{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T02:52:17Z","timestamp":1780368737289,"version":"3.54.1"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005363","name":"University of Buenos Aires","doi-asserted-by":"crossref","award":["UBACYT 20020220400220BA"],"award-info":[{"award-number":["UBACYT 20020220400220BA"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005363","name":"University of Buenos Aires","doi-asserted-by":"crossref","award":["20020220300118BA"],"award-info":[{"award-number":["20020220300118BA"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Agency for Science and Technology Promotion","award":["PICT-2019-00736"],"award-info":[{"award-number":["PICT-2019-00736"]}]},{"name":"National Agency for Science and Technology Promotion","award":["PICT-2021-0051"],"award-info":[{"award-number":["PICT-2021-0051"]}]},{"name":"National Agency for Science and Technology Promotion","award":["PICTO-2021-0018"],"award-info":[{"award-number":["PICTO-2021-0018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, highlighting the need to identify novel bioactive compounds with antitumor potential. Natural products constitute a valuable source of molecules with anticancer activity. In this study, we performed a comparative analysis of two classes of natural compounds\u2014sesquiterpene lactones (achillin and polymatin A) and naphthoquinones (\u03b1, \u03b2-lapachone and lapachol)\u2014in human PDAC cell lines on cell proliferation, metabolic activity and cell death induction and early mitochondrial alterations. Achillin showed limited antiproliferative, metabolic, and cytotoxic activity, whereas polymatin A exhibited activity in the micromolar range, yielding LC50 values of 16.11 \u00b1 2.27 \u03bcM and 20.00 \u00b1 1.90 \u03bcM for PANC-1 and MIAPaCa-2 cells, respectively. The naphtoquinones \u03b1- and \u03b2-lapachone effectively inhibited proliferation and metabolic activity and triggered cell death in both PDAC cell lines, with \u03b2-lapachone consistently displaying the highest activity with an LC50 of 4.00 \u00b1 0.07 \u03bcM for PANC-1 cells and 3.89 \u00b1 0.50 \u03bcM for MIAPaCa-2. Interestingly, achillin, polymatin A, \u03b1- and \u03b2-lapachone selectively induced cell death while sparing PBMCs. In contrast, lapachol showed weak activity, failing to achieve 50% inhibition or cell death within the tested concentration range and lacking tumor selectivity. Mechanistically, quinone derivatives promoted early mitochondrial superoxide modulation and membrane depolarization, consistent with a redox-active profile, whereas sesquiterpene lactones induced mitochondrial depolarization with limited mitochondrial superoxide overproduction, suggesting a distinct bioenergetic disruption phenotype. Overall, these findings highlight structure\u2013activity relationships among natural compounds and support further investigation of achillin, polymatin A and \u03b1,\u03b2-lapachone as promising molecular scaffolds in PDAC research.<\/jats:p>","DOI":"10.3390\/molecules31061014","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T11:14:14Z","timestamp":1773832454000},"page":"1014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In Vitro Evaluation of Natural Sesquiterpene Lactones and Naphthoquinones Against Pancreatic Ductal Adenocarcinoma Cells"],"prefix":"10.3390","volume":"31","author":[{"given":"Nadia T.","family":"Mirakian","sequence":"first","affiliation":[{"name":"CONICET\u2014Universidad de Buenos Aires, Instituto de Qu\u00edmica y Metabolismo del F\u00e1rmaco (IQUIMEFA), Ciudad Aut\u00f3noma de Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rub\u00e9n F.","family":"I\u00e1cono","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, C\u00e1tedra de Inmunolog\u00eda, Ciudad Aut\u00f3noma de Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana B.","family":"Pulido","sequence":"additional","affiliation":[{"name":"CONICET\u2014Universidad de Buenos Aires, Instituto de Estudios de la Inmunidad Humoral (IDEHU), Ciudad Aut\u00f3noma de Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4769-6570","authenticated-orcid":false,"given":"Mat\u00edas A.","family":"Pibuel","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, C\u00e1tedra de Inmunolog\u00eda, Ciudad Aut\u00f3noma de Buenos Aires C1113AAD, Argentina"},{"name":"CONICET\u2014Universidad de Buenos Aires, Instituto de Estudios de la Inmunidad Humoral (IDEHU), Ciudad Aut\u00f3noma de Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvina L.","family":"Lompard\u00eda","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, C\u00e1tedra de Inmunolog\u00eda, Ciudad Aut\u00f3noma de Buenos Aires C1113AAD, Argentina"},{"name":"CONICET\u2014Universidad de Buenos Aires, Instituto de Estudios de la Inmunidad Humoral (IDEHU), Ciudad Aut\u00f3noma de Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura C.","family":"Laurella","sequence":"additional","affiliation":[{"name":"CONICET\u2014Universidad de Buenos Aires, Instituto de Qu\u00edmica y Metabolismo del F\u00e1rmaco (IQUIMEFA), Ciudad Aut\u00f3noma de Buenos Aires C1113AAD, Argentina"},{"name":"Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, C\u00e1tedra de Farmacognosia, Ciudad Aut\u00f3noma de Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7348-7976","authenticated-orcid":false,"given":"Nicol\u00e1s","family":"P\u00e9rez-Mauad","sequence":"additional","affiliation":[{"name":"CONICET\u2014Universidad de Buenos Aires, Instituto de Qu\u00edmica y Metabolismo del F\u00e1rmaco (IQUIMEFA), Ciudad Aut\u00f3noma de Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7409-5303","authenticated-orcid":false,"given":"Cesar A. N.","family":"Catal\u00e1n","sequence":"additional","affiliation":[{"name":"Facultad de Bioqu\u00edmica, Qu\u00edmica y Farmacia, Instituto de Qu\u00edmica Org\u00e1nica, Universidad Nacional de Tucum\u00e1n, San Miguel de Tucum\u00e1n, Tucum\u00e1n T4000INI, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1s","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, C\u00e1tedra de Inmunolog\u00eda, Ciudad Aut\u00f3noma de Buenos Aires C1113AAD, Argentina"},{"name":"CONICET\u2014Universidad de Buenos Aires, Instituto de Estudios de la Inmunidad Humoral (IDEHU), Ciudad Aut\u00f3noma de Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9080-2108","authenticated-orcid":false,"given":"Mart\u00edn M.","family":"Ledesma","sequence":"additional","affiliation":[{"name":"Unidad de Conocimiento Traslacional, Hospital de Alta Complejidad del Bicentenario Esteban Echeverr\u00eda, Monte Grande B1842DOL, Argentina"},{"name":"CONICET\u2014Hospital de Alta Complejidad del Bicentenario Esteban Echeverr\u00eda, Centro de Investigaciones en Biomedicina Traslacional CIBiMeT, Monte Grande B1842DOL, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Carlucci","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, Departamento de Tecnolog\u00eda Farmac\u00e9utica, Instituto de Tecnolog\u00eda Farmac\u00e9utica u Biofarmacia (InTecFYB, UBA), Ciudad Aut\u00f3noma de Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9322-5748","authenticated-orcid":false,"given":"Valeria P.","family":"S\u00fclsen","sequence":"additional","affiliation":[{"name":"CONICET\u2014Universidad de Buenos Aires, Instituto de Qu\u00edmica y Metabolismo del F\u00e1rmaco (IQUIMEFA), Ciudad Aut\u00f3noma de Buenos Aires C1113AAD, Argentina"},{"name":"Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, C\u00e1tedra de Farmacognosia, Ciudad Aut\u00f3noma de Buenos Aires C1113AAD, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela L.","family":"Papademetrio","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, C\u00e1tedra de Inmunolog\u00eda, Ciudad Aut\u00f3noma de Buenos Aires C1113AAD, Argentina"},{"name":"Unidad de Conocimiento Traslacional, Hospital de Alta Complejidad del Bicentenario Esteban Echeverr\u00eda, Monte Grande B1842DOL, Argentina"},{"name":"CONICET\u2014Hospital de Alta Complejidad del Bicentenario Esteban Echeverr\u00eda, Centro de Investigaciones en Biomedicina Traslacional CIBiMeT, Monte Grande B1842DOL, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Cancer Statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1136\/gut.2006.103333","article-title":"Biology and management of pancreatic cancer","volume":"84","author":"Ghaneh","year":"2007","journal-title":"Postgrad. Med. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3747\/co.25.3708","article-title":"Towards an optimal treatment algorithm for metastatic pancreatic ductal adenocarcinoma (PDA)","volume":"25","author":"Uccello","year":"2018","journal-title":"Curr. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Desam, N.R., and Al-Rajab, A.J. (2022). Herbal biomolecules: Anticancer agents. Herbal Biomolecules in Healthcare, Academic Press.","DOI":"10.1016\/B978-0-323-85852-6.00001-9"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"S\u00fclsen, V., and Martino, V. (2018). Antiproliferative and cytotoxic activities. Sesquiterpene Lactones. Advances in Their Chemistry and Biological Aspects, Springer.","DOI":"10.1007\/978-3-319-78274-4"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Bailly, C. (2021). Anticancer Targets and Signaling Pathways Activated by Britannin and Related Pseudoguaianolide Sesquiterpene Lactones. Biomedicines, 9.","DOI":"10.3390\/biomedicines9101325"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Cutter, L.R., Ren, A.R., and Banerjee, I.A. (2025). Advances in Naturally and Synthetically Derived Bioactive Sesquiterpenes and Their Derivatives: Applications in Targeting Cancer and Neurodegenerative Diseases. Molecules, 30.","DOI":"10.3390\/molecules30214302"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Laurella, L.C., Mirakian, N.T., Garc\u00eda, M.N., Grasso, D.H., S\u00fclsen, V.P., and Papademetrio, D.L. (2022). Sesquiterpene Lactones as Promising Candidates for Cancer Therapy: Focus on Pancreatic Cancer. Molecules, 27.","DOI":"10.3390\/molecules27113492"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Beer, M.F., Bivona, A.E., S\u00e1nchez Alberti, A., Cerny, N., Reta, G.F., Mart\u00edn, V.S., Padr\u00f3n, J.M., Malchiodi, E.L., S\u00fclsen, V.P., and Donadel, O.J. (2019). Preparation of Sesquiterpene Lactone Derivatives: Cytotoxic Activity and Selectivity of Action. Molecules, 24.","DOI":"10.3390\/molecules24061113"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/j.tiv.2015.06.011","article-title":"Sesquiterpene lactones from Ambrosia spp. are active against a murine lymphoma cell line by inducing apoptosis and cell cycle arrest","volume":"29","author":"Martino","year":"2015","journal-title":"Toxicol. Vitr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.2174\/1389557520666200818212020","article-title":"Naphthoquinone Derivatives Isolated from Plants: Recent Advances in Biological Activity","volume":"20","author":"Ahmadi","year":"2020","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1080\/13543776.2017.1339792","article-title":"Lapachol and lapachone analogs: A journey of two decades of patent research(1997\u20132016)","volume":"27","author":"Hussain","year":"2017","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2008.10.004","article-title":"Red Lapacho (Tabebuia impetiginosa)\u2014A global ethnopharmacological commodity?","volume":"121","author":"Castellanos","year":"2009","journal-title":"J. Ethnopharmacol."},{"key":"ref_14","first-page":"13","article-title":"Research advances in natural sesquiterpene lactones: Overcoming cancer drug resistance through modulation of key signaling pathways","volume":"8","author":"Teng","year":"2025","journal-title":"Cancer drug Resist."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4355","DOI":"10.2174\/1381612825666190119114323","article-title":"Recent Advances on Cytotoxic Sesquiterpene Lactones","volume":"24","author":"Quintana","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2174\/1568011053765976","article-title":"Anti-cancer potential of sesquiterpene lactones: Bioactivity and molecular mechanisms","volume":"5","author":"Zhang","year":"2005","journal-title":"Curr. Med. Chem. Anticancer. Agents"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"116249","DOI":"10.1016\/j.ejmech.2024.116249","article-title":"Unlocking the potential of 1,4-naphthoquinones: A comprehensive review of their anticancer properties","volume":"268","author":"Plano","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"110397","DOI":"10.1016\/j.cbi.2023.110397","article-title":"Redox cycling of quinones reduced by ascorbic acid","volume":"373","author":"Njus","year":"2023","journal-title":"Chem. Biol. Interact."