{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T05:01:54Z","timestamp":1780981314343,"version":"3.54.1"},"reference-count":42,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondecyt Regular","award":["1230414"],"award-info":[{"award-number":["1230414"]}]},{"name":"UDLA","award":["PIR202409"],"award-info":[{"award-number":["PIR202409"]}]},{"name":"FONDECYT","award":["1251871"],"award-info":[{"award-number":["1251871"]}]},{"name":"NLHPC","award":["CCSS210001"],"award-info":[{"award-number":["CCSS210001"]}]},{"DOI":"10.13039\/501100011875","name":"Ministry of Science, Technology and Innovation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100011875","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministry of Education"},{"name":"Ministry of Industry, Commerce and Tourism"},{"name":"Francisco Jos\u00e9 de Caldas Fund","award":["RC-FP44842-212-2018"],"award-info":[{"award-number":["RC-FP44842-212-2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>The aim of this research was to identify the wealth of secondary metabolites in the Chilean lichen Sticta caulescens, applying green chemistry approaches and comparing the following two extraction methods: (a) conventional maceration with methanol, and (b) microwave-assisted extraction (MAE) using ethyl lactate as a solvent. In addition, chemoinformatic and chemotaxonomic studies were conducted on S. caulescens and other species of the genus Sticta, which have been reported in previous studies. A UHPLC\/ESI-MS\/MS analysis allowed for the identification of 32 metabolites obtained from maceration and 33 from MAE, considering carbohydrates, aromatic compounds, acids, depsides, depsidones, dibenzofurans, lipids, anthraquinones, and triterpenes. Maceration using methanol yielded a slightly higher extract percentage than with ethyl lactate (6.3% versus 5.0%), while MAE extracted an almost identical spectrum of metabolites using ethyl lactate,\u2014though including one compound detected only under MAE conditions. This highlighted both the method efficiency and selectivity. This study also incorporates a comprehensive chemoinformatic and chemotaxonomic analysis of secondary metabolites across 12 Sticta species. A computational comparison (Morgan fingerprints, Jaccard similarity, hierarchical clustering, Murcko scaffolds) demonstrated that S. caulescens is one of the most chemically diverse species, closely related to S. cordillerana, and forming part of a major chemotaxonomic lineage, which is characterized by high scaffold richness and shared aromatic\/depsidone biosynthetic pathways.<\/jats:p>","DOI":"10.3390\/plants15111761","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T14:10:42Z","timestamp":1780668642000},"page":"1761","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phytochemical Profiling of Sticta caulescens De Not.: Green Extraction and Multiscale Chemotaxonomic Analysis"],"prefix":"10.3390","volume":"15","author":[{"given":"Nicol\u00e1s","family":"Cifuentes-Araya","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago 8320000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Valdivia","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago 8320000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0203-4891","authenticated-orcid":false,"given":"Mariano Walter","family":"Pertino","sequence":"additional","affiliation":[{"name":"Laboratorio de Qu\u00edmica de Productos Naturales, Instituto de Qu\u00edmica de Recursos Naturales, Universidad de Talca, Casilla 747, Talca 3460000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Marroqu\u00edn-Guerra","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias, Ingenier\u00eda e Innovaci\u00f3n, Universidad de Ibagu\u00e9, Carrera 22 Calle 67, Ibagu\u00e9 730002, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8993-9353","authenticated-orcid":false,"given":"Osvaldo","family":"Y\u00e1\u00f1ez","sequence":"additional","affiliation":[{"name":"Centro de Modelaci\u00f3n Ambiental y Din\u00e1mica de Sistemas (CEMADIS), Facultad de Ingenier\u00eda y Negocios, Universidad de Las Am\u00e9ricas, Santiago 7500975, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3312-1776","authenticated-orcid":false,"given":"Olimpo","family":"Garc\u00eda-Beltr\u00e1n","sequence":"additional","affiliation":[{"name":"Centro de Estudios e Investigaci\u00f3n en Salud y Sociedad (EISS), Universidad Bernardo O\u2019Higgins, General Gana 1702, Santiago 8370854, Chile"},{"name":"Co-Laboratorio de Investigaci\u00f3n en Bioeconom\u00eda Regional, Universidad de Ibagu\u00e9, Carrera 22 Calle 67, Ibagu\u00e9 730002, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Ardiles","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas, Facultad de Ciencias, Universidad Santo Tomas, Antofagasta 1240000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5246-1368","authenticated-orcid":false,"given":"Carlos","family":"Areche","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago 8320000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1079\/PGR200572","article-title":"Lichens\u2014A promising source of bioactive secondary metabolites","volume":"3","author":"Boustie","year":"2005","journal-title":"Plant Genet. Resour."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rankovi\u0107, B. (2019). Lichens as a Potential Source of Bioactive Secondary Metabolites. Lichen Secondary Metabolites, Springer.","DOI":"10.1007\/978-3-030-16814-8"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2307\/3242751","article-title":"Biological Role of Lichen Substances","volume":"89","author":"Lawrey","year":"1986","journal-title":"Bryologist"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s11101-010-9189-6","article-title":"Lichens as a potential natural source of bioactive compounds: A review","volume":"9","author":"Shukla","year":"2010","journal-title":"Phytochem. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1039\/c3np70064j","article-title":"UV-protectant metabolites from lichens and their symbiotic partners","volume":"30","author":"Nguyen","year":"2013","journal-title":"Nat. Prod. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/S0305-1978(99)00092-7","article-title":"Secondary metabolites in the genus Sticta (lichens)","volume":"28","author":"Piovano","year":"2000","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Farooq, S., Mir, S.A., Shah, M.A., and Manickavasagan, A. (2022). Extraction techniques. Plant Extracts: Applications in the Food Industry, Elsevier.","DOI":"10.1016\/B978-0-12-822475-5.00005-3"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1080\/19476337.2017.1411978","article-title":"Green technologies for the extraction of bioactive compounds in fruits and vegetables","volume":"16","author":"Soquetta","year":"2018","journal-title":"CyTA J. Food."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.trac.2015.04.013","article-title":"Ultrasound: A clean, green extraction technology","volume":"71","author":"Tiwari","year":"2015","journal-title":"TrAC Anal. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8615","DOI":"10.3390\/ijms13078615","article-title":"Green extraction of natural products: Concept and principles","volume":"13","author":"Chemat","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Calla-Quispe, E., Robles, J., Areche, C., and Sepulveda, B. (2020). Are Ionic Liquids Better Extracting Agents Than Toxic Volatile Organic Solvents? A Combination of Ionic Liquids, Microwave and LC\/MS\/MS, Applied to the Lichen Stereocaulon glareosum. Front. Chem., 8.","DOI":"10.3389\/fchem.2020.00450"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1051\/analusis:1999116","article-title":"Microwave assisted extraction of organic compounds","volume":"27","author":"Letellier","year":"1999","journal-title":"Analusis"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.lwt.2007.04.013","article-title":"Application of microwave-assisted extraction to the fast extraction of plant phenolic compounds","volume":"41","author":"Proestos","year":"2008","journal-title":"LWT Food Sci. Technol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15288","DOI":"10.1039\/C4CC06147K","article-title":"Limonene: A versatile chemical of the bioeconomy","volume":"50","author":"Ciriminna","year":"2014","journal-title":"Chem. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2174\/2213346103666151203203139","article-title":"Ethyl Lactate As a Green Solvent: A Promising Bio-compatible Media for Organic Synthesis","volume":"3","author":"Paul","year":"2016","journal-title":"Curr. Green Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chemat, F., and Aber Vian, M. (2014). Alternative solvents for natural products extraction. Green Chemistry and Sustainable Technology, Springer.","DOI":"10.1007\/978-3-662-43628-8"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Albornoz, L., Torres-Ben\u00edtez, A., Moreno-Palacios, M., Simirgiotis, M.J., Montoya-Serrano, S.A., Sepulveda, B., Stashenko, E., Garc\u00eda-Beltr\u00e1n, O., and Areche, C. (2022). Phylogenetic Studies and Metabolite Analysis of Sticta Species from Colombia and Chile by Ultra-High Performance Liquid Chromatography-High Resolution-Q-Orbitrap-Mass Spectrometry. Metabolites, 12.","DOI":"10.3390\/metabo12020156"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107184","DOI":"10.1016\/j.microc.2022.107184","article-title":"Sustainable extraction bioactive compounds procedures in medicinal plants based on the principles of green analytical chemistry: A review","volume":"175","author":"Carneiro","year":"2022","journal-title":"Microchem. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1080\/19476337.2022.2157492","article-title":"Recent insights into green extraction techniques as efficient methods for the extraction of bioactive components and essential oils from foods","volume":"21","author":"Majid","year":"2023","journal-title":"CyTA J. Food"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1021\/jf8026292","article-title":"Carotenoid extraction from plants using a novel, enviromentally friendly solvent","volume":"57","author":"Ishida","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.cej.2011.06.077","article-title":"Liquid-liquid equilibria for separation of tocopherol from olive oil using ethyl lactate","volume":"172","author":"Vicente","year":"2011","journal-title":"Chem. Eng. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.supflu.2007.12.007","article-title":"Three-component phase behavior of the sclareol-ethyl lactate-carbon dioxide system for GAS applications","volume":"45","author":"Tombokan","year":"2008","journal-title":"J. Supercrit. Fluids"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"117447","DOI":"10.1016\/j.seppur.2020.117447","article-title":"Novel ethyl lactate based ATPS for the purification of rutin and quercetin","volume":"252","author":"Velho","year":"2020","journal-title":"Sep. Purif. Technol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.scp.2016.07.003","article-title":"Ethyl lactate as a potential green solvent to extract hydrophilic (polar) and lipophilic (non-polar) phytonutrients simultaneously from fruit and vegetable by-products","volume":"4","author":"Kua","year":"2016","journal-title":"Sustain. Chem. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.fluid.2018.01.016","article-title":"Partitioning of amino acids in the novel biphasic systems based on environmentally friendly ethyl lactate","volume":"462","author":"Kamalanathan","year":"2018","journal-title":"Fluid Phase Equilibria"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Rajkowska, K., Simi\u0144ska, D., and Kunicka-Styczy\u0144ska, A. (2022). Bioactivities and Microbial Quality of Lycium Fruits (Goji) Extracts Derived by Various Solvents and Green Extraction Methods. Molecules, 27.","DOI":"10.3390\/molecules27227856"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1080\/14786419.2021.1956922","article-title":"Green ultrasound-assisted extraction of lichen substances from Hypotrachyna cirrhata. Ethyl lactate, a better extracting agent tan metanol toxic organic solvent?","volume":"37","author":"Sepulveda","year":"2023","journal-title":"Nat. Prod. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1080\/14786419.2022.2116703","article-title":"A sustainable application for the extraction of lichen metabolites from Usnea cornuta: Nontargeted metabolomics and antioxidant activity","volume":"37","author":"Sepulveda","year":"2023","journal-title":"Nat. Prod. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1039\/c1gc15523g","article-title":"Ethyl lactate as a solvent: Properties, applications and production processes-a review","volume":"13","author":"Pereira","year":"2011","journal-title":"Green Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s13225-013-0230-0","article-title":"Molecular phylogeny of the genus Sticta (lichenized Ascomycota: Lobariaceae) in Colombia","volume":"64","author":"Moncada","year":"2014","journal-title":"Fungal Divers."},{"key":"ref_31","first-page":"74","article-title":"Macroevolution of Specificity in Cyanolichens of the Genus Peltigera Section Polydactylon (Lecanoromycetes, Ascomycota)","volume":"66","author":"Magain","year":"2017","journal-title":"Syst. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"18047","DOI":"10.3390\/molecules201018047","article-title":"Metabolic Profiling of Alpine and Ecuadorian Lichens","volume":"20","author":"Mittermeier","year":"2015","journal-title":"Molecules"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1039\/C9NP00045C","article-title":"Biosynthetic gene clusters and the evolution of fungal chemodiversity","volume":"37","author":"Rokas","year":"2020","journal-title":"Nat. Prod. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Paukov, A., Teptina, A., Morozova, M., Kruglova, E., Favero-Longo, S.E., Bishop, C., and Rajakaruna, N. (2019). The Effects of Edaphic and Climatic Factors on Secondary Lichen Chemistry: A Case Study Using Saxicolous Lichens. Diversity, 11.","DOI":"10.3390\/d11060094"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ure\u00f1a-Vacas, I., Gonz\u00e1lez-Burgos, E., Divakar, P.K., and G\u00f3mez-Serranillos, M.P. (2023). Lichen Depsides and Tridepsides: Progress in Pharmacological Approaches. J. Fungi, 9.","DOI":"10.3390\/jof9010116"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1080\/12298093.2024.2416736","article-title":"A Comprehensive Review of the Diversity of Fungal Secondary Metabolites and Their Emerging Applications in Healthcare and Environment","volume":"52","author":"Wadhwa","year":"2024","journal-title":"Mycobiology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1021\/jm9602928","article-title":"The Properties of Known Drugs. 1. Molecular Frameworks","volume":"39","author":"Bemis","year":"1996","journal-title":"J. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Singh, G., Armaleo, D., Dal Grande, F., and Schmitt, I. (2021). Depside and Depsidone Synthesis in Lichenized Fungi Comes into Focus through a Genome-Wide Comparison of the Olivetoric Acid and Physodic Acid Chemotypes of Pseudevernia furfuracea. Biomolecules, 11.","DOI":"10.1101\/2021.09.07.459332"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"evad002","DOI":"10.1093\/gbe\/evad002","article-title":"Metagenomics Shines Light on the Evolution of \u201cSunscreen\u201d Pigment Metabolism in the Teloschistales (Lichen-Forming Ascomycota)","volume":"15","author":"Llewellyn","year":"2023","journal-title":"Genome Biol. Evol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1021\/ci9800211","article-title":"Chemical Similarity Searching","volume":"38","author":"Willett","year":"1998","journal-title":"J. Chem. Inf. Comput. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13321-015-0069-3","article-title":"Why Is Tanimoto Index an Appropriate Choice for Fingerprint-Based Similarity Calculations?","volume":"7","author":"Bajusz","year":"2015","journal-title":"J. Cheminformatics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1111\/j.1558-5646.1985.tb00420.x","article-title":"Confidence Limits on Phylogenies: An Approach Using the Bootstrap","volume":"39","author":"Felsenstein","year":"1985","journal-title":"Evolution"}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/15\/11\/1761\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:42:35Z","timestamp":1780980155000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/15\/11\/1761"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,5]]},"references-count":42,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["plants15111761"],"URL":"https:\/\/doi.org\/10.3390\/plants15111761","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,5]]}}}