{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T11:16:28Z","timestamp":1778325388818,"version":"3.51.4"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T00:00:00Z","timestamp":1590019200000},"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":["PTDC\/SAU-PUB\/28736\/2017 (reference POCI-01-0145-FEDER-028736)"],"award-info":[{"award-number":["PTDC\/SAU-PUB\/28736\/2017 (reference POCI-01-0145-FEDER-028736)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"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"],"award-info":[{"award-number":["UIDB\/04423\/2020, UIDP\/04423\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A series of thirteen xanthones 3\u201315 was prepared based on substitutional (appendage) diversity reactions. The series was structurally characterized based on their spectral data and HRMS, and the structures of xanthone derivatives 1, 7, and 8 were determined by single-crystal X-ray diffraction. This series, along with an in-house series of aminated xanthones 16\u201333, was tested for in-vitro antimicrobial activity against seven bacterial (including two multidrug-resistant) strains and five fungal strains. 1-(Dibromomethyl)-3,4-dimethoxy-9H-xanthen-9-one (7) and 1-(dibromomethyl)-3,4,6-trimethoxy-9H-xanthen-9-one (8) exhibited antibacterial activity against all tested strains. In addition, 3,4-dihydroxy-1-methyl-9H-xanthen-9-one (3) revealed a potent inhibitory effect on the growth of dermatophyte clinical strains (T. rubrum FF5, M. canis FF1 and E. floccosum FF9), with a MIC of 16 \u00b5g\/mL for all the tested strains. Compounds 3 and 26 showed a potent inhibitory effect on two C. albicans virulence factors: germ tube and biofilm formation.<\/jats:p>","DOI":"10.3390\/molecules25102405","type":"journal-article","created":{"date-parts":[[2020,5,22]],"date-time":"2020-05-22T10:18:18Z","timestamp":1590142698000},"page":"2405","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Synthesis of a Small Library of Nature-Inspired Xanthones and Study of Their Antimicrobial Activity"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4077-6060","authenticated-orcid":false,"given":"Diana I. S. P.","family":"Resende","sequence":"first","affiliation":[{"name":"CIIMAR - Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental, Terminal de Cruzeiros do Porto de Leix\u00f5es, 4450-208 Matosinhos, Portugal"},{"name":"Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Patr\u00edcia","family":"Pereira-Terra","sequence":"additional","affiliation":[{"name":"CIIMAR - Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental, Terminal de Cruzeiros do Porto de Leix\u00f5es, 4450-208 Matosinhos, Portugal"},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Joana","family":"Moreira","sequence":"additional","affiliation":[{"name":"CIIMAR - Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental, Terminal de Cruzeiros do Porto de Leix\u00f5es, 4450-208 Matosinhos, Portugal"},{"name":"Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Joana","family":"Freitas-Silva","sequence":"additional","affiliation":[{"name":"CIIMAR - Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental, Terminal de Cruzeiros do Porto de Leix\u00f5es, 4450-208 Matosinhos, Portugal"},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Agostinho","family":"Lemos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Lu\u00eds","family":"Gales","sequence":"additional","affiliation":[{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"IBMC \u2013 Instituto de Biologia Molecular e Celular Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"given":"Eug\u00e9nia","family":"Pinto","sequence":"additional","affiliation":[{"name":"CIIMAR - Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental, Terminal de Cruzeiros do Porto de Leix\u00f5es, 4450-208 Matosinhos, Portugal"},{"name":"Laborat\u00f3rio de Microbiologia, Departamento de Ci\u00eancias Biol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Maria Em\u00edlia","family":"de Sousa","sequence":"additional","affiliation":[{"name":"CIIMAR - Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental, Terminal de Cruzeiros do Porto de Leix\u00f5es, 4450-208 Matosinhos, Portugal"},{"name":"Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Paulo Martins","family":"da Costa","sequence":"additional","affiliation":[{"name":"CIIMAR - Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental, Terminal de Cruzeiros do Porto de Leix\u00f5es, 4450-208 Matosinhos, Portugal"},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Madalena M. M.","family":"Pinto","sequence":"additional","affiliation":[{"name":"CIIMAR - Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental, Terminal de Cruzeiros do Porto de Leix\u00f5es, 4450-208 Matosinhos, Portugal"},{"name":"Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Loureiro, D.R.P., Soares, J.X., Costa, J.C., Magalh\u00e3es, \u00c1.F., Azevedo, C.M.G., Pinto, M.M.M., and Afonso, C.M.M. (2019). Structures, Activities