{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T09:17:04Z","timestamp":1774084624726,"version":"3.50.1"},"reference-count":65,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institutional Fund Projects","award":["IFPIP:742-130-1443"],"award-info":[{"award-number":["IFPIP:742-130-1443"]}]},{"name":"Ministry of Education and King Abdulaziz University, DSR, Jeddah, Saudi Arabia","award":["IFPIP:742-130-1443"],"award-info":[{"award-number":["IFPIP:742-130-1443"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where Staphylococcus aureus and its efflux pumps play a prominent role. The study\u2019s objective was to evaluate the potential of synthetic coumarins with different substitutions in the C-3 position as possible inhibitors of the NorA and MepA efflux pumps of S. aureus. For this evaluation, the following steps took place: (i) the determination of the minimum inhibitory concentration (MIC); (ii) the association of coumarins with fluoroquinolones and ethidium bromide (EtBr); (iii) the assessment of the effect on EtBr fluorescence emission; (iv) molecular docking; and (v) an analysis of the effect on membrane permeability. Coumarins reduced the MICs of fluoroquinolones and EtBr between 50% and 87.5%. Coumarin C1 increased EtBr fluorescence emission between 20 and 40% by reinforcing the evidence of efflux inhibition. The molecular docking results demonstrated that coumarins have an affinity with efflux pumps and establish mainly hydrogen bonds and hydrophobic interactions. Furthermore, C1 did not change the permeability of the membrane. Therefore, we conclude that these 3-substituted coumarins act as inhibitors of the NorA and MepA efflux pumps of S. aureus.<\/jats:p>","DOI":"10.3390\/antibiotics12121739","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T03:16:33Z","timestamp":1702610193000},"page":"1739","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["3-Substituted Coumarins Inhibit NorA and MepA Efflux Pumps of Staphylococcus aureus"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1240-3654","authenticated-orcid":false,"given":"Jos\u00e9 B. de","family":"Ara\u00fajo-Neto","sequence":"first","affiliation":[{"name":"Postgraduate Program in Biological Sciences, Biosciences Center, Federal University of Pernambuco, Recife 50740-570, PE, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1316-7064","authenticated-orcid":false,"given":"C\u00edcera D. de M.","family":"Oliveira-Tintino","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri, Crato 63105-000, CE, Brazil"}]},{"given":"Gild\u00eania A.","family":"de Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri, Crato 63105-000, CE, Brazil"}]},{"given":"Daniel S.","family":"Alves","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri, Crato 63105-000, CE, Brazil"}]},{"given":"Fernanda R.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Research Laboratory, Faculty of Pharmaceutical Sciences, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil"}]},{"given":"Guilherme A.","family":"Brancaglion","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Research Laboratory, Faculty of Pharmaceutical Sciences, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6362-2822","authenticated-orcid":false,"given":"Diogo T.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry Research Laboratory, Faculty of Pharmaceutical Sciences, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3150-9139","authenticated-orcid":false,"given":"Clara Mariana Gon\u00e7alves","family":"Lima","sequence":"additional","affiliation":[{"name":"Department of Food Science, Federal University of Lavras, Lavras 37203-202, MG, Brazil"}]},{"given":"Hani S. H.","family":"Mohammed Ali","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2752-0519","authenticated-orcid":false,"given":"Irfan A.","family":"Rather","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1838-1337","authenticated-orcid":false,"given":"Mohmmad Y.","family":"Wani","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, University of Jeddah, Jeddah 21589, Saudi Arabia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3188-2272","authenticated-orcid":false,"given":"Talha B.","family":"Emran","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA"},{"name":"Legorreta Cancer Center, Brown University, Providence, RI 02912, USA"},{"name":"Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6634-4207","authenticated-orcid":false,"given":"Henrique D. M.","family":"Coutinho","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri, Crato 63105-000, CE, Brazil"}]},{"given":"Valdir de Q.","family":"Balbino","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Biological Sciences, Biosciences Center, Federal University of Pernambuco, Recife 50740-570, PE, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7733-9331","authenticated-orcid":false,"given":"Saulo R.","family":"Tintino","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri, Crato 63105-000, CE, Brazil"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1080\/21505594.2021.1878688","article-title":"Pathogenicity and Virulence of Staphylococcus aureus","volume":"12","author":"Cheung","year":"2021","journal-title":"Virulence"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s41579-023-00852-y","article-title":"Staphylococcus aureus Host Interactions and Adaptation","volume":"21","author":"Howden","year":"2023","journal-title":"Nat. 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