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"18203","DOI":"10.1074\/jbc.M117.813923","article-title":"The NQO1 bioactivatable drug, \u03b2-lapachone, alters the redox state of NQO1+ pancreatic cancer cells, causing perturbation in central carbon metabolism","volume":"292","author":"Silvers","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Pinho, B.R., Sousa, C., Valent\u00e3o, P., and Andrade, P.B. (2011). Is nitric oxide decrease observed with naphthoquinones in LPS stimulated RAW 264.7 macrophages a beneficial property?. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024098"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sanchez-Carranza, J.N., Gonz\u00e1lez-Maya, L., Razo-Hern\u00e1ndez, R.S., Salas-Vidal, E., Nolasco-Quintana, N.Y., Clemente-Soto, A.F., Garc\u00eda-Arizmendi, L., S\u00e1nchez-Ramos, M., Marquina, S., and Alvarez, L. (2019). Achillin Increases Chemosensitivity to Paclitaxel, Overcoming Resistance and Enhancing Apoptosis in Human Hepatocellular Carcinoma Cell Line Resistant to Paclitaxel (Hep3B\/PTX). Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11100512"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12929-015-0127-1","article-title":"Shikonin selectively induces apoptosis in human prostate cancer cells through the endoplasmic reticulum stress and mitochondrial apoptotic pathway","volume":"22","author":"Gara","year":"2015","journal-title":"J. Biomed. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"109955","DOI":"10.1016\/j.biopha.2020.109955","article-title":"Antitumor activity and mechanism of costunolide and dehydrocostus lactone: Two natural sesquiterpene lactones from the Asteraceae family","volume":"125","author":"Li","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1002\/jps.2600770217","article-title":"Inhibition of nucleic acid synthesis in p-388 lymphocytic leukemia tumor cells by helenalin and bis(helenalinyl)malonate in vivo","volume":"77","author":"Williams","year":"1988","journal-title":"J. Pharm. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bosco, A., and Golsteyn, R.M. (2017). Emerging Anti-Mitotic Activities and Other Bioactivities of Sesquiterpene Compounds upon Human Cells. Molecules, 22.","DOI":"10.3390\/molecules22030459"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"17066","DOI":"10.1038\/srep17066","article-title":"Tumor-selective use of DNA base excision repair inhibition in pancreatic cancer using the NQO1 bioactivatable drug, \u03b2-lapachone","volume":"5","author":"Chakrabarti","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.phytochem.2015.06.020","article-title":"The sesquiterpene lactone polymatin B from Smallanthus sonchifolius induces different cell death mechanisms in three cancer cell lines","volume":"117","author":"Ulloa","year":"2015","journal-title":"Phytochemistry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"20210","DOI":"10.1038\/s41598-020-76850-4","article-title":"DNA damage induced by KP372-1 hyperactivates PARP1 and enhances lethality of pancreatic cancer cells with PARP inhibition","volume":"10","author":"Viera","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s002800000221","article-title":"Novel mechanism of cellular DNA topoisomerase II inhibition by the pyranonaphthoquinone derivatives alpha-lapachone and beta-lapachone","volume":"47","author":"Krishnan","year":"2001","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1038\/s41598-017-02937-0","article-title":"\u03b2-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers","volume":"7","author":"Yang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Babu, M.S., Mahanta, S., Lakhter, A.J., Hato, T., Paul, S., and Naidu, S.R. (2018). Lapachol inhibits glycolysis in cancer cells by targeting pyruvate kinase M2. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191419"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mancini, I., Vigna, J., Sighel, D., and Defant, A. (2022). Hybrid Molecules Containing Naphthoquinone and Quinolinedione Scaffolds as Antineoplastic Agents. Molecules, 27.","DOI":"10.3390\/molecules27154948"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"112962","DOI":"10.1016\/j.ejmech.2020.112962","article-title":"A comprehensive review on \u03b2-lapachone: Mechanisms, structural modifications, and therapeutic potentials","volume":"210","author":"Gong","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2363000","DOI":"10.1080\/2162402X.2024.2363000","article-title":"\u03b2-Lapachone promotes the recruitment and polarization of tumor-associated neutrophils (TANs) toward an antitumor (N1) phenotype in NQO1-positive cancers","volume":"13","author":"Tumbath","year":"2024","journal-title":"Oncoimmunology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s40170-015-0137-1","article-title":"Targeting glutamine metabolism sensitizes pancreatic cancer to PARP-driven metabolic catastrophe induced by \u00df-lapachone","volume":"3","author":"Chakrabarti","year":"2015","journal-title":"Cancer Metab."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"S\u00fclsen, V.P., and Martino, V.S. (2018). Overview. Sesquiterpene Lactones: Advances in Their Chemistry and Biological Aspects, Springer International Publishing.","DOI":"10.1007\/978-3-319-78274-4_1"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Matos, M.S., Anast\u00e1cio, J.D., and Santos, C.N.D. (2021). Sesquiterpene Lactones: Promising Natural Compounds to Fight Inflammation. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13070991"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e13710","DOI":"10.1111\/jfbc.13710","article-title":"Reprogramming of erythrocyte lifespan by NF\u03baB-TNF\u03b1 naphthoquinone antagonist \u03b2-lapachone is regulated by calcium overload and CK1\u03b1","volume":"45","author":"Alfhili","year":"2021","journal-title":"J. Food Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"110936","DOI":"10.1016\/j.biopha.2020.110936","article-title":"Enhanced antitumor efficacy of lapachol-loaded nanoemulsion in breast cancer tumor model","volume":"133","author":"Miranda","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1080\/23818107.2021.1956585","article-title":"Morphoanatomy, histochemistry, essential oil, and other secondary metabolites of Artemisia copa (Asteraceae)","volume":"168","author":"Mercado","year":"2021","journal-title":"Bot. Lett."},{"key":"ref_41","first-page":"238","article-title":"Chemical composition and antioxidant activity of essential oil and extracts from Artemisia copa","volume":"6","author":"Marcial","year":"2007","journal-title":"Bolet\u00edn Latinoam. Caribe Plantas Med. Aromat."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s00049-016-0213-1","article-title":"Intraspecific variation of sesquiterpene lactones associated to a latitudinal gradient in Smallanthus macroscyphus (Heliantheae: Asteraceae)","volume":"26","author":"Mercado","year":"2016","journal-title":"Chemoecology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/S0305-1978(03)00064-4","article-title":"Melampolides from Smallanthus macroscyphus","volume":"31","author":"Cuenca","year":"2003","journal-title":"Biochem. Syst. Ecol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/6\/1014\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T08:03:04Z","timestamp":1774339384000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/6\/1014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":43,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["molecules31061014"],"URL":"https:\/\/doi.org\/10.3390\/molecules31061014","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]}}}