{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:19:46Z","timestamp":1768465186970,"version":"3.49.0"},"reference-count":48,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,8]],"date-time":"2022-05-08T00:00:00Z","timestamp":1651968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT (Foundation for Science and Technology)","award":["POCI-01\u20130145-FEDER-028736"],"award-info":[{"award-number":["POCI-01\u20130145-FEDER-028736"]}]},{"name":"FCT (Foundation for Science and Technology)","award":["NORTE-01-0145-FEDER-000040"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000040"]}]},{"name":"North Portugal Regional Operational Program (NORTE2020)","award":["POCI-01\u20130145-FEDER-028736"],"award-info":[{"award-number":["POCI-01\u20130145-FEDER-028736"]}]},{"name":"North Portugal Regional Operational Program (NORTE2020)","award":["NORTE-01-0145-FEDER-000040"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000040"]}]},{"name":"European Regional Development Fund (ERDF)","award":["POCI-01\u20130145-FEDER-028736"],"award-info":[{"award-number":["POCI-01\u20130145-FEDER-028736"]}]},{"name":"European Regional Development Fund (ERDF)","award":["NORTE-01-0145-FEDER-000040"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000040"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The growing number of infectious diseases around the world threatens the effective response of antibiotics, contributing to the increase in antibiotic resistance seen as a global health problem. Currently, one of the main challenges in antimicrobial drug discovery is the search for new compounds that not only exhibit antimicrobial activity, but can also potentiate the antimicrobial activity and revert antibiotics\u2019 resistance, through the interference with several mechanisms, including the inhibition of efflux pumps (EPs) and biofilm formation. Inspired by macroalgae brominated bromophenol BDDE with antimicrobial activity, a series of 18 chalcone derivatives, including seven chalcones (9\u201315), six dihydrochalcones (16\u201318, and 22\u201324) and five diarylpropanes (19\u201321, and 25 and 26), was prepared and evaluated for its antimicrobial activity and potential to fight antibiotic resistance. Among them, chalcones 13 and 14 showed promising antifungal activity against the dermatophyte clinical strain of Trichophyton rubrum, and all compounds reversed the resistance to vancomycin in Enterococcus faecalis B3\/101, with 9, 14, and 24 able to cause a four-fold decrease in the MIC of vancomycin against this strain. Compounds 17\u201324 displayed inhibition of EPs and the formation of biofilm by S. aureus 272123, suggesting that these compounds are inhibiting the EPs responsible for the extrusion of molecules involved in biofilm-related mechanisms. Interestingly, compounds 17\u201324 did not show cytotoxicity in mouse embryonic fibroblast cell lines (NIH\/3T3). Overall, the results obtained suggest the potential of dihydrochalcones 16\u201318 and 22\u201324, and diarylpropanes 19\u201321, 25 and 26, as hits for bacterial EPs inhibition, as they are effective in the inhibition of EPs, but present other features that are important in this matter, such as the lack of antibacterial activity and cytotoxicity.<\/jats:p>","DOI":"10.3390\/md20050315","type":"journal-article","created":{"date-parts":[[2022,5,8]],"date-time":"2022-05-08T21:31:20Z","timestamp":1652045480000},"page":"315","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["BDDE-Inspired Chalcone Derivatives to Fight Bacterial and Fungal Infections"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7425-9750","authenticated-orcid":false,"given":"Ana","family":"Jesus","sequence":"first","affiliation":[{"name":"Laboratory of Organic and Pharmaceutical Chemistry, Department of 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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, Semmelweis utca 6, 6725 Szeged, Hungary"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0235-4991","authenticated-orcid":false,"given":"Joana","family":"Freitas-Silva","sequence":"additional","affiliation":[{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos, 4450-208 Matosinhos, Portugal"},{"name":"ICBAS\u2014Institute of Biomedical Sciences Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6115-8811","authenticated-orcid":false,"given":"Paulo Martins","family":"da Costa","sequence":"additional","affiliation":[{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos, 4450-208 Matosinhos, Portugal"},{"name":"ICBAS\u2014Institute of Biomedical Sciences Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira 228, 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, Avenida General Norton de Matos, 4450-208 Matosinhos, Portugal"},{"name":"Laboratory of Microbiology, Department of Biological Sciences, 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 Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos, 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, 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 Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos, 