{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:18:11Z","timestamp":1790615891293,"version":"4.1.0"},"reference-count":43,"publisher":"American Chemical Society (ACS)","issue":"5","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Root extracts of Cryptolepis decidua are used in the traditional medicine of South-West Africa to treat various conditions. Here, we report the potent cytotoxic activity of a methanol root extract against a human adenocarcinomic cell line, which prompted us to establish a comprehensive metabolite profile. Overall, six previously undescribed compounds were isolated from this extract by a combination of open-column chromatography (CC), centrifugal partition chromatography (CPC), and preparative HPLC. They include two sarmentogenin-type cardenolides (2 and 3), an androstane lactone (5), two dinormonoterpenoid diglucosides, dinosides A and B (9 and 10), and a quinic acid derivative (12). In addition, six previously reported constituents were identified (1, 4, 6\u20138, 11). The structures of the isolates were elucidated using HPLC-MS2\/3, HRESIMS, and NMR spectroscopy. Feature-based molecular networking was used to map a comprehensive metabolite profile. The cytotoxic activity of the methanol extract was evaluated by WST-1 cell-viability assays, apoptosis\/necrosis tests, and cell-cycle analyses. Cardenolides 1\u20133 were identified as the primary cytotoxic agents, exhibiting IC50 values of 0.25 \u03bcM (1), 2.20 \u03bcM (2), and 0.28 \u03bcM (3) in A549 human lung epithelial cancer cells, and 0.41 \u03bcM (1), 2.31 \u03bcM (2), and 0.39 \u03bcM (3) against peripheral blood mononuclear cells (PBMCs).<\/jats:p>","DOI":"10.1021\/acs.jnatprod.6c00033","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T13:48:08Z","timestamp":1777038488000},"page":"1462-1477","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive\nMetabolite Profile and Cytotoxic Constituents\nof\n                    <i>Cryptolepis decidua<\/i>"],"prefix":"10.1021","volume":"89","author":[{"given":"Tobias","family":"Blank","sequence":"first","affiliation":[{"name":"University of Basel , , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie","family":"Puth","sequence":"additional","affiliation":[{"name":"University of Freiburg , , ,","place":["Freiburg, Germany, 79106"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annikka","family":"Kurz","sequence":"additional","affiliation":[{"name":"University of Freiburg , , ,","place":["Freiburg, Germany, 79106"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Benka","sequence":"additional","affiliation":[{"name":"University of Freiburg , , ,","place":["Freiburg, Germany, 79104"]},{"name":"University of Freiburg , , ,","place":["Freiburg, Germany, 79104"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malik","family":"Rakhmanov","sequence":"additional","affiliation":[{"name":"University of Basel , , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwanette","family":"Du Preez-Bruwer","sequence":"additional","affiliation":[{"name":"University of Namibia , , 340 Mandume Ndemufayo Avenue, Pioneers Park , ,","place":["Windhoek, Namibia, 13301"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davis","family":"Mumbengegwi","sequence":"additional","affiliation":[{"name":"University of Namibia , , 340 Mandume Ndemufayo Avenue, Pioneers Park , ,","place":["Windhoek, Namibia, 13301"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar A.","family":"Plattner","sequence":"additional","affiliation":[{"name":"University of Freiburg , , ,","place":["Freiburg, Germany, 79104"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Kammerer","sequence":"additional","affiliation":[{"name":"University of Freiburg , , ,","place":["Freiburg, Germany, 79104"]},{"name":"University of Freiburg , , ,","place":["Freiburg, Germany, 79104"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Huber","sequence":"additional","affiliation":[{"name":"University of Freiburg , , ,","place":["Freiburg, Germany, 79106"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5863-7248","authenticated-orcid":true,"given":"Robin","family":"Teufel","sequence":"additional","affiliation":[{"name":"University of Basel , , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5962-6516","authenticated-orcid":true,"given":"Olivier","family":"Potterat","sequence":"additional","affiliation":[{"name":"University of Basel , , ,","place":["Basel, Switzerland, 4056"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker M.","family":"Lu\u0308th","sequence":"additional","affiliation":[{"name":"University of Freiburg , , ,","place":["Freiburg, Germany, 79106"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"2026092812293749600_cit1","unstructured":"WFO.\n          \n          World Flora Online: Cryptolepis; 2025. https:\/\/worldfloraonline.org\/taxon\/wfo-4000009895. accessed 12 January 2026."},{"key":"2026092812293749600_cit2","doi-asserted-by":"publisher","first-page":"356","DOI":"10.21608\/aps.2024.278530.1165","article-title":"Leveraging the\ncytotoxic attributes of Apocynaceae: current status and opportunities","volume":"8","author":"Helmy","year":"2024","journal-title":"Arch. Pharm. Sci. Ain Shams Univ."