.doi.org/10.1155/2016/6894758
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