{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:30:50Z","timestamp":1790188250252,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["308178\/2021\u20101"],"award-info":[{"award-number":["308178\/2021\u20101"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005283","name":"Funda\u00e7\u00e3o Cearense de Apoio ao Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["BP4\u20100172\u201000075.01.00\/20"],"award-info":[{"award-number":["BP4\u20100172\u201000075.01.00\/20"]}],"id":[{"id":"10.13039\/501100005283","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In recent years, bacterial resistance to traditional drugs has increased, and the need to find new effective antibiotics to treat infections caused by multidrug\u2010resistant bacteria has consequently become more important. The current study aimed to evaluate the potentiation of antibiotic activity and efflux pumps inhibition by (2<jats:italic>E<\/jats:italic>)\u20101\u2010(4\u2010aminophenyl)\u20103\u2010(4\u2010fluorophenyl)prop\u20102\u2010en\u20101\u2010one (PA\u2010Fluorine) against the standard and resistant bacterial strains of <jats:styled-content style=\"fixed-case\"><jats:italic>Staphylococcus aureus<\/jats:italic><\/jats:styled-content> and <jats:italic><jats:styled-content style=\"fixed-case\">Escherichia coli<\/jats:styled-content><\/jats:italic>. The association between PA\u2010Fluorine and ampicillin reduced the minimum inhibitory concentration (MIC), showing a synergistic effect against <jats:styled-content style=\"fixed-case\"><jats:italic>S.\u00a0aureus<\/jats:italic><\/jats:styled-content>. For <jats:italic><jats:styled-content style=\"fixed-case\">E.\u00a0coli<\/jats:styled-content><\/jats:italic>, PA\u2010Fluorine did not show any significant results when associated with ampicillin. Ciprofloxacin and chlorpromazine showed synergy with PA\u2010Fluorine on the two studied strains. An efflux pump mechanism was involved in the mechanism of action of chlorpromazine, norfloxacin, and ethidium bromide. PA\u2010Fluorine synergistically modulated norfloxacin and bromide. It was thus concluded that PA\u2010Fluorine has the potential to enhance antibacterial activity when combined with antibiotics. Molecular docking studies showed the effect of intermolecular interactions of PA\u2010Fluorine on the NorA and MepA efflux pumps. Physicochemical and pharmacokinetic properties were also obtained by ADMET studies for this chalcone, which presents be a strong candidate as an efflux pump inhibitor.<\/jats:p>","DOI":"10.1111\/fcp.12785","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T10:24:00Z","timestamp":1651055040000},"page":"1066-1082","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Potentiation of antibiotic activity, and efflux pumps inhibition by (2<i>E<\/i>)\u20101\u2010(4\u2010aminophenyl)\u20103\u2010(4\u2010fluorophenyl)prop\u20102\u2010en\u20101\u2010one"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3698-880X","authenticated-orcid":false,"given":"Paula","family":"Hem\u00edlia de Souza Nunes","sequence":"first","affiliation":[{"name":"Graduate Program in Biotechnology, Northeast Network of Biotechnology State University of Cear\u00e1, Campus Itaperi  Fortaleza CE Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0917-4715","authenticated-orcid":false,"given":"Thiago","family":"Sampaio de Freitas","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Chemistry, Department of Biological Chemistry Regional University of Cariri  Crato CE Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7680-0651","authenticated-orcid":false,"given":"Jana\u00edna","family":"Esmeraldo Rocha","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Chemistry, Department of Biological Chemistry Regional University of Cariri  Crato CE Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8205-7120","authenticated-orcid":false,"given":"Raimundo","family":"Luiz Silva Pereira","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Chemistry, Department of Biological Chemistry Regional University of Cariri  Crato CE Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7640-2220","authenticated-orcid":false,"given":"Marcia","family":"Machado Marinho","sequence":"additional","affiliation":[{"name":"Faculty of Education, Sciences and Letters of Iguatu State University of Cear\u00e1, Campus FECLI  Iguatu CE Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7450-1447","authenticated-orcid":false,"given":"Mateus Rodrigues","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Science and Technology Centre, Course of Chemistry State University Vale do Acara\u00fa  Sobral CE Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7125-134X","authenticated-orcid":false,"given":"Larissa","family":"Santos Oliveira","sequence":"additional","affiliation":[{"name":"Science and Technology Centre, Course of Chemistry State University Vale do Acara\u00fa  Sobral CE Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1548-8574","authenticated-orcid":false,"given":"Emanuelle","family":"Machado Marinho","sequence":"additional","affiliation":[{"name":"Group of Theoretical Chemistry and Electrochemistry State University of Cear\u00e1, Campus FAFIDAM  Limoeiro do Norte CE Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4774-8775","authenticated-orcid":false,"given":"Emmanuel","family":"Silva Marinho","sequence":"additional","affiliation":[{"name":"Department of Organic and Inorganic Chemistry Federal University of Cear\u00e1  Fortaleza CE Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2132-6862","authenticated-orcid":false,"given":"Silvia","family":"Sousa Aquino","sequence":"additional","affiliation":[{"name":"Graduate Program in Biotechnology, Northeast Network of Biotechnology State University of Cear\u00e1, Campus Itaperi  Fortaleza CE Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3554-3780","authenticated-orcid":false,"given":"Carlos","family":"Emidio Sampaio Nogueira","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Chemistry, Department of Biological Chemistry Regional University of Cariri  Crato CE Brazil"},{"name":"Department of Physics Regional University of Cariri  Juazeiro do Norte CE Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6634-4207","authenticated-orcid":false,"given":"Henrique","family":"Douglas Melo Coutinho","sequence":"additional","affiliation":[{"name":"Graduate Program in Biological Chemistry, Department of Biological Chemistry Regional University of Cariri  Crato CE Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5374-1839","authenticated-orcid":false,"given":"Paulo","family":"Nogueira Bandeira","sequence":"additional","affiliation":[{"name":"Science and Technology Centre, Course of Chemistry State University Vale do Acara\u00fa  Sobral CE Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6786-2076","authenticated-orcid":false,"given":"Alexandre","family":"Magno Rodrigues Teixeira","sequence":"additional","affiliation":[{"name":"Graduate Program in Biotechnology, Northeast Network of Biotechnology State University of Cear\u00e1, Campus Itaperi  Fortaleza CE Brazil"},{"name":"Graduate Program in Biological Chemistry, Department of Biological Chemistry Regional University of Cariri  Crato CE Brazil"},{"name":"Department of Physics Regional University of Cariri  Juazeiro do Norte CE Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5527-164X","authenticated-orcid":false,"given":"H\u00e9lcio Silva","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Graduate Program in Biotechnology, Northeast Network of Biotechnology State University of Cear\u00e1, Campus Itaperi  Fortaleza CE Brazil"},{"name":"Graduate Program in Biological Chemistry, Department of Biological Chemistry Regional University of Cariri  Crato CE Brazil"},{"name":"Science and Technology Centre, Course of Chemistry State University Vale do Acara\u00fa  Sobral CE Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2020.07.025"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.giant.2021.100066"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0NP00061B"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2019.1573812"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/femsle\/fnaa124"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2021.104894"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2021.105286"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2020.105695"},{"key":"e_1_2_9_10_1","unstructured":"20 NCCLS \u2013 NATIONAL COMMITTEE FOT CLINICAL LABORATORY STANDARDS.Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. NCCLS approved standard M7\u2010A5 (2000)."},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000151267"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2018.02.004"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.14715\/cmb\/2021.67.1.18"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084"},{"key":"e_1_2_9_15_1","unstructured":"HueyR MorrisGM ForliS.Using autodock 4 and autodock vina with autodocktools: a tutorial2012."},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758\u20102946\u20104\u201017"},{"key":"e_1_2_9_18_1","volume-title":"Dassault Systemes","author":"Discovery Studio Visualizer","year":"2017"},{"key":"e_1_2_9_19_1","unstructured":"CsizmadiaP.MarvinSketch and MarvinView: Molecule Applets for the World Wide Web.2019. doi:10.3390\/ecsoc\u20103\u201001775"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-987X(199604)17:5\/6<490::AID-JCC1>3.0.CO;2-P"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/wics.117"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640\u2010019\u201000142\u20107"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1049"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2021.1976277"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1818"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8995"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1308127110"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky427"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2020.104365"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci800084x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.2147\/AABC.S63749"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2010.11.002"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.6b00029"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1142\/S2737416521500137"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111768"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddtec.2004.11.007"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm020017n"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0492002"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13321\u2010018\u20100283\u2010x"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044\u2010019\u201002434\u20101"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1800"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10080995"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00465\u201020"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0251594"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.08.045"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7756-7_14"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.12.006"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201600182"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.5b00642"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.113.056267"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2018.00362"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci300400a"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.5b00131"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja305890c"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.12850"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408444.2011.598141"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2019.11.005"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03245929"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191838"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10593\u2010014\u20101496\u20101"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13321\u2010016\u20100117\u20107"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2017.04.008"}],"container-title":["Fundamental &amp; Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/fcp.12785","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/fcp.12785","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/fcp.12785","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T12:35:32Z","timestamp":1692621332000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/fcp.12785"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,19]]},"references-count":61,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1111\/fcp.12785"],"URL":"https:\/\/doi.org\/10.1111\/fcp.12785","archive":["Portico"],"relation":{},"ISSN":["0767-3981","1472-8206"],"issn-type":[{"value":"0767-3981","type":"print"},{"value":"1472-8206","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,19]]},"assertion":[{"value":"2022-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}