{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T18:30:45Z","timestamp":1777055445020,"version":"3.51.4"},"reference-count":60,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T00:00:00Z","timestamp":1629849600000},"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 n"],"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 n"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Marine-derived fungi constitute an interesting source of bioactive compounds, several of which exhibit antibacterial activity. These acquire special importance, considering that antimicrobial resistance is becoming more widespread. The overexpression of efflux pumps, capable of expelling antimicrobials out of bacterial cells, is one of the most worrisome mechanisms. There has been an ongoing effort to find not only new antimicrobials, but also compounds that can block resistance mechanisms which can be used in combination with approved antimicrobial drugs. In this work, a library of nineteen marine natural products, isolated from marine-derived fungi of the genera Neosartorya and Aspergillus, was evaluated for their potential as bacterial efflux pump inhibitors as well as the antimicrobial-related mechanisms, such as inhibition of biofilm formation and quorum-sensing. Docking studies were performed to predict their efflux pump action. These compounds were also tested for their cytotoxicity in mouse fibroblast cell line NIH\/3T3. The results obtained suggest that the marine-derived fungal metabolites are a promising source of compounds with potential to revert antimicrobial resistance and serve as an inspiration for the synthesis of new antimicrobial drugs.<\/jats:p>","DOI":"10.3390\/md19090475","type":"journal-article","created":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T04:24:27Z","timestamp":1629865467000},"page":"475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Metabolites from Marine-Derived Fungi as Potential Antimicrobial Adjuvants"],"prefix":"10.3390","volume":"19","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\u2013Interdisciplinary 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\/0000-0002-8638-5815","authenticated-orcid":false,"given":"Nikoletta","family":"Szemer\u00e9di","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Albert Szent-Gy\u00f6rgyi Health Center, Faculty of Medicine, University of Szeged, Semmelweis utca 6, 6725 Szeged, Hungary"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1434-3958","authenticated-orcid":false,"given":"Decha","family":"Kumla","sequence":"additional","affiliation":[{"name":"CIIMAR\u2013Interdisciplinary 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\/0000-0002-4676-1409","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\u2013Interdisciplinary 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\/0000-0002-3321-1061","authenticated-orcid":false,"given":"Anake","family":"Kijjoa","sequence":"additional","affiliation":[{"name":"CIIMAR\u2013Interdisciplinary 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\/0000-0001-8085-0950","authenticated-orcid":false,"given":"Gabriella","family":"Spengler","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Albert Szent-Gy\u00f6rgyi Health Center, 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 Viterbo Ferreira, 228, 4050-313 Porto, Portugal"},{"name":"CIIMAR\u2013Interdisciplinary 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"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sun, W., Wu, W., Liu, X., Zaleta-Pinet, D.A., and Clark, B.R. (2019). Bioactive Compounds Isolated from Marine-Derived Microbes in China: 2009\u20132018. Mar. Drugs, 17.","DOI":"10.3390\/md17060339"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/j.1751-7915.2010.00179.x","article-title":"Bioactive compounds from marine bacteria and fungi","volume":"3","author":"Debbab","year":"2010","journal-title":"Microb. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s42995-019-00021-2","article-title":"Metabolites from marine invertebrates and their symbiotic microorganisms: Molecular diversity discovery, mining, and application","volume":"1","author":"Liu","year":"2019","journal-title":"Mar. Life Sci. Technol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"B\u00f6ttcher, S., Di Capua, A., Blunt, J.W., and Quinn, R.J. (2018). Bioinspiration from Marine Scaffolds. Blue Biotechnology, Wiley-VCH Verlag GmbH & Co.","DOI":"10.1002\/9783527801718.ch10"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Rampelotto, P.H., and Trincone, A. (2018). The Marine Ecosystem as a Source of Antibiotics. Grand Challenges in Marine Biotechnology, Springer International Publishing.","DOI":"10.1007\/978-3-319-69075-9"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1080\/07388551.2019.1710457","article-title":"Marine bacteria as source of antimicrobial compounds","volume":"40","author":"Stincone","year":"2020","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s11101-020-09705-5","article-title":"Antimicrobial compounds from marine fungi","volume":"20","author":"Wang","year":"2021","journal-title":"Phytochem. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4617","DOI":"10.3390\/md13084617","article-title":"Lindgomycin, an Unusual Antibiotic Polyketide from a Marine Fungus of the Lindgomycetaceae","volume":"13","author":"Wu","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3479","DOI":"10.3390\/md13063479","article-title":"Antibacterial and Antifungal Compounds from Marine Fungi","volume":"13","author":"Xu","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3389\/fmars.2020.00313","article-title":"Anti-phytopathogenic Bacterial Metabolites From the Seaweed-Derived Fungus Aspergillus sp. D40","volume":"7","author":"Huang","year":"2020","journal-title":"Front. Mar. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1007\/s10126-013-9506-3","article-title":"Marine-Derived Aspergillus Species as a Source of Bioactive Secondary Metabolites","volume":"15","author":"Lee","year":"2013","journal-title":"Mar. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"17116","DOI":"10.1039\/D1RA01359A","article-title":"Recent updates on the bioactive compounds of the marine-derived genus Aspergillus","volume":"11","author":"Orfali","year":"2021","journal-title":"RSC Adv."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Prompanya, C., Dethoup, T., Gales, L., Lee, M., Pereira, J.A., Silva, A.M., Pinto, M.M., and Kijjoa, A. (2016). New Polyketides and New Benzoic Acid Derivatives from the Marine Sponge-Associated Fungus Neosartorya quadricincta KUFA 0081. Mar. Drugs, 14.","DOI":"10.3390\/md14070134"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ying, Y.-M., Huang, L., Tian, T., Li, C.-Y., Wang, S.-L., Ma, L.-F., Shan, W.-G., Wang, J.-W., and Zhan, Z.-J. (2018). Studies on the Chemical Diversities of Secondary Metabolites Produced by Neosartorya fischeri via the OSMAC Method. Molecules, 23.","DOI":"10.3390\/molecules23112772"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.3390\/md11062054","article-title":"Bioactive Phenylalanine Derivatives and Cytochalasins from the Soft Coral-Derived Fungus, Aspergillus elegans","volume":"11","author":"Zheng","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"822","DOI":"10.3390\/md12020822","article-title":"Antibacterial and antibiofilm activities of tryptoquivalines and meroditerpenes isolated from the marine-derived fungi Neosartorya paulistensis, N. laciniosa, N. tsunodae, and the soil fungi N. fischeri and N. siamensis","volume":"12","author":"Gomes","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"112575","DOI":"10.1016\/j.phytochem.2020.112575","article-title":"1,3-Dioxepine and spiropyran derivatives of viomellein and other dimeric naphthopyranones from cultures of Aspergillus elegans KUFA0015 and their antibacterial activity","volume":"181","author":"Kumla","year":"2021","journal-title":"Phytochemistry"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"May Zin, W.W., Buttachon, S., Dethoup, T., Fernandes, C., Cravo, S., Pinto, M.M., Gales, L., Pereira, J.A., Silva, A.M., and Sekeroglu, N. (2016). New Cyclotetrapeptides and a New Diketopiperzine Derivative from the Marine Sponge-Associated Fungus Neosartorya glabra KUFA 0702. Mar. Drugs, 14.","DOI":"10.3390\/md14070136"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3776","DOI":"10.3390\/md13063776","article-title":"A New Meroditerpene and a New Tryptoquivaline Analog from the Algicolous Fungus Neosartorya takakii KUFC 7898","volume":"13","author":"Zin","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S122","DOI":"10.1038\/nm1145","article-title":"Antibacterial resistance worldwide: Causes, challenges and responses","volume":"10","author":"Levy","year":"2004","journal-title":"Nat. Med."},{"key":"ref_21","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. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/nrmicro3380","article-title":"Molecular mechanisms of antibiotic resistance","volume":"13","author":"Blair","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Munita, J.M., and Arias, C.A. (2016). Mechanisms of Antibiotic Resistance. Microbiol. Spectr., 4.","DOI":"10.1128\/microbiolspec.VMBF-0016-2015"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1093\/jac\/dkg050","article-title":"The importance of efflux pumps in bacterial antibiotic resistance","volume":"51","author":"Webber","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Long, S., Sousa, E., Kijjoa, A., and Pinto, M.M.M. (2016). Marine Natural Products as Models to Circumvent Multidrug Resistance. Molecules, 21.","DOI":"10.3390\/molecules21070892"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1021\/np900177m","article-title":"Reversal of fluconazole resistance by sulfated sterols from the marine sponge Topsentia