{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:07:13Z","timestamp":1790795233884,"version":"4.1.0"},"reference-count":80,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Centaurea is a genus compromising over 250 herbaceous flowering species and is used traditionally to treat several ailments. Among the Egyptian Centaurea species, C. lipii was reported to be cytotoxic against multidrug-resistant cancer cells. In this context, we aimed to explore the metabolome of C. lipii and compare it to other members of the genus in pursuance of identifying its bioactive principles. An LC-MS\/MS analysis approach synchronized with feature-based molecular networks was adopted to offer a holistic overview of the metabolome diversity of the Egyptian Centaurea species. The studied plants included C. alexandrina, C. calcitrapa, C. eryngioides, C. glomerata, C. lipii, C. pallescens, C. pumilio, and C. scoparia. Their constitutive metabolome showed diverse chemical classes such as cinnamic acids, sesquiterpene lactones, flavonoids, and lignans. Linking the recorded metabolome to the previously reported cytotoxicity identified sesquiterpene lactones as the major contributors to this activity. To confirm our findings, bioassay-guided fractionation of C. lipii was adopted and led to the isolation of the sesquiterpene lactone cynaropicrin with an IC50 of 1.817 \u00b5M against the CCRF-CEM leukemia cell line. The adopted methodology highlighted the uniqueness of the constitutive metabolome of C. lipii and determined the sesquiterpene lactones to be the responsible cytotoxic metabolites.<\/jats:p>","DOI":"10.3390\/molecules28020674","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T01:57:48Z","timestamp":1673315868000},"page":"674","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Feature-Based Molecular Networking for the Exploration of the Metabolome Diversity of Common Egyptian Centaurea Species in Relation to Their Cytotoxic Activity"],"prefix":"10.3390","volume":"28","author":[{"given":"Eman H.","family":"Reda","sequence":"first","affiliation":[{"name":"Phytochemistry Laboratory, National Organization for Drug Control and Research, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4085-5938","authenticated-orcid":false,"given":"Nesrine M.","family":"Hegazi","sequence":"additional","affiliation":[{"name":"Phytochemistry and Plant Systematics Department, National Research Centre, Dokki, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3176-1470","authenticated-orcid":false,"given":"Mona","family":"Marzouk","sequence":"additional","affiliation":[{"name":"Phytochemistry and Plant Systematics Department, National Research Centre, Dokki, Cairo 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8395-3629","authenticated-orcid":false,"given":"Zienab T. Abdel","family":"Shakour","sequence":"additional","affiliation":[{"name":"Phytochemistry Laboratory, National Organization for Drug Control and Research, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5864-1674","authenticated-orcid":false,"given":"Ali M.","family":"El-Halawany","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El-Sayeda A.","family":"El-Kashoury","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1639-3518","authenticated-orcid":false,"given":"Tarik A.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4819-2040","authenticated-orcid":false,"given":"Mahmoud A. A.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia 61519, Egypt"},{"name":"School of Health Sciences, University of Kwa-Zulu-Natal, Westville, Durban 4000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled A.","family":"Shams","sequence":"additional","affiliation":[{"name":"Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8650-6859","authenticated-orcid":false,"given":"Nahla S.","family":"Abdel-Azim","sequence":"additional","affiliation":[{"name":"Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Kampf","sequence":"additional","affiliation":[{"name":"Department for Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2637-1681","authenticated-orcid":false,"given":"Thomas","family":"Efferth","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences Chemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1644-723X","authenticated-orcid":false,"given":"Paul. W.","family":"Par\u00e9","sequence":"additional","affiliation":[{"name":"Department of Chemistry & Biochemistry, Texas Tech University, Lubbock, TX 79409, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0343-4969","authenticated-orcid":false,"given":"Mohamed-Elamir F.","family":"Hegazy","sequence":"additional","affiliation":[{"name":"Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1006\/anbo.2000.1364","article-title":"Generic delimitation and phylogeny of the subtribe Centaureinae (Asteraceae): A combined nuclear and chloroplast DNA analysis","volume":"87","author":"Susanna","year":"2001","journal-title":"Ann. Bot."