{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T13:11:35Z","timestamp":1767964295167,"version":"3.49.0"},"reference-count":28,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,6]],"date-time":"2021-03-06T00:00:00Z","timestamp":1614988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["729.004.026"],"award-info":[{"award-number":["729.004.026"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/50216-0"],"award-info":[{"award-number":["2017\/50216-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In order to replace the huge amounts of copper salts used in citrus orchards, alternatives have been sought in the form of organic compounds of natural origin with activity against the causative agent of citrus canker, the phytopathogen Xanthomonas citri subsp. Citri. We synthesized a series of 4-alkoxy-1,2-benzene diols (alkyl-BDOs) using 1,2,4-benzenetriol (BTO) as a starting material through a three-step synthesis route and evaluated their suitability as antibacterial compounds. Our results show that alkyl ethers derived from 1,2,4-benzenetriol have bactericidal activity against X. citri, disrupting the bacterial cell membrane within 15 min. Alkyl-BDOs were also shown to remain active against the bacteria while in solution, and presented low toxicity to (human) MRC-5 cells. Therefore, we have demonstrated that 1,2,4-benzenetriol\u2014a molecule that can be obtained from agricultural residues\u2014is an adequate precursor for the synthesis of new compounds with activity against X. citri.<\/jats:p>","DOI":"10.3390\/molecules26051436","type":"journal-article","created":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T21:52:15Z","timestamp":1615153935000},"page":"1436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Benzenetriol-Derived Compounds against Citrus Canker"],"prefix":"10.3390","volume":"26","author":[{"given":"L\u00facia Bonci","family":"Cavalca","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747 AG Groningen, The Netherlands"},{"name":"Department of Chemical Engineering (ENTEG), University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ciaran W.","family":"Lahive","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering (ENTEG), University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fleur","family":"Gijsbers","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747 AG Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando Rog\u00e9rio","family":"Pavan","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9439-9168","authenticated-orcid":false,"given":"Dirk-Jan","family":"Scheffers","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747 AG Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2254-2500","authenticated-orcid":false,"given":"Peter J.","family":"Deuss","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering (ENTEG), University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gottwald, T.R., Graham, J.H., Alfred, L., and Schubert, T.S. (2002). Citrus Canker: The Pathogen and Its Impact. Plant Health Progress.","DOI":"10.1094\/PHP-2002-0812-01-RV"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13593-018-0503-9","article-title":"Thirteen decades of antimicrobial copper compounds applied in agriculture. A review","volume":"38","author":"Lamichhane","year":"2018","journal-title":"Agron. Sustain. Dev."},{"key":"ref_3","first-page":"390","article-title":"Antibacterial activity of alkyl gallates is a combination of direct targeting of FtsZ and permeabilization of bacterial membranes","volume":"6","author":"Polaquini","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Nazar\u00e9, A.C., Polaquini, C.R., Cavalca, L.B., Anselmo, D., Saiki, M., Monteiro, D., Zielinska, A., Rahal, P., Gomes, E., and Scheffers, D.-J. (2018). Design of antibacterial agents: Alkyl dihydroxybenzoates against xanthomonas citri subsp. citri. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19103050"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1128\/JB.01442-12","article-title":"Antibacterial activity of alkyl gallates against Xanthomonas citri subsp. citri","volume":"195","author":"Silva","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0008-6215(93)80027-C","article-title":"Hydrothermal formation of 1,2,4-benzenetriol from 5-hydroxymethyl-2-furaldehyde and d-fructose","volume":"242","author":"Luijkx","year":"1993","journal-title":"Carbohydr. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3419","DOI":"10.1021\/acssuschemeng.7b03648","article-title":"Lewis Acid Catalyzed Conversion of 5-Hydroxymethylfurfural to 1,2,4-Benzenetriol, an Overlooked Biobased Compound","volume":"6","author":"Kumalaputri","year":"2018","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4304","DOI":"10.1002\/cssc.201901115","article-title":"High-Yield 5-Hydroxymethylfurfural Synthesis from Crude Sugar Beet Juice in a Biphasic Microreactor","volume":"12","author":"Guo","year":"2019","journal-title":"ChemSusChem"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4273","DOI":"10.1039\/D0CS00041H","article-title":"Recent catalytic routes for the preparation and the upgrading of biomass derived furfural and 5-hydroxymethylfurfural","volume":"49","author":"Xu","year":"2020","journal-title":"Chem. Soc. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.4155\/fmc-2016-0031","article-title":"Characterization of chemical features of potent myeloperoxidase inhibitors","volume":"8","author":"Soubhye","year":"2016","journal-title":"Future Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5161","DOI":"10.1021\/jo300565s","article-title":"Total Synthesis of Thelephantin O, Vialinin A\/Terrestrin A, and Terrestrins B\u2013D","volume":"77","author":"Fujiwara","year":"2012","journal-title":"J. Org. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1021\/acs.oprd.8b00303","article-title":"Biobased Chemicals: 1,2,4-Benzenetriol, Selective Deuteration and Dimerization to Bifunctional Aromatic Compounds","volume":"22","author":"Randolph","year":"2018","journal-title":"Org. Process Res. Dev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1080\/00304949609356553","article-title":"A simple one-pot preparation of 4-alkoxy-and 4-alkylthio-catechols and o-benzoquinones","volume":"28","author":"Cooksey","year":"1996","journal-title":"Org. Prep. Proced. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1002\/qsar.19960150606","article-title":"Tyrosinase-Mediated Cytotoxicity of 4-Substituted Phenols: Use of QSAR to Forecast Reactivities of Thiols towards the Derived ortho -Quinones","volume":"15","author":"Cooksey","year":"1996","journal-title":"Quant. Struct. Relatsh."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1248\/cpb.39.1736","article-title":"Quantitative Structure-Activity Relationship of Catechol Derivatives Inhibiting 5-Lipoxygenase","volume":"39","author":"Naito","year":"1991","journal-title":"Chem. Pharm. Bull. (Tokyo)"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3993","DOI":"10.1016\/j.bmcl.2003.08.057","article-title":"Rational design of antimicrobial agents: Antifungal activity of alk(en)yl dihydroxybenzoates and dihydroxyphenyl alkanoates","volume":"13","author":"Nihei","year":"2003","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_17","first-page":"IDRT","article-title":"Eugenol Provokes ROS-Mediated Membrane Damage-Associated Antibacterial Activity against Clinically Isolated Multidrug-Resistant Staphylococcus aureus Strains","volume":"9","author":"Das","year":"2016","journal-title":"Infect. Dis. Res. Treat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.1080\/10408398.2019.1675585","article-title":"The antibacterial properties of phenolic isomers, carvacrol and thymol","volume":"60","author":"Kachur","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.ejmech.2017.11.095","article-title":"An overview of natural antimicrobials role in food","volume":"143","author":"Pisoschi","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"68","DOI":"10.4315\/0362-028X.JFP-17-214","article-title":"Bacteriostatic effect of quercetin as an antibiotic alternative in vivo and its antibacterial mechanism in vitro","volume":"81","author":"Wang","year":"2018","journal-title":"J. Food Prot."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wu, Y., Bai, J., Zhong, K., Huang, Y., Qi, H., Jiang, Y., and Gao, H. (2016). Antibacterial activity and membrane-disruptive mechanism of 3-p-trans-coumaroyl-2-hydroxyquinic acid, a novel phenolic compound from pine needles of Cedrus deodara, against Staphylococcus aureus. Molecules, 21.","DOI":"10.3390\/molecules21081084"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cavalca, L.B., Zamuner, C.F.C., Saldanha, L.L., Polaquini, C.R., Regasini, L.O., Behlau, F., and Ferreira, H. (2020). Hexyl gallate for the control of citrus canker caused by Xanthomonas citri subsp citri. Microbiologyopen.","DOI":"10.1002\/mbo3.1104"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1007\/s00203-018-1502-6","article-title":"Antibacterial activity of monoacetylated alkyl gallates against Xanthomonas citri subsp. citri","volume":"200","author":"Savietto","year":"2018","journal-title":"Arch. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1094\/PDIS-12-19-2673-RE","article-title":"Spray volume and rate based on the tree row volume for a sustainable use of copper in the control of citrus canker","volume":"105","author":"Behlau","year":"2021","journal-title":"Plant Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.bioorg.2019.02.010","article-title":"Novel lawsone-containing ruthenium(II) complexes: Synthesis, characterization and anticancer activity on 2D and 3D spheroid models of prostate cancer cells","volume":"85","author":"Santos","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.fct.2017.04.033","article-title":"Evaluation of cytotoxic, apoptotic, mutagenic, and chemopreventive activities of semi-synthetic esters of gallic acid","volume":"105","author":"Silva","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/417459a","article-title":"Comparison of the genomes of two Xanthomonas pathogens with differing host specificities","volume":"417","author":"Ferro","year":"2002","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1016\/j.ejmech.2010.01.028","article-title":"Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide\/hydrazones: Anti-Mycobacterium tuberculosis activity and cytotoxicity","volume":"45","author":"Pavan","year":"2010","journal-title":"Eur. J. Med. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/5\/1436\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:34:11Z","timestamp":1760160851000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/5\/1436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,6]]},"references-count":28,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["molecules26051436"],"URL":"https:\/\/doi.org\/10.3390\/molecules26051436","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,6]]}}}