sp.","volume":"72","author":"Digirolamo","year":"2009","journal-title":"J. Nat. Prod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1836982","DOI":"10.1155\/2019\/1836982","article-title":"Brown and Red Seaweeds Serve as Potential Efflux Pump Inhibitors for Drug-Resistant Escherichia coli","volume":"2019","author":"Lu","year":"2019","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1021\/np500775e","article-title":"Enhancement of antibiotic activity against multidrug-resistant bacteria by the efflux pump inhibitor 3,4-dibromopyrrole-2,5-dione isolated from a Pseudoalteromonas sp.","volume":"78","author":"Whalen","year":"2015","journal-title":"J. Nat. Prod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"129","DOI":"10.4103\/ijmr.IJMR_2079_17","article-title":"Efflux pump inhibitors for bacterial pathogens: From bench to bedside","volume":"149","author":"Sharma","year":"2019","journal-title":"Indian J. Med. Res."},{"key":"ref_30","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_31","doi-asserted-by":"crossref","unstructured":"Kalia, V.C. (2018). Efflux Pump-Mediated Quorum Sensing: New Avenues for Modulation of Antimicrobial Resistance and Bacterial Virulence. Biotechnological Applications of Quorum Sensing Inhibitors, Springer.","DOI":"10.1007\/978-981-10-9026-4"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.3389\/fmicb.2019.01100","article-title":"Relationship Between Quorum Sensing and Secretion Systems","volume":"10","author":"Pena","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.tim.2004.11.007","article-title":"Sociomicrobiology: The connections between quorum sensing and biofilms","volume":"13","author":"Parsek","year":"2005","journal-title":"Trends Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8583","DOI":"10.1016\/j.tet.2013.07.078","article-title":"Bioactive meroditerpenes and indole alkaloids from the soil fungus Neosartorya fischeri (KUFC 6344), and the marine-derived fungi Neosartorya laciniosa (KUFC 7896) and Neosartorya tsunodae (KUFC 9213)","volume":"69","author":"Eamvijarn","year":"2013","journal-title":"Tetrahedron"},{"key":"ref_35","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_36","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_37","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_38","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_39","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/nature13205","article-title":"Structure of the AcrAB-TolC multidrug efflux pump","volume":"509","author":"Du","year":"2014","journal-title":"Nature"},{"key":"ref_40","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_41","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_42","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_43","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_44","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_45","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_46","doi-asserted-by":"crossref","first-page":"e00908-19","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_47","first-page":"157","article-title":"Chemical constituents, and their cytotoxicity, of the rare wood decaying fungus Xylaria humosa","volume":"9","author":"Sodngam","year":"2014","journal-title":"Nat. Prod. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4253","DOI":"10.3390\/toxins7104253","article-title":"Comparative Ochratoxin Toxicity: A Review of the Available Data","volume":"7","author":"Heussner","year":"2015","journal-title":"Toxins"},{"key":"ref_49","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_50","unstructured":"CLSI (2018). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, Clinical and Laboratory Standards Institute. [11th ed.]."},{"key":"ref_51","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_52","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_53","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_54","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 Crystallogr. D Biol. Crystallogr."},{"key":"ref_55","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_56","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_57","doi-asserted-by":"crossref","unstructured":"The UniProt Consortium (2017). UniProt: The universal protein knowledgebase. Nucleic Acids Res., 45, D158\u2013D169.","DOI":"10.1093\/nar\/gkw1099"},{"key":"ref_58","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_59","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_60","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\/19\/9\/475\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:51:03Z","timestamp":1760165463000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/19\/9\/475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,25]]},"references-count":60,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["md19090475"],"URL":"https:\/\/doi.org\/10.3390\/md19090475","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,25]]}}}