},{"key":"2026092812293749600_cit3","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.fitote.2016.04.023","article-title":"Cardenolides from the Apocynaceae family and their anticancer activity","volume":"112","author":"Wen","year":"2016","journal-title":"Fitoterapia"},{"key":"2026092812293749600_cit4","doi-asserted-by":"publisher","first-page":"3026370","DOI":"10.1155\/2017\/3026370","article-title":"Phytochemical and\npharmacological\nreview of Cryptolepis sanguinolenta (Lindl.) Schlechter","volume":"2017","author":"Osafo","year":"2017","journal-title":"Adv. Pharmacol. Sci."},{"key":"2026092812293749600_cit5","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1021\/acs.jnatprod.4c01257","article-title":"Cytotoxic and noncytotoxic\nsteroidal constituents\nof Cryptolepis dubia","volume":"88","author":"Ren","year":"2025","journal-title":"J. Nat.\nProd."},{"key":"2026092812293749600_cit6","first-page":"103","article-title":"Cryptolepis buchanani Roem. Schult.,\na new source of sarmentogenin","volume":"1","author":"Shah","year":"1981","journal-title":"J. Nepal Chem.\nSoc."},{"key":"2026092812293749600_cit7","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1016\/0031-9422(89)80209-2","article-title":"Cryptosin,\na cardenolide from the leaves of Cryptolepis buchanani","volume":"28","author":"Venkateswara","year":"1989","journal-title":"Phytochemistry"},{"key":"2026092812293749600_cit8","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/S0305-1978(02)00075-3","article-title":"Chemotaxonomic analysis\nof the genus Cryptolepis","volume":"31","author":"Paulo","year":"2003","journal-title":"Biochem.\nSyst. Ecol."},{"key":"2026092812293749600_cit9","volume-title":"Heil-, Gift-\nund essbare Pflanzen in Namibia","author":"von Koenen","year":"1996"},{"key":"2026092812293749600_cit10","doi-asserted-by":"publisher","first-page":"112683","DOI":"10.1016\/j.jep.2020.112683","article-title":"Immunomodulatory effects of some\nNamibian plants traditionally used for treating inflammatory diseases","volume":"254","author":"Du Preez","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"2026092812293749600_cit11","doi-asserted-by":"publisher","first-page":"2351","DOI":"10.1016\/S0031-9422(00)84717-2","article-title":"Cardenolide glycosides of Strophanthus divaricatus","volume":"26","author":"Chen","year":"1987","journal-title":"Phytochemistry"},{"key":"2026092812293749600_cit12","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1016\/0031-9422(91)80023-T","article-title":"Cardenolides\nin the regenerated plants obtained from Strophanthus divaricatus calli","volume":"34","author":"Kawaguchi","year":"1993","journal-title":"Phytochemistry"},{"key":"2026092812293749600_cit13","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1021\/np068030o","article-title":"Bioactive\npregnanes from Nerium oleander","volume":"70","author":"Bai","year":"2007","journal-title":"J. Nat. 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Rep."},{"key":"2026092812293749600_cit17","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.jpba.2008.02.013","article-title":"Characterization\nof phenolic compounds in the Chinese herbal drug Artemisia annua by liquid chromatography coupled to electrospray ionization\nmass spectrometry","volume":"47","author":"Han","year":"2008","journal-title":"J. Pharm. Biomed. Anal."},{"key":"2026092812293749600_cit18","doi-asserted-by":"publisher","first-page":"116990","DOI":"10.1016\/j.foodres.2025.116990","article-title":"Comparative analysis\nof phenolic compounds and triterpenoid saponins in edible plant parts\nof Acanthopanax sessilflorus using UPLC-MS and multivariate\nanalyses","volume":"219","author":"Kwon","year":"2025","journal-title":"Food Res. Int."},{"key":"2026092812293749600_cit19","doi-asserted-by":"publisher","first-page":"107619","DOI":"10.1016\/j.bioorg.2024.107619","article-title":"Intriguing steroid\nglycosides for cancer therapy by suppressing the DNA damage response\nand mTOR\/S6K signaling pathways","volume":"151","author":"An","year":"2024","journal-title":"Bioorg. Chem."},{"key":"2026092812293749600_cit20","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.fitote.2010.01.016","article-title":"New cardenolides\nfrom the stem bark\nof Trewia nudiflora","volume":"81","author":"Shilpi","year":"2010","journal-title":"Fitoterapia"},{"key":"2026092812293749600_cit21","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1248\/cpb.44.1797","article-title":"10-Carboxyloganin,\nnormonoterpenoid gluosides and dinormonoterpenoid\nglucosides from the leaves of Cerbera manghas","volume":"44","author":"Abe","year":"1996","journal-title":"Chem. Pharm. 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J."},{"issue":"12","key":"2026092812293749600_cit23","doi-asserted-by":"publisher","first-page":"2783","DOI":"10.3390\/plants10122783","article-title":"Estrogens\nand androgens in plants: The last 20 years of studies","volume":"10","author":"Janeczko","year":"2021","journal-title":"Plants"},{"key":"2026092812293749600_cit24","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3390\/ddc2010005","article-title":"Testolactone:\nThe rise and fall of\na drug","volume":"2","author":"Savic","year":"2023","journal-title":"Drugs Drug Candidates"},{"key":"2026092812293749600_cit25","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1055\/s-2006-957789","article-title":"In vitro\nbiological activities of alkaloids from Cryptolepis sanguinolenta","volume":"62","author":"Cimanga","year":"1996","journal-title":"Planta\nMed."