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, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2014Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida 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(2020). Synthesis of a Small Library of Nature-Inspired Xanthones and Study of Their Antimicrobial Activity. Molecules, 25.","DOI":"10.3390\/molecules25102405"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"470","DOI":"10.3389\/fmicb.2016.00470","article-title":"Antimicrobial Drugs in Fighting against Antimicrobial Resistance","volume":"7","author":"Cheng","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nrmicro2312","article-title":"Call of the wild: Antibiotic resistance genes in natural environments","volume":"8","author":"Allen","year":"2010","journal-title":"Nat. Rev. Micro."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nrd3975","article-title":"Platforms for antibiotic discovery","volume":"12","author":"Lewis","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"37007","DOI":"10.1039\/C7RA03859C","article-title":"Investigation on the effect of known potent S. aureus NorA efflux pump inhibitors on the staphylococcal biofilm formation","volume":"7","author":"Sabatini","year":"2017","journal-title":"RSC Adv."},{"key":"ref_7","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_8","first-page":"3812","article-title":"Chalcones: A privileged scaffold with diverse biological activities","volume":"20","author":"Singh","year":"2020","journal-title":"Plant Arch."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"111980","DOI":"10.1016\/j.ejmech.2019.111980","article-title":"Recent developments of chalcones as potential antibacterial agents in medicinal chemistry","volume":"187","author":"Dan","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Rezende-Junior, L.M., Andrade, L.M.S., Leal, A., Mesquita, A.B.S., Santos, A., Neto, J.S.L., Siqueira-Junior, J.P., Nogueira, C.E.S., Kaatz, G.W., and Coutinho, H.D.M. (2020). Chalcones Isolated from Arrabidaea brachypoda Flowers as Inhibitors of NorA and MepA Multidrug Efflux Pumps of Staphylococcus aureus. Antibiotics, 9.","DOI":"10.3390\/antibiotics9060351"},{"key":"ref_11","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_12","first-page":"3061","article-title":"Synthesis and Antibacterial Evaluation of new Ofloxacin-Chalcone derivatives Conjugates as Possible Mutual Prodrugs","volume":"10","author":"Hasan","year":"2018","journal-title":"J. Pharm. Sci. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s11164-012-0665-z","article-title":"Syntheses and biological activity of chalcones-imidazole derivatives","volume":"39","author":"Liu","year":"2012","journal-title":"Res. Chem. Intermed."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"H145","DOI":"10.1111\/j.1750-3841.2010.01629.x","article-title":"Alpha-glucosidase inhibitory activity of bromophenol purified from the red alga Polyopes lancifolia","volume":"75","author":"Kim","year":"2010","journal-title":"J. Food Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1021\/np980324p","article-title":"Two New Bromophenols from the Red Alga Odonthalia corymbifera","volume":"62","author":"Kurihara","year":"1999","journal-title":"J. Nat. Prod."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1021\/np020528c","article-title":"Bromophenols from the Red Alga Rhodomela confervoides","volume":"66","author":"Fan","year":"2003","journal-title":"J. Nat. Prod."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1021\/np0400609","article-title":"Dibenzyl Bromophenols with Diverse Dimerization Patterns from the Brown Alga Leathesia nana","volume":"67","author":"Xu","year":"2004","journal-title":"J. Nat. Prod."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Jesus, A., Correia-da-Silva, M., Afonso, C., Pinto, M., and Cidade, H. (2019). Isolation and Potential Biological Applications of Haloaryl Secondary Metabolites from Macroalgae. Mar. Drugs, 17.","DOI":"10.3390\/md17020073"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/S0031-9422(03)00004-9","article-title":"Antibacterial bromophenols from the marine red alga Rhodomela confervoides","volume":"62","author":"Xu","year":"2003","journal-title":"Phytochemistry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3838","DOI":"10.3390\/md12073838","article-title":"Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether, a marine algae derived bromophenol, inhibits the growth of Botrytis cinerea and interacts with DNA molecules","volume":"12","author":"Liu","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_21","unstructured":"Biediger, R.J.B., Michele, A., Lindsay Bonner, H., Vincent, A.B., Robert, V.M., Thomas, P.T., and Brandon, M.Y. (2018). Preparation of Propionic Acid Derivatives for Inhibiting the Binding of an Integrin. (U.S. Patent 20180312523)."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1002\/anie.201813071","article-title":"Pd-Catalyzed Enantioselective Ring Opening\/Cross-Coupling and Cyclopropanation of Cyclobutanones","volume":"58","author":"Cao","year":"2019","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_23","unstructured":"Meng, C.Q.N.L., Sikorski, J.A., and Hoong, L.K. (2001). Preparation of 1,3-bis-(substituted-phenyl)-2-propen-1-ones as VCAM-1 Inhibitors for Treatment of Inflammatory Disorders. (U.S. Patent WO 2001098291)."