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/B978-0-12-817901-7.00012-5","article-title":"Phytochemistry and biological activities of algerian Centaurea and related genera","volume":"63","author":"Ayad","year":"2019","journal-title":"Stud. Nat. Prod. Chem."},{"key":"ref_3","first-page":"149","article-title":"The biological activity of Centaurea L. species","volume":"17","author":"Reyhan","year":"2004","journal-title":"Gazi Univ. J. Sci."},{"key":"ref_4","first-page":"5587938","article-title":"A review on antidiabetic activity of Centaurea spp.: A new approach for developing herbal remedies","volume":"2021","author":"Hojjatifard","year":"2021","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1002\/ptr.4754","article-title":"Anti-inflammatory Activities of Eleven Centaurea Species Occurring in the Carpathian Basin","volume":"27","author":"Csupor","year":"2013","journal-title":"Phytother. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"134650","DOI":"10.1016\/j.foodchem.2022.134650","article-title":"Chemometric discrimination of Hylocereus undulatus from different geographical origins via their metabolic profiling and antidiabetic activity","volume":"404","author":"Younis","year":"2023","journal-title":"Food Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"20151","DOI":"10.1039\/D1RA02486H","article-title":"Two novel oxetane containing lignans and a new megastigmane from Paronychia arabica and in silico analysis of them as prospective SARS-CoV-2 inhibitors","volume":"11","author":"Elshamy","year":"2021","journal-title":"RSC Adv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"153409","DOI":"10.1016\/j.phymed.2020.153409","article-title":"2\u03b1-Hydroxyalantolactone from Pulicaria undulata: Activity against multidrug-resistant tumor cells and modes of action","volume":"81","author":"Hegazy","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"152771","DOI":"10.1016\/j.phymed.2018.11.031","article-title":"Cytotoxicity of 40 Egyptian plant extracts targeting mechanisms of drug-resistant cancer cells","volume":"59","author":"Hegazy","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ernst, M., Kang, K.B., Caraballo-Rodr\u00edguez, A.M., Nothias, L.-F., Wandy, J., Chen, C., Wang, M., Rogers, S., Medema, M.H., and Dorrestein, P.C. (2019). MolNetEnhancer: Enhanced molecular networks by integrating metabolome mining and annotation tools. Metabolites, 9.","DOI":"10.1101\/654459"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"840","DOI":"10.3109\/13880209.2010.551538","article-title":"Secondary metabolites of Centaurea calolepis and evaluation of cnicin for anti-inflammatory, antioxidant, and cytotoxic activities","volume":"49","author":"Erel","year":"2011","journal-title":"Pharm. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3527","DOI":"10.1016\/0031-9422(92)83721-A","article-title":"Sesquiterpene lactones and lignans from Centaurea species","volume":"31","author":"Marco","year":"1992","journal-title":"Phytochemistry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1002\/hlca.200900126","article-title":"Sesquiterpene Lactones from Daucus Glaber","volume":"93","author":"Sallam","year":"2010","journal-title":"Helv. Chim. Acta"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Salachna, P., Pietrak, A., and \u0141opusiewicz, \u0141.J.M. (2021). Antioxidant Potential of Flower Extracts from Centaurea spp. Depends on Their Content of Phenolics, Flavonoids and Free Amino Acids. Molecules, 26.","DOI":"10.3390\/molecules26247465"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Reda, E.H., Shakour, Z.T.A., El-Halawany, A.M., El-Kashoury, E.