{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T21:39:54Z","timestamp":1782941994616,"version":"3.54.5"},"reference-count":37,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Leading Research Groups support project from the subsidy increased for the period 2020\u20132025","award":["Art. 387 (3) of the Law of 20 July 2018 on Higher Education and Science, obtained in 2019"],"award-info":[{"award-number":["Art. 387 (3) of the Law of 20 July 2018 on Higher Education and Science, obtained in 2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: The study investigated four flavanone-derived \u03b3-oxa-\u03b5-lactones: a parent unsubstituted compound and its three derivatives with the methoxy group in positions 2\u2032, 4\u2032 and 8. Our objective was to find out if the introduction of the methoxy group into the aromatic ring affects in vitro anti-tumor potency of the investigated lactones. Methods: Cytotoxic and pro-apoptotic effects were assessed with cytometric tests with propidium iodide, annexin V, and Western blot techniques. We also investigated potential synergistic potency of the tested lactones and glucocorticoids in canine lymphoma\/leukemia cell lines. Results: The tested flavanone-derived lactones showed anti-cancer activity in vitro. Depending on its location, the methoxy group either increased or decreased cytotoxicity of the derivatives as compared with the parent compound. The most potent lactone was the one with the methoxy group at position 4\u2032 of the B ring (compound 3), and the weakest activity was observed when the group was located at C-8 in the A ring. A combination of the lactones with glucocorticoids confirmed their synergy in anti-tumor activity in vitro. Conclusions: Methoxy-substituted flavanone-derived lactones effectively kill canine lymphoma\/leukemia cells in vitro and, thanks to their synergistic action with glucocorticoids, may potentially be applied in the treatment of hematopoietic cancers.<\/jats:p>","DOI":"10.3390\/molecules26206295","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T22:52:47Z","timestamp":1634683967000},"page":"6295","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Methoxy-Substituted \u03b3-Oxa-\u03b5-Lactones Derived from Flavanones\u2014Comparison of Their Anti-Tumor Activity In Vitro"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7449-1661","authenticated-orcid":false,"given":"Aleksandra","family":"Pawlak","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Wroc\u0142aw University of Environmental and Life Sciences, C.K. Norwida 31, 50-375 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9725-7969","authenticated-orcid":false,"given":"Marta","family":"Henklewska","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Wroc\u0142aw University of Environmental and Life Sciences, C.K. Norwida 31, 50-375 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5377-6609","authenticated-orcid":false,"given":"Beatriz","family":"Hern\u00e1ndez-Su\u00e1rez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Wroc\u0142aw University of Environmental and Life Sciences, C.K. Norwida 31, 50-375 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Siepka","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Wroc\u0142aw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3271-779X","authenticated-orcid":false,"given":"Witold","family":"G\u0142adkowski","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Wroc\u0142aw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Czes\u0142aw","family":"Wawrze\u0144czyk","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Wroc\u0142aw University of Environmental and Life Sciences, Norwida 25, 50-375 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Motykiewicz-Pers","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Wroc\u0142aw University of Environmental and Life Sciences, C.