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111752","DOI":"10.1016\/j.ejmech.2019.111752","article-title":"Chalcone derivatives targeting mitosis: Synthesis, evaluation of antitumor activity and lipophilicity","volume":"184","author":"Pinto","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4486","DOI":"10.1021\/ja01646a072","article-title":"The preparation of chalcones from hydroxy and methoxy aldehydes and ketones","volume":"76","author":"Smith","year":"1954","journal-title":"J. Am. Chem. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0960-894X(00)00032-9","article-title":"Rational design, synthesis and structure-activity relationships of antitumor (E)-2-benzylidene-1-tetralones and (E)-2-benzylidene-1-indanones","volume":"10","author":"Shih","year":"2000","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/j.bmcl.2017.02.038","article-title":"Synthesis and biological evaluation of chalcone, dihydrochalcone, and 1,3-diarylpropane analogs as anti-inflammatory agents","volume":"27","author":"Hung","year":"2017","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1002\/jhet.5570230401","article-title":"Hexahydro-5,6,6a,7,12,14 isoquino[2,3-b]benzaz\u00e9pine-2. Nouvelle voie d\u2019acc\u00e8s","volume":"23","author":"Henin","year":"1986","journal-title":"J. Heterocycl. Chem."},{"key":"ref_29","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_30","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_31","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1002\/ptr.6042","article-title":"Bioactive compounds from the African medicinal plant Cleistochlamys kirkii as resistance modifiers in bacteria","volume":"32","author":"Kincses","year":"2018","journal-title":"Phytother. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1002\/ptr.6294","article-title":"Nigella sativa essential oil and its bioactive compounds as resistance modifiers against Staphylococcus aureus","volume":"33","author":"Mouwakeh","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"710","DOI":"10.3389\/fgene.2018.00710","article-title":"Genetic Diversity of norA, Coding for a Main Efflux Pump of Staphylococcus aureus","volume":"9","author":"Costa","year":"2019","journal-title":"Front. Genet."},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/513481a","article-title":"Chemical con artists foil drug discovery","volume":"513","author":"Baell","year":"2014","journal-title":"Nature"},{"key":"ref_36","unstructured":"M07, C.S. (2018). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, Clinical and Laboratory Standards Institute. [11th ed.]."},{"key":"ref_37","unstructured":"Clinical and Laboratory Standards Institute (2008). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts, Clinical and Laboratory Standards Institute. Approved standard\u2014CLSI document M27-A3."},{"key":"ref_38","unstructured":"Clinical and Laboratory Standards Institute (2008). Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi, Clinical and Laboratory Standards Institute. Approved Standard\u2014Second Edition, CLSI document M38-A2."},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"3970","DOI":"10.1038\/s41467-020-17735-y","article-title":"Efflux pump activity potentiates the evolution of antibiotic resistance across S. aureus isolates","volume":"11","author":"Papkou","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_41","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_42","doi-asserted-by":"crossref","unstructured":"(2017). UniProt: The universal protein knowledgebase. Nucleic Acids Res., 45, D158\u2013D169.","DOI":"10.1093\/nar\/gkw1099"},{"key":"ref_43","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_44","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1093\/jac\/42.6.807","article-title":"The effect of reserpine, an inhibitor of multidrug efflux pumps, on the in vitro activities of ciprofloxacin, sparfloxacin and moxifloxacin against clinical isolates of Staphylococcus aureus","volume":"42","author":"Schmitz","year":"1998","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_45","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_46","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s10822-010-9352-6","article-title":"Ligand docking and binding site analysis with PyMOL and Autodock\/Vina","volume":"24","author":"Seeliger","year":"2010","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_47","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_48","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":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/5\/315\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:07:57Z","timestamp":1760137677000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/5\/315"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,8]]},"references-count":48,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["md20050315"],"URL":"https:\/\/doi.org\/10.3390\/md20050315","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,8]]}}}