},{"key":"2026092812293749600_cit26","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1055\/s-0034-1382900","article-title":"Combined use of extract libraries and HPLC-based activity\nprofiling for lead discovery: potential, challenges, and practical\nconsiderations","volume":"80","author":"Potterat","year":"2014","journal-title":"Planta Med."},{"key":"2026092812293749600_cit27","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1055\/s-0033-1350646","article-title":"Cardenolides and\nbufadienolide glycosides from Kalanchoe tubiflora and evaluation of cytotoxicity","volume":"79","author":"Huang","year":"2013","journal-title":"Planta Med."},{"key":"2026092812293749600_cit28","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.jep.2016.08.022","article-title":"Apoptotic activities of cardenolide\nglycosides from Asclepias subulata","volume":"193","author":"Rasco\u0301n-Valenzuela","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"2026092812293749600_cit29","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s11010-016-2914-8","article-title":"Cytotoxic effects of\nthe cardenolide convallatoxin and its Na,K-ATPase regulation","volume":"428","author":"Schneider","year":"2017","journal-title":"Mol. Cell. Biochem."},{"key":"2026092812293749600_cit30","doi-asserted-by":"publisher","first-page":"611657","DOI":"10.3389\/fphar.2021.611657","article-title":"The cardenolide\nglycoside acovenoside\nA interferes with epidermal growth factor receptor trafficking in\nnon-small cell lung cancer cells","volume":"12","author":"Hafner","year":"2021","journal-title":"Front. Pharmacol."},{"key":"2026092812293749600_cit31","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/s41587-023-01690-2","article-title":"Integrative analysis of multimodal mass spectrometry\ndata in MZmine 3","volume":"41","author":"Schmid","year":"2023","journal-title":"Nat. Biotechnol."},{"key":"2026092812293749600_cit32","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.phytochem.2013.11.024","article-title":"Cardenolide\nglycosides from Elaeodendron australe var. integrifolium","volume":"98","author":"Butler","year":"2014","journal-title":"Phytochemistry"},{"key":"2026092812293749600_cit33","doi-asserted-by":"publisher","first-page":"114329","DOI":"10.1016\/j.phytochem.2024.114329","article-title":"Bufadienolides from Helleborus foetidus and their cytotoxic properties on MCF-7 breast cancer\ncells","volume":"230","author":"Potterat","year":"2025","journal-title":"Phytochemistry"},{"key":"2026092812293749600_cit34","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1038\/nbt.3597","article-title":"Sharing and community curation of mass spectrometry\ndata with global natural products social molecular networking","volume":"34","author":"Wang","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"2026092812293749600_cit35","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1038\/nbt.2377","article-title":"A cross-platform toolkit for mass spectrometry\nand proteomics","volume":"30","author":"Chambers","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"2026092812293749600_cit36","doi-asserted-by":"publisher","first-page":"2597","DOI":"10.1038\/s41596-024-00996-y","article-title":"Reproducible\nmass spectrometry data processing\nand compound annotation in MZmine 3","volume":"19","author":"Heuckeroth","year":"2024","journal-title":"Nat. Protoc."},{"key":"2026092812293749600_cit37","doi-asserted-by":"publisher","first-page":"13738","DOI":"10.1073\/pnas.1608041113","article-title":"Topic modeling for untargeted substructure exploration\nin metabolomics","volume":"113","author":"van der Hooft","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U. 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Mach.\nIntell."},{"key":"2026092812293749600_cit41","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models\nof biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome\nRes."},{"key":"2026092812293749600_cit42","doi-asserted-by":"publisher","first-page":"402","DOI":"10.3389\/fphar.2020.00402","article-title":"Immunosuppressive activity of Artemisia argyi extract and isolated compounds","volume":"11","author":"Zimmermann-Klemd","year":"2020","journal-title":"Front. Pharmacol."},{"key":"2026092812293749600_cit43","doi-asserted-by":"publisher","first-page":"104694","DOI":"10.1016\/j.fitote.2020.104694","article-title":"Boswellia carteri extract and 3-O-acetyl-alpha-boswellic\nacid suppress T cell function","volume":"146","author":"Zimmermann-Klemd","year":"2020","journal-title":"Fitoterapia"}],"container-title":["Journal of Natural Products"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jnatprod.6c00033","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jnprdf\/article-pdf\/89\/5\/1462\/68681757\/acs.jnatprod.6c00033.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jnprdf\/article-pdf\/89\/5\/1462\/68681757\/acs.jnatprod.6c00033.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:31:57Z","timestamp":1790613117000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jnprdf\/article\/89\/5\/1462\/5187125\/Comprehensive-Metabolite-Profile-and-Cytotoxic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,4,24]]},"published-print":{"date-parts":[[2026,5,22]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jnatprod.6c00033","relation":{},"ISSN":["0163-3864","1520-6025"],"issn-type":[{"value":"0163-3864","type":"print"},{"value":"1520-6025","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]}}}