-S.A., Shams, K.A., Mohamed, T.A., Saleh, I., Elshamy, A.I., Atia, M.A., and El-Beih, A.A. (2021). Comparative Study on the Essential Oils from Five Wild Egyptian Centaurea Species: Effective Extraction Techniques, Antimicrobial Activity and In-Silico Analyses. Antibiotics, 10.","DOI":"10.3390\/antibiotics10030252"},{"key":"ref_16","first-page":"568","article-title":"Determination of dibenzylbutyrolactone-type lignans in Centraurea species and analysis of arctigenin\u2019s anticancer effect","volume":"76","author":"Szokol","year":"2010","journal-title":"Planta Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1080\/19440049.2021.1902575","article-title":"High resolution mass spectrometry workflow for the analysis of food contaminants: Application to plant toxins, mycotoxins and phytoestrogens in plant-based ingredients","volume":"38","author":"Bessaire","year":"2021","journal-title":"Food Addit. Contam."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/B978-0-12-819487-4.00017-3","article-title":"Recent patents on sesquiterpene lactones with therapeutic application","volume":"Volume 69","author":"Elso","year":"2021","journal-title":"Studies in Natural Products Chemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1021\/jm00294a001","article-title":"Tumor inhibitors. 69. Structure-cytotoxicity relations among the sesquiterpene lactones","volume":"14","author":"Kupchan","year":"1971","journal-title":"J. Med. Chem."},{"key":"ref_20","first-page":"577","article-title":"Toxic activities of sesquiterpene lactones: Structural and biochemical aspects","volume":"3","author":"Schmidt","year":"1999","journal-title":"Curr. Org. Chem"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Akbar, S. (2020). Centaurea behen L.(Asteraceae\/Compositae). Handbook of 200 Medicinal Plants, Springer.","DOI":"10.1007\/978-3-030-16807-0"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"56","DOI":"10.3889\/oamjms.2022.7232","article-title":"Chartolepis intermedia Boiss. and Centaurea ruthenica Lam.\u2013New Medicina Plants Containing Pharmacologically Active Compounds","volume":"10","author":"Mukhametzhanova","year":"2022","journal-title":"Open Access Maced. J. Med. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.fitote.2017.05.016","article-title":"Antiproliferative activity against leukemia cells of sesquiterpene lactones from the Turkish endemic plant Centaurea drabifolia subsp. detonsa","volume":"120","author":"Formisano","year":"2017","journal-title":"Fitoterapia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1002\/ptr.6906","article-title":"Inhibitory effects of cynaropicrin on human melanoma progression by targeting MAPK, NF-\u03baB, and Nrf-2 signaling pathways in vitro","volume":"35","author":"Ercolano","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lu, X., Saeed, M.E.M., Hegazy, M.-E.F., Kampf, C.J., and Efferth, T. (2020). Chemopreventive property of Sencha tea extracts towards sensitive and multidrug-resistant leukemia and multiple myeloma cells. Biomolecules, 10.","DOI":"10.3390\/biom10071000"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Pluskal, T., Castillo, S., Villar-Briones, A., and Ore\u0161i\u010d, M. (2010). MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC Bioinform., 11.","DOI":"10.1186\/1471-2105-11-395"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/nbt.3597","article-title":"Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking","volume":"34","author":"Wang","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13321-016-0116-8","article-title":"Fragmentation trees reloaded","volume":"8","year":"2016","journal-title":"J. Cheminform."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"36754","DOI":"10.1038\/srep36754","article-title":"Genomic and transcriptomic profiling of resistant CEM\/ADR-5000 and sensitive CCRF-CEM leukaemia cells for unravelling the full complexity of multi-factorial multidrug resistance","volume":"6","author":"Kadioglu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1002\/ijc.27675","article-title":"High-throughput SNP-based authentication of human cell lines","volume":"132","author":"Castro","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1021\/np070252e","article-title":"Sesquiterpene lactones from Staehelina