{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T19:04:38Z","timestamp":1768676678473,"version":"3.49.0"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04423\/2020, UIDP\/04423\/2020 (Group of Natural Products and Medicinal Chemistry - CIIMAR), and under the project PTDC\/SAU-PUB\/28736\/2017 (reference POCI-01\u20130145-FEDER-028736), co-financed by COMPETE 2020, Portugal 2020 and the European Union through t"],"award-info":[{"award-number":["UIDB\/04423\/2020, UIDP\/04423\/2020 (Group of Natural Products and Medicinal Chemistry - CIIMAR), and under the project PTDC\/SAU-PUB\/28736\/2017 (reference POCI-01\u20130145-FEDER-028736), co-financed by COMPETE 2020, Portugal 2020 and the European Union through t"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The overexpression of efflux pumps is one of the causes of multidrug resistance, which leads to the inefficacy of drugs. This plays a pivotal role in antimicrobial resistance, and the most notable pumps are the AcrAB-TolC system (AcrB belongs to the resistance-nodulation-division family) and the NorA, from the major facilitator superfamily. In bacteria, these structures can also favor virulence and adaptation mechanisms, such as quorum-sensing and the formation of biofilm. In this study, the design and synthesis of a library of thioxanthones as potential efflux pump inhibitors are described. The thioxanthone derivatives were investigated for their antibacterial activity and inhibition of efflux pumps, biofilm formation, and quorum-sensing. The compounds were also studied for their potential to interact with P-glycoprotein (P-gp, ABCB1), an efflux pump present in mammalian cells, and for their cytotoxicity in both mouse fibroblasts and human Caco-2 cells. The results concerning the real-time ethidium bromide accumulation may suggest a potential bacterial efflux pump inhibition, which has not yet been reported for thioxanthones. Moreover, in vitro studies in human cells demonstrated a lack of cytotoxicity for concentrations up to 20 \u00b5M in Caco-2 cells, with some derivatives also showing potential for P-gp modulation.<\/jats:p>","DOI":"10.3390\/ph14060572","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T21:24:29Z","timestamp":1623792269000},"page":"572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Antimicrobial Activity of a Library of Thioxanthones and Their Potential as Efflux Pump Inhibitors"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4201-2774","authenticated-orcid":false,"given":"Fernando","family":"Dur\u00e3es","sequence":"first","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Novo Edif\u00edcio do Terminal de Cruzeiros do Porto de Leix\u00f5es, Avenida General Norton de Matos, S\/N, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1391-2143","authenticated-orcid":false,"given":"Andreia","family":"Palmeira","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Novo Edif\u00edcio do Terminal de Cruzeiros do Porto de Leix\u00f5es, Avenida General Norton de Matos, S\/N, 4450-208 Matosinhos, Portugal"}]},{"given":"B\u00e1rbara","family":"Cruz","sequence":"additional","affiliation":[{"name":"UCIBIO-REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0235-4991","authenticated-orcid":false,"given":"Joana","family":"Freitas-Silva","sequence":"additional","affiliation":[{"name":"CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Novo Edif\u00edcio do Terminal de Cruzeiros do Porto de Leix\u00f5es, Avenida General Norton de Matos, S\/N, 4450-208 Matosinhos, Portugal"},{"name":"ICBAS\u2013Institute of Biomedical Sciences Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8638-5815","authenticated-orcid":false,"given":"Nikoletta","family":"Szemer\u00e9di","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Albert Szent-Gy\u00f6rgyi Health Center and Faculty of Medicine, University of Szeged, Semmelweis utca 6, 6725 Szeged, Hungary"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8352-6539","authenticated-orcid":false,"given":"Lu\u00eds","family":"Gales","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, ICBAS\u2013Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Bioengineering & Synthetic Microbiology, I3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6115-8811","authenticated-orcid":false,"given":"Paulo Martins","family":"da Costa","sequence":"additional","affiliation":[{"name":"CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Novo Edif\u00edcio do Terminal de Cruzeiros do Porto de Leix\u00f5es, Avenida General Norton de Matos, S\/N, 4450-208 Matosinhos, Portugal"},{"name":"ICBAS\u2013Institute of Biomedical Sciences Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1382-5119","authenticated-orcid":false,"given":"Fernando","family":"Remi\u00e3o","sequence":"additional","affiliation":[{"name":"UCIBIO-REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9962-7548","authenticated-orcid":false,"given":"Renata","family":"Silva","sequence":"additional","affiliation":[{"name":"UCIBIO-REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4676-1409","authenticated-orcid":false,"given":"Madalena","family":"Pinto","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"CIIMAR-Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Novo Edif\u00edcio do Terminal de Cruzeiros do Porto de Leix\u00f5es, Avenida General Norton de Matos, S\/N, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8085-0950","authenticated-orcid":false,"given":"Gabriella","family":"Spengler","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Albert Szent-Gy\u00f6rgyi Health Center and Faculty of Medicine, University of Szeged, Semmelweis utca 6, 6725 Szeged, Hungary"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5397-4672","authenticated-orcid":false,"given":"Em\u00edlia","family":"Sousa","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge 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