and Drug-Likeness of Anti-Infective Xanthone Derivatives Isolated from the Marine Environment: A Review. Molecules, 24.","DOI":"10.3390\/molecules24020243"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0168305","article-title":"Norlichexanthone Reduces Virulence Gene Expression and Biofilm Formation in Staphylococcus aureus","volume":"11","author":"Baldry","year":"2016","journal-title":"PLoS ONE"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1021\/np020518b","article-title":"Two New Xanthone Derivatives from the Algicolous Marine Fungus Wardomyces anomalus","volume":"66","author":"Klemke","year":"2003","journal-title":"J. Nat. Prod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1055\/s-0029-1186047","article-title":"The Bioactive Metabolites of the Mangrove Endophytic Fungus Talaromyces sp. ZH-154 Isolated from Kandelia candel (L.) Druce","volume":"76","author":"Liu","year":"2010","journal-title":"Planta Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1590\/S0102-695X2011005000222","article-title":"Evaluating methods for the isolation of marine-derived fungal strains and production of bioactive secondary metabolites","volume":"22","author":"Kossuga","year":"2012","journal-title":"Rev. Bras. De Farmacogn."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Li, H.-L., Li, X.-M., Liu, H., Meng, L.-H., and Wang, B.-G. (2016). Two New Diphenylketones and a New Xanthone from Talaromyces islandicus EN-501, an Endophytic Fungus Derived from the Marine Red Alga Laurencia okamurai. Mar. Drugs, 14.","DOI":"10.3390\/md14120223"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4492","DOI":"10.3390\/md13074492","article-title":"Identification and Bioactivity of Compounds from the Mangrove Endophytic Fungus Alternaria sp.","volume":"13","author":"Wang","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1002\/mrc.2293","article-title":"Structure elucidation of two new xanthone derivatives from the marine fungus Penicillium sp. (ZZF 32#) from the South China Sea","volume":"46","author":"Shao","year":"2008","journal-title":"Magn. Reson. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3601","DOI":"10.3390\/md11103601","article-title":"Advances in the Study of the Structures and Bioactivities of Metabolites Isolated from Mangrove-Derived Fungi in the South China Sea","volume":"11","author":"Wang","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1016\/j.bmcl.2015.03.057","article-title":"Polybrominated diphenyl ethers with potent and broad spectrum antimicrobial activity from the marine sponge Dysidea","volume":"25","author":"Sun","year":"2015","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.2174\/092986705774370736","article-title":"Synthesis of Xanthones: An Overview","volume":"12","author":"Sousa","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.bcp.2011.10.004","article-title":"Dual inhibitors of P-glycoprotein and tumor cell growth: (Re)discovering thioxanthones","volume":"83","author":"Palmeira","year":"2012","journal-title":"Biochem. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Martins, E., Silva, V., Lemos, A., Palmeira, A., Puthongking, P., Sousa, E., Rocha-Pereira, C., Ghanem, C.I., Carmo, H., and Remi\u00e3o, F. (2019). Newly Synthesized Oxygenated Xanthones as Potential P-Glycoprotein Activators: In Vitro, Ex Vivo, and In Silico Studies. Molecules, 24.","DOI":"10.3390\/molecules24040707"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Barbosa, J., Lima, R.T., Sousa, D., Gomes, A.S., Palmeira, A., Seca, H., Choosang, K., Pakkong, P., Bousbaa, H., and Pinto, M.M. (2016). Screening a Small Library of Xanthones for Antitumor Activity and Identification of a Hit Compound which Induces Apoptosis. Molecules, 21.","DOI":"10.3390\/molecules21010081"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1007\/s00204-014-1333-4","article-title":"P-glycoprotein induction in Caco-2 cells by newly synthetized thioxanthones prevents paraquat cytotoxicity","volume":"89","author":"Silva","year":"2015","journal-title":"Arch. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1089\/mdr.2014.0162","article-title":"Synergistic Effects Between Thioxanthones and Oxacillin Against Methicillin-Resistant Staphylococcus aureus","volume":"21","author":"Bessa","year":"2015","journal-title":"Microb. Drug Resist."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1007\/s00204-014-1193-y","article-title":"Induction and activation of P-glycoprotein by dihydroxylated xanthones protect against the cytotoxicity of the P-glycoprotein substrate paraquat","volume":"88","author":"Silva","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1007\/s00044-020-02544-1","article-title":"Oxygenated xanthones as P-glycoprotein modulators at the intestinal barrier: In vitro and docking studies","volume":"29","author":"Silva","year":"2020","journal-title":"Med. Chem. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Resende, D., Pereira-Terra, P., In\u00e1cio, \u00c2., Costa, P., Pinto, E., Sousa, E., and Pinto, M. (2018). Lichen Xanthones as Models for New Antifungal Agents. Molecules, 23.","DOI":"10.3390\/molecules23102617"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.canlet.2019.01.014","article-title":"New inhibitor of the TAp73 interaction with MDM2 and mutant p53 with promising antitumor activity against neuroblastoma","volume":"446","author":"Gomes","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1081\/SCC-120003625","article-title":"Synthesis of 3-Bromo Derivatives of Flavones","volume":"32","author":"Rho","year":"2002","journal-title":"Synth. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lemos, A., Gomes, A.S., Loureiro, J.B., Brand\u00e3o, P., Palmeira, A., Pinto, M.M.M., Saraiva, L., and Sousa, M.E. (2019). Synthesis, Biological Evaluation, and In Silico Studies of Novel Aminated Xanthones as Potential p53-Activating Agents. Molecules, 24.","DOI":"10.3390\/molecules24101975"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1021\/ol0340078","article-title":"Facile Oxidation of Aldehydes to Acids and Esters with Oxone","volume":"5","author":"Travis","year":"2003","journal-title":"Org. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.2174\/092986705774370727","article-title":"Xanthones-A Structural Perspective","volume":"12","author":"Gales","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1107\/S0021889812029111","article-title":"WinGX and ORTEP for Windows: An update","volume":"45","author":"Farrugia","year":"2012","journal-title":"J. Appl. Cryst."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15012","DOI":"10.1038\/npjbiofilms.2015.12","article-title":"A novel small molecule inhibitor of Candida albicans biofilm formation, filamentation and virulence with low potential for the development of resistance","volume":"1","author":"Pierce","year":"2015","journal-title":"npj Biofilms Microbiomes"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"17570","DOI":"10.1038\/s41598-018-35530-0","article-title":"Antifungal and anti-biofilm activity of the first cryptic antimicrobial peptide from an archaeal protein against Candida spp. clinical isolates","volume":"8","author":"Roscetto","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1055\/s-0034-1382827","article-title":"Uncommon Chlorinated Xanthone and Other Antibacterial Compounds from the Lichen Cladonia incrassata","volume":"80","author":"Dieu","year":"2014","journal-title":"Planta Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1039\/b110543b","article-title":"Lichens as a potential source of pesticides","volume":"12","author":"Dayan","year":"2001","journal-title":"Pestic. Outlook"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1107\/S0108767307043930","article-title":"A short history of SHELX","volume":"64","author":"Sheldrick","year":"2008","journal-title":"Acta Crystallogr. Sect. A: Found. Crystallogr."},{"key":"ref_31","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_32","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_33","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_34","unstructured":"Clinical and Laboratory Standards Institute (2015). Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, CLSI. [Approved Standard-10th ed.]. Document M07-A10."},{"key":"ref_35","unstructured":"Clinical and Laboratory Standards Institute (2008). Reference method for broth dilution antifungal susceptibility testing of yeasts, CLSI. [Approved Standard\u20143rd ed.]. Document M27-A3."},{"key":"ref_36","unstructured":"Clinical and Laboratory Standards Institute (2008). Reference method for broth dilution antifungal susceptibility testing of filamentous fungi, CLSI. [Approved Standard\u20142nd ed.]. Document M38-A2."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jac\/dkg301","article-title":"Synergy, antagonism, and what the chequerboard puts between them","volume":"52","author":"Odds","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lopes, G., Pinto, E., Andrade, P.B., and Valent\u00e3o, P. (2013). Antifungal Activity of Phlorotannins against Dermatophytes and Yeasts: Approaches to the Mechanism of Action and Influence on Candida albicans Virulence Factor. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072203"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"681","DOI":"10.3109\/13693780802549594","article-title":"Biofilms of non-Candida albicans Candida species: Quantification, structure and matrix composition","volume":"47","author":"Silva","year":"2009","journal-title":"Med. Mycol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/10\/2405\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:31:19Z","timestamp":1760175079000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/10\/2405"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,21]]},"references-count":39,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["molecules25102405"],"URL":"https:\/\/doi.org\/10.3390\/molecules25102405","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,21]]}}}