fruticosa","volume":"71","author":"Kotsos","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Tastan, P., Hajd\u00fa, Z., K\u00fasz, N., Zupk\u00f3, I., Sinka, I., Kivcak, B., and Hohmann, J. (2019). Sesquiterpene lactones and flavonoids from Psephellus pyrrhoblepharus with antiproliferative activity on human gynecological cancer cell lines. Molecules, 24.","DOI":"10.3390\/molecules24173165"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2298\/JSC100127008C","article-title":"Antimicrobial activity of secondary metabolites isolated from Centaurea spruneri Boiss. & Heldr","volume":"76","author":"Karioti","year":"2011","journal-title":"J. Serb. Chem. Soc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1021\/np058042u","article-title":"Sesquiterpene Lactones from Centaurea spinosa and their antibacterial and cytotoxic activities","volume":"68","author":"Saroglou","year":"2005","journal-title":"J. Nat. Prod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1021\/np070125i","article-title":"Minor sesquiterpene lactones from Centaurea pullata and their antimicrobial activity","volume":"70","author":"Djeddi","year":"2007","journal-title":"J. Nat. Prod."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/0031-9422(95)00569-2","article-title":"An artemisinic acid analogue from Tithonia diversifolia","volume":"41","author":"Bordoloi","year":"1996","journal-title":"Phytochemistry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.phytol.2011.08.002","article-title":"Flavonol glycosides from Chenopodium foliosum Asch","volume":"4","author":"Nikolov","year":"2011","journal-title":"Phytochem. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/S0031-9422(00)00254-5","article-title":"Sesquiterpene lactones from Centaurea thessala and Centaurea attica. Antifungal activity","volume":"55","author":"Skaltsa","year":"2000","journal-title":"Phytochemistry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1021\/np0700570","article-title":"Cytotoxic germacranolides and acyclic diterpenoides from the seeds of Carpesium triste","volume":"70","author":"Gao","year":"2007","journal-title":"J. Nat. Prod."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/S0305-1978(02)00055-8","article-title":"Secondary constituents from Centaurea horrida and their evolutionary meaning","volume":"30","author":"Flamini","year":"2002","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/S0305-1978(02)00219-3","article-title":"Flavonoids from Centaurea furfuracea (Asteraceae)","volume":"31","author":"Akkal","year":"2003","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_42","first-page":"281","article-title":"Guaianolides from the aerial parts of Centaurea hololeuca","volume":"1","author":"Rosselli","year":"2006","journal-title":"Nat. Prod. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1007\/s10600-014-0886-z","article-title":"Flavonoids and biological activities of Centaurea stenolepis","volume":"50","author":"Sen","year":"2014","journal-title":"Chem. Nat. Compd."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/BF00564262","article-title":"Luteolin glycosides in some plants of the family Compositae","volume":"6","author":"Bandyukova","year":"1970","journal-title":"Chem. Nat. Compd."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ahmed, S.A., and Kamel, E.M. (2014). Cytotoxic activities of flavonoids from Centaurea scoparia. Sci. World J., 2014.","DOI":"10.1155\/2014\/274207"},{"key":"ref_46","first-page":"285","article-title":"Secondary Metabolites of Centaurea Cyanus L","volume":"37","author":"Erel","year":"2007","journal-title":"Ank. \u00dcniversitesi Eczac\u0131l\u0131k Fak\u00fcltesi Derg."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1021\/acs.jafc.6b05136","article-title":"Identification and quantification of potential anti-inflammatory hydroxycinnamic acid amides from wolfberry","volume":"65","author":"Wang","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1080\/14786419.2016.1226823","article-title":"Lignans and indole alkaloids from the seeds of Centaurea vlachorum Hartvig (Asteraceae), growing wild in Albania and their biological activity","volume":"31","author":"Hodaj","year":"2017","journal-title":"Nat. Prod. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"10717","DOI":"10.3390\/ijms221910717","article-title":"Liquid-Liquid Chromatography Separation of Guaiane-Type Sesquiterpene Lactones from Ferula penninervis Regel & Schmalh. and Evaluation of Their In Vitro Cytotoxic and Melanin Inhibitory Potential","volume":"22","author":"Luca","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0031-9422(00)94776-9","article-title":"Sesquiterpene lactones from Centaurea hermannii","volume":"35","author":"Serin","year":"1994","journal-title":"Phytochemistry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.fitote.2018.12.001","article-title":"Amino acid-sesquiterpene lactone conjugates from the aerial parts of Centaurea pungens and evaluation of their antimicrobial activity","volume":"133","author":"Labed","year":"2019","journal-title":"Fitoterapia"},{"key":"ref_52","first-page":"57","article-title":"Flavonoid O-heterosides from flowers of Centaurea solstitialis L (Compositae)","volume":"17","author":"Kamanzi","year":"1983","journal-title":"Plantes Med. Et Phytother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1007\/s12272-013-0070-1","article-title":"Phenolic constituents from Parakmeria yunnanensis and their anti-HIV-1 activity","volume":"36","author":"Shang","year":"2013","journal-title":"Arch. Pharmacal Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1248\/cpb.53.1416","article-title":"Bioactive constituents from Chinese natural medicines. XV. Inhibitory effect on aldose reductase and structures of saussureosides A and B from Saussurea medusa","volume":"53","author":"Xie","year":"2005","journal-title":"Chem. Pharm. Bull."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/S0031-9422(01)00345-4","article-title":"A flavonoid sulphate and other compounds from the roots of Centaurea bracteata","volume":"58","author":"Flamini","year":"2001","journal-title":"Phytochemistry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.phytochem.2013.02.005","article-title":"Sesquiterpene lactones from Lactuca canadensis and their chemotaxonomic significance","volume":"90","author":"Michalska","year":"2013","journal-title":"Phytochemistry"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.bse.2005.07.019","article-title":"Yellow flavonoids in Centaurea ruthenica as flower pigments","volume":"2","author":"Mishio","year":"2006","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1016\/j.carres.2010.09.002","article-title":"Phenolic glycosides with antiproteasomal activity from Centaurea urvillei DC. subsp. urvillei","volume":"345","author":"Karaalp","year":"2010","journal-title":"Carbohydr. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3070","DOI":"10.1080\/14786419.2018.1517343","article-title":"Centaurea microcarpa Coss. & Dur.(Asteraceae) extracts: New cyanogenic glucoside and other constituents","volume":"33","author":"Baatouche","year":"2019","journal-title":"Nat. Prod. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1021\/acs.jnatprod.8b01004","article-title":"Cytotoxic germacrane-type sesquiterpene lactones from the whole plant of Carpesium lipskyi","volume":"82","author":"Zhu","year":"2019","journal-title":"J. Nat. Prod."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1021\/np050480d","article-title":"Hepatoprotective Sesquiterpene Glycosides from Sarcandra g labra","volume":"69","author":"Li","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1016\/S0040-4039(00)81732-3","article-title":"Structural determination of clementein, a new guaianolide isolated from Centaurea clementei","volume":"24","author":"Massanet","year":"1983","journal-title":"Tetrahedron Lett."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/jccs.202000156","article-title":"Cytotoxic and chemotaxonomic study of isolated metabolites from Centaurea aegyptiaca","volume":"68","author":"Mohamed","year":"2021","journal-title":"J. Chin. Chem. Soc."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1021\/np300292f","article-title":"3-Hydroxy-3-methylglutaryl flavonol glycosides from Oxytropis falcata","volume":"75","author":"Wang","year":"2012","journal-title":"J. Nat. Prod."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1080\/14786419.2010.534995","article-title":"A new flavonoid and other constituents from Centaurea nicaeensis All. var. walliana M","volume":"26","author":"Hammoud","year":"2012","journal-title":"Nat. Prod. Res."