{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:54:40Z","timestamp":1791438880929,"version":"4.3.3"},"reference-count":40,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100013209","name":"Hellenic Foundation for Research and Innovation","doi-asserted-by":"publisher","award":["06057"],"award-info":[{"award-number":["06057"]}],"id":[{"id":"10.13039\/501100013209","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:p>\n                    Natural products represent an important source of bioactive compounds; however, their complexity often challenges conventional discovery approaches. In this study, an ethyl acetate extract of\n                    <jats:italic>Artemisia arborescens<\/jats:italic>\n                    (Vaill.) L. was investigated prior to any isolation using an integrated statistical spectroscopy\u2013driven dereplication strategy combining the HeteroCovariance Approach (HetCA), Statistical Total Correlation Spectroscopy (STOCSY),\n                    <jats:sup>1<\/jats:sup>\n                    H NMR, and LC\u2010HRMS\/MS. HetCA illustrated candidate features correlated with antileishmanial activity, predominantly associated with furofuran lignans. STOCSY facilitated metabolite annotation and distinction of structurally similar metabolites, enabling the identification of a novel lignan and a previously unreported compound in\n                    <jats:italic>A. arborescens<\/jats:italic>\n                    . Targeted isolation verified STOCSY\u2010guided annotations, while biological evaluation of the pure metabolites revealed that compounds\n                    <jats:bold>1<\/jats:bold>\n                    \u2013\n                    <jats:bold>3<\/jats:bold>\n                    exhibit moderate activity against\n                    <jats:italic>Leishmania<\/jats:italic>\n                    promastigotes, despite originating from a crude extract exhibiting negligible antileishmanial activity under the initial screening conditions. These findings demonstrate that HetCA can reveal bioactive compounds independently of extract\u2010level activity and highlight its potential as a robust tool for broadening natural product drug discovery beyond conventional bioactivity\u2010guided approaches.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70421","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T02:47:27Z","timestamp":1785984447000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HetCA\/STOCSY\u2010Guided Dereplication of\n                    <i>Artemisia arborescens<\/i>\n                    Reveals Furofuran Lignans with Antileishmanial Effects"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2516-5253","authenticated-orcid":false,"given":"Olga","family":"Karoutzou","sequence":"first","affiliation":[{"name":"Division of Pharmaceutical Chemistry Department of Pharmacy National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4937-0822","authenticated-orcid":false,"given":"Stavros","family":"Beteinakis","sequence":"additional","affiliation":[{"name":"Division of Pharmacognosy and Natural Products Chemistry Department of Pharmacy National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Koutsoni","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Laboratory Microbiology Department Hellenic Pasteur Institute  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4996-2879","authenticated-orcid":false,"given":"Despina","family":"Smirlis","sequence":"additional","affiliation":[{"name":"Molecular Parasitology Laboratory Microbiology Department Hellenic Pasteur Institute  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5620-0165","authenticated-orcid":false,"given":"Maria","family":"Halabalaki","sequence":"additional","affiliation":[{"name":"Division of Pharmacognosy and Natural Products Chemistry Department of Pharmacy National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandros Alexios","family":"Skaltsounis","sequence":"additional","affiliation":[{"name":"Division of Pharmacognosy and Natural Products Chemistry Department of Pharmacy National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5984-5169","authenticated-orcid":false,"given":"Emmanuel","family":"Mikros","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Chemistry Department of Pharmacy National and Kapodistrian University of Athens  Athens Greece"},{"name":"PharmaInformatics Unit \u201cATHENA\u201d Research and Innovation Center  Marousi Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2024.108752"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1657"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2015.08.001"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9NP00011A"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-00114-z"},{"key":"e_1_2_10_7_1","first-page":"136","article-title":"Current Approaches and Challenges for the Metabolite Profiling of Complex Natural Extracts","volume":"2015","author":"Wolfender J. 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