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Sciences","award":["PTDC\/CTA-AMB\/0853\/2021"],"award-info":[{"award-number":["PTDC\/CTA-AMB\/0853\/2021"]}]},{"name":"Hungarian Academy of Sciences","award":["CHIRALBIOACTIVE-PI-3RL-IINFACTS-2019"],"award-info":[{"award-number":["CHIRALBIOACTIVE-PI-3RL-IINFACTS-2019"]}]},{"name":"Hungarian Academy of Sciences","award":["CHIRALSINTESE_APSFCT_IINFACTS _2021"],"award-info":[{"award-number":["CHIRALSINTESE_APSFCT_IINFACTS _2021"]}]},{"name":"Hungarian Academy of Sciences","award":["SFRH\/BD\/147207\/2019"],"award-info":[{"award-number":["SFRH\/BD\/147207\/2019"]}]},{"name":"Hungarian Academy of Sciences","award":["SFRH\/BD\/144681\/2019"],"award-info":[{"award-number":["SFRH\/BD\/144681\/2019"]}]},{"name":"Hungarian Academy of Sciences","award":["BO\/00158\/22\/5"],"award-info":[{"award-number":["BO\/00158\/22\/5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Resistance to antibiotics is an emerging problem worldwide, which leads to an increase in morbidity and mortality rates. Several mechanisms are attributed to bacterial resistance, overexpression of efflux pumps being one of the most prominent. As an attempt to develop new effective antimicrobial drugs, which could be able to act against resistant bacterial strains and considering the antimicrobial potential of flavonoids and triazolyl flavonoid derivatives, in particular chalcones, a small library of chalcone derivatives was synthesized and evaluated for its potential to act as antimicrobials and\/or adjuvants in combination with antibiotics towards resistant bacteria. Although only compound 7 was able to act as antibacterial, compounds 1, 2, 4, 5, 7, and 9 revealed to be able to potentiate the activity of antibiotics in resistant bacteria. Moreover, five compounds (3, 5\u20138) demonstrated to be effective inhibitors of efflux pumps in Salmonella enterica serovar Typhimurium SL1344, and four compounds (1, 3, 7, and 10) showed higher ability than reserpine to inhibit biofilm formation of resistant Staphylococcus aureus 272123. Together, our results showed the potential of these compounds regarding reversion of bacterial resistance.<\/jats:p>","DOI":"10.3390\/ijms232214291","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T03:29:50Z","timestamp":1668742190000},"page":"14291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["New Chalcone\u2013Triazole Hybrids with Promising Antimicrobial Activity in Multidrug Resistance Strains"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5711-7598","authenticated-orcid":false,"given":"Daniela","family":"Pereira","sequence":"first","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, FFUP\u2014Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4201-2774","authenticated-orcid":false,"given":"Fernando","family":"Dur\u00e3es","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, FFUP\u2014Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, 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 Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6725 Szeged, Hungary"}]},{"given":"Joana","family":"Freitas-da-Silva","sequence":"additional","affiliation":[{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, Portugal"},{"name":"ICBAS\u2014Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2948-5809","authenticated-orcid":false,"given":"Eug\u00e9nia","family":"Pinto","sequence":"additional","affiliation":[{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, Portugal"},{"name":"Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6115-8811","authenticated-orcid":false,"given":"Paulo","family":"Martins-da-Costa","sequence":"additional","affiliation":[{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, Portugal"},{"name":"ICBAS\u2014Institute of Biomedical Sciences Abel Salazar, University of Porto, 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, FFUP\u2014Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4150-8532","authenticated-orcid":false,"given":"Marta","family":"Correia-da-Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, FFUP\u2014Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 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 Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 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, FFUP\u2014Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0715-1779","authenticated-orcid":false,"given":"Honorina","family":"Cidade","sequence":"additional","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, FFUP\u2014Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, 4450-208 Matosinhos, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"541340","DOI":"10.1155\/2014\/541340","article-title":"Multidrug Resistance: An Emerging Crisis","volume":"2014","author":"Tanwar","year":"2014","journal-title":"Interdiscip. Perspect. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Blanco, P., Hernando-Amado, S., Reales-Calderon, J.A., Corona, F., Lira, F., Alcalde-Rico, M., Bernardini, A., Sanchez, M.B., and Martinez, J.L. (2016). Bacterial Multidrug Efflux Pumps: Much More Than Antibiotic Resistance Determinants. Microorganisms, 4.","DOI":"10.3390\/microorganisms4010014"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1093\/jac\/dky042","article-title":"Role of bacterial efflux pumps in biofilm formation","volume":"73","author":"Alav","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Dur\u00e3es, F., Resende, D.I.S.P., Palmeira, A., Szemer\u00e9di, N., Pinto, M.M.M., Spengler, G., and Sousa, E. (2021). Xanthones Active against Multidrug Resistance and Virulence Mechanisms of Bacteria. Antibiotics, 10.","DOI":"10.3390\/antibiotics10050600"},{"key":"ref_5","first-page":"6030","article-title":"Medicinal Chemistry Updates on Bacterial Efflux Pump Modulators","volume":"25","author":"Pinto","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dur\u00e3es, F., Cravo, S., Freitas-Silva, J., Szemer\u00e9di, N., Martins-da-Costa, P., Pinto, E., Tiritan, M.E., Spengler, G., Fernandes, C., and Sousa, E. (2021). Enantioselectivity of Chiral Derivatives of Xanthones in Virulence Effects of Resistant Bacteria. Pharmaceuticals, 14.","DOI":"10.3390\/ph14111141"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Dur\u00e3es, F., Palmeira, A., Cruz, B., Freitas-Silva, J., Szemer\u00e9di, N., Gales, L., da Costa, P.M., Remi\u00e3o, F., Silva, R., and Pinto, M. (2021). Antimicrobial Activity of a Library of Thioxanthones and Their Potential as Efflux Pump Inhibitors. Pharmaceuticals, 14.","DOI":"10.3390\/ph14060572"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dur\u00e3es, F., Szemer\u00e9di, N., Kumla, D., Pinto, M., Kijjoa, A., Spengler, G., and Sousa, E. (2021). Metabolites from Marine-Derived Fungi as Potential Antimicrobial Adjuvants. Mar. Drugs, 19.","DOI":"10.3390\/md19090475"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e00717","DOI":"10.1016\/j.btre.2022.e00717","article-title":"Ferulic acid derivatives inhibiting Staphylococcus aureus tetK and MsrA efflux pumps","volume":"34","author":"Pinheiro","year":"2022","journal-title":"Biotechnol. Rep."},{"key":"ref_10","unstructured":"Qais, F.A., and Ahmad, I. (2022). In silico screening and in vitro validation of phytocompounds as multidrug efflux pump inhibitor against E. coli. J. Biomol. Struct. Dyn., 1\u201313."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1021\/acs.jmedchem.1c01349","article-title":"Mycobactin Analogues with Excellent Pharmacokinetic Profile Demonstrate Potent Antitubercular Specific Activity and Exceptional Efflux Pump Inhibition","volume":"65","author":"Shyam","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ijantimicag.2005.09.002","article-title":"Antimicrobial activity of flavonoids","volume":"26","author":"Cushnie","year":"2005","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3760","DOI":"10.1016\/j.bmc.2019.07.023","article-title":"Natural product derived promising anti-MRSA drug leads: A review","volume":"27","author":"Gatadi","year":"2019","journal-title":"Bioorg. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s11101-018-9591-z","article-title":"Comprehensive review of antimicrobial activities of plant flavonoids","volume":"18","author":"Bartoszewski","year":"2019","journal-title":"Phytochem. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Aparna, V., Dineshkumar, K., Mohanalakshmi, N., Velmurugan, D., and Hopper, W. (2014). Identification of Natural Compound Inhibitors for Multidrug Efflux Pumps of Escherichia coli and Pseudomonas aeruginosa Using In Silico High-Throughput Virtual Screening and In Vitro Validation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101840"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1055\/s-0032-1328259","article-title":"Sarothrin from Alkanna orientalis Is an Antimicrobial Agent and Efflux Pump Inhibitor","volume":"79","author":"Bame","year":"2013","journal-title":"Planta Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.phymed.2013.02.007","article-title":"Synergistic effects of diosmetin with erythromycin against ABC transporter over-expressed methicillin-resistant Staphylococcus aureus (MRSA) RN4220\/pUL5054 and inhibition of MRSA pyruvate kinase","volume":"20","author":"Chan","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.jep.2011.06.039","article-title":"Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase","volume":"137","author":"Chan","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1002\/ptr.2695","article-title":"Modulation of drug resistance in staphylococcus aureus by a kaempferol