},{"key":"ref_66","first-page":"468","article-title":"Flavonoids from Centaurea sinaica","volume":"63","author":"Kamel","year":"1992","journal-title":"Fitoterapia"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Olennikov, D.N., Chirikova, N.K., Kashchenko, N.I., Gornostai, T.Y.G., Selyutina, I.Y., and Zilfikarov, I.N. (2017). Effect of low temperature cultivation on the phytochemical profile and bioactivity of Arctic plants: A case of Dracocephalum palmatum. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122579"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s10600-013-0759-x","article-title":"New isorhamnetin glycosides and other phenolic compounds from Calendula officinalis","volume":"49","author":"Olennikov","year":"2013","journal-title":"Chem. Nat. Compd."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Menet, J.-M., and Thiebaut, D. (1999). Countercurrent Chromatography, CRC Press.","DOI":"10.1201\/9781482273809"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.sajb.2019.11.021","article-title":"Phytochemical composition and antioxidant, cytotoxic and anti-inflammatory properties of Psephellus goeksunensis (Ayta\u00e7 & H. Duman) Greuter & Raab-Straube","volume":"130","author":"Demiroz","year":"2020","journal-title":"South Afr. J. Bot."},{"key":"ref_71","first-page":"61","article-title":"Chemical investigation of Centaurea glomerata vahl","volume":"6","author":"Zaghloul","year":"1990","journal-title":"Mansoura J. Pharm. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.phytol.2009.03.002","article-title":"A flavonoid with cytotoxic activity and other constituents from Centaurea africana","volume":"2","author":"Seghiri","year":"2009","journal-title":"Phytochem. Lett."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S0031-9422(01)00066-8","article-title":"Two flavonoids and other compounds from the aerial parts of Centaurea bracteata from Italy","volume":"57","author":"Flamini","year":"2001","journal-title":"Phytochemistry"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1007\/s10600-015-1404-7","article-title":"Flavonoids of the exudate of Centaurea calcitrapa","volume":"51","author":"Kitouni","year":"2015","journal-title":"Chem. Nat. Compd."},{"key":"ref_75","first-page":"403","article-title":"Phytochemical studies on the leaves of Vitex negundo L. (Lagundi), 1: Investigations of the bronchial relaxing constituents [Philippines]","volume":"116","author":"Dayrit","year":"1987","journal-title":"Philipp. J. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Radan, M., Carev, I., Te\u0161evi\u0107, V., Politeo, O., and \u010culi\u0107, V.\u010c. (2017). Qualitative HPLC-DAD\/ESI-TOF-MS Analysis, Cytotoxic, and Apoptotic Effects of Croatian Endemic Centaurea ragusina L. Aqueous Extracts. Chem. Biodivers., 14.","DOI":"10.1002\/cbdv.201700099"},{"key":"ref_77","first-page":"479","article-title":"In vitro antihepatocellular carcinoma activity of secondary metabolites of Centaurea kilaea Boiss","volume":"24","year":"2020","journal-title":"J. Res. Pharm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1016\/0031-9422(82)85199-6","article-title":"Eudesmanolides and kaurene derivatives from Wedelia hookeriana","volume":"21","author":"Bohlmann","year":"1982","journal-title":"Phytochemistry"},{"key":"ref_79","first-page":"498","article-title":"Isolation of chemical constituents of Centaurea virgata lam. and xanthine oxidase inhibitory activity of the plant extract and compounds","volume":"13","author":"Hajdu","year":"2017","journal-title":"Med. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"371","DOI":"10.4314\/tjpr.v19i2.20","article-title":"Phytochemical analysis and bioactivity screening of three medicinal plants of Saudi Arabia","volume":"19","author":"Mahmood","year":"2020","journal-title":"Trop. J. Pharm. Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/2\/674\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:04:47Z","timestamp":1760119487000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/2\/674"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,9]]},"references-count":80,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["molecules28020674"],"URL":"https:\/\/doi.org\/10.3390\/molecules28020674","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,9]]}}}