glycoside from herissantia tiubae (malvaceae)","volume":"23","author":"Silva","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1093\/jac\/dks005","article-title":"Novel inhibitory activity of the Staphylococcus aureus NorA efflux pump by a kaempferol rhamnoside isolated from Persea lingue Nees","volume":"67","author":"Holler","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4828","DOI":"10.3390\/molecules16064828","article-title":"Flavonoids from Praxelis clematidea R.M. King and Robinson Modulate Bacterial Drug Resistance","volume":"16","author":"Maia","year":"2011","journal-title":"Molecules"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4514","DOI":"10.1016\/j.bmc.2012.05.025","article-title":"Chalcone inhibitors of the NorA efflux pump in Staphylococcus aureus whole cells and enriched everted membrane vesicles","volume":"20","author":"Holler","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Jesus, A., Dur\u00e3es, F., Szemer\u00e9di, N., Freitas-Silva, J., da Costa, P.M., Pinto, E., Pinto, M., Spengler, G., Sousa, E., and Cidade, H. (2022). BDDE-Inspired Chalcone Derivatives to Fight Bacterial and Fungal Infections. Mar. Drugs, 20.","DOI":"10.3390\/md20050315"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"128743","DOI":"10.1016\/j.bmcl.2022.128743","article-title":"New diarylpentanoids and chalcones as potential antimicrobial adjuvants","volume":"67","author":"Moreira","year":"2022","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.bioorg.2018.01.016","article-title":"Design, synthesis, characterization, antimicrobial evaluation and molecular modeling studies of some dehydroacetic acid-chalcone-1,2,3-triazole hybrids","volume":"77","author":"Lal","year":"2018","journal-title":"Bioorg. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.ejmech.2018.05.055","article-title":"Synthesis, crystal structure and antimicrobial potential of some fluorinated chalcone-1,2,3-triazole conjugates","volume":"155","author":"Yadav","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Pereira, D., Pinto, M., Correia-da-Silva, M., and Cidade, H. (2022). Recent Advances in Bioactive Flavonoid Hybrids Linked by 1,2,3-Triazole Ring Obtained by Click Chemistry. Molecules, 27.","DOI":"10.3390\/molecules27010230"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Pereira, D., Gon\u00e7alves, C., Martins, B.T., Palmeira, A., Vasconcelos, V., Pinto, M., Almeida, J.R., Correia-da-Silva, M., and Cidade, H. (2021). Flavonoid Glycosides with a Triazole Moiety for Marine Antifouling Applications: Synthesis and Biological Activity Evaluation. Mar. Drugs, 19.","DOI":"10.3390\/md19010005"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1473-3099(17)30753-3","article-title":"Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis","volume":"18","author":"Tacconelli","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"426","DOI":"10.2166\/wh.2014.160","article-title":"High prevalence of multidrug-resistant Escherichia coli and Enterococcus spp. in river water, upstream and downstream of a wastewater treatment plant","volume":"12","author":"Bessa","year":"2014","journal-title":"J. Water Health"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1038\/s41467-019-10512-6","article-title":"In situ structure and assembly of the multidrug efflux pump AcrAB-TolC","volume":"10","author":"Shi","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.resmic.2017.11.001","article-title":"The hydrophobic trap\u2014The Achilles heel of RND efflux pumps","volume":"169","author":"Aron","year":"2018","journal-title":"Res. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"103790","DOI":"10.1016\/j.micpath.2019.103790","article-title":"Reserpine attenuates biofilm formation and virulence of Staphylococcus aureus","volume":"138","author":"Parai","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.3389\/fmicb.2019.02762","article-title":"Clinically Approved Drugs Inhibit the Staphylococcus aureus Multidrug NorA Efflux Pump and Reduce Biofilm Formation","volume":"10","author":"Zimmermann","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_35","first-page":"117","article-title":"Standard operating procedure (SOP) for disk diffusion-based quorum sensing inhibition assays","volume":"89","author":"Spengler","year":"2020","journal-title":"Acta Pharm. Hung."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e00908","DOI":"10.1128\/AEM.00908-19","article-title":"Efflux Pumps in Chromobacterium Species Increase Antibiotic Resistance and Promote Survival in a Coculture Competition Model","volume":"85","author":"Benomar","year":"2019","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/1099-0690(20021)2002:2<285::AID-EJOC285>3.0.CO;2-J","article-title":"Base-Induced Coupling of \u03b1-Azido Ketones with Aldehydes\u2014An Easy and Efficient Route to Trifunctionalized Synthons 2-Azido-3-hydroxy Ketones, 2-Acylaziridines, and 2-Acylspiroaziridines","volume":"2002","author":"Patonay","year":"2002","journal-title":"Eur. J. Org. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5687","DOI":"10.1073\/pnas.1114944109","article-title":"Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop","volume":"109","author":"Eicher","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.str.2005.11.015","article-title":"Conformational Flexibility in the Multidrug Efflux System Protein AcrA","volume":"14","author":"Mikolosko","year":"2006","journal-title":"Structure"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/35016007","article-title":"Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export","volume":"405","author":"Koronakis","year":"2000","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1107\/S0907444998009378","article-title":"Protein Data Bank (PDB): Database of three-dimensional structural information of biological macromolecules","volume":"54","author":"Sussman","year":"1998","journal-title":"Acta Cryst. D Biol. Cryst."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: Homology modelling of protein structures and complexes","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"D158","DOI":"10.1093\/nar\/gkw1099","article-title":"UniProt: The universal protein knowledgebase","volume":"45","author":"Apweiler","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Z\u00e1rate, S.G., Morales, P., \u015awiderek, K., Bolanos-Garcia, V.M., and Bastida, A. (2019). A Molecular Modeling Approach to Identify Novel Inhibitors of the Major Facilitator Superfamily of Efflux Pump Transporters. Antibiotics, 8.","DOI":"10.3390\/antibiotics8010025"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Sim\u00f5es, R.R., Aires-de-Sousa, M., Concei\u00e7\u00e3o, T., Antunes, F., da Costa, P.M., and de Lencastre, H. (2011). High Prevalence of EMRSA-15 in Portuguese Public Buses: A Worrisome Finding. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017630"},{"key":"ref_48","unstructured":"CLSI (2018). CLSI Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, Clinical and Laboratory Standards Institute. [11th ed.]."},{"key":"ref_49","unstructured":"(2008). CLSI Clinical and Laboratory Standards Institute: Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard (Standard No. CLSI Document M27-A3)."},{"key":"ref_50","unstructured":"(2008). CLSI Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi; Approved Standard\u2014Second Edition (Standard No. CLSI Document M38-A2)."},{"key":"ref_51","unstructured":"Franklin, R., and Cockerill, M.D. (2011). Performance Standards for Antimicrobial Susceptibility Testing, Twenty-First Informational Supplement M100-S21, Clinical and Laboratory Standards Institute (CLSI)."},{"key":"ref_52","first-page":"1071","article-title":"Efflux pump inhibiting properties of racemic phenothiazine derivatives and their enantiomers on the bacterial AcrAB-TolC system","volume":"28","author":"Spengler","year":"2014","journal-title":"In Vivo"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Kincses, A., Szab\u00f3, S., R\u00e1cz, B., Szemer\u00e9di, N., Watanabe, G., Saijo, R., Sekiya, H., Tamai, E., Moln\u00e1r, J., and Kawase, M. (2020). Benzoxazole-Based Metal Complexes to Reverse Multidrug Resistance in Bacteria. Antibiotics, 9.","DOI":"10.3390\/antibiotics9100649"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Nov\u00e9, M., Kincses, A., Szalontai, B., R\u00e1cz, B., Blair, J.M.A., Gonz\u00e1lez-Pr\u00e1dena, A., Benito-Lama, M., Dom\u00ednguez-\u00c1lvarez, E., and Spengler, G. (2020). Biofilm Eradication by Symmetrical Selenoesters for Food-Borne Pathogens. Microorganisms, 8.","DOI":"10.3390\/microorganisms8040566"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Gajd\u00e1cs, M., and Spengler, G. (2019). The Role of Drug Repurposing in the Development of Novel Antimicrobial Drugs: Non-Antibiotic Pharmacological Agents as Quorum Sensing-Inhibitors. Antibiotics, 8.","DOI":"10.3390\/antibiotics8040270"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1021\/acs.jnatprod.8b00326","article-title":"Terpenoids from Euphorbia pedroi as Multidrug-Resistance Reversers","volume":"81","author":"Ferreira","year":"2018","journal-title":"J. Nat. Prod."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14291\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:20:54Z","timestamp":1760145654000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/14291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,18]]},"references-count":56,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232214291"],"URL":"https:\/\/doi.org\/10.3390\/ijms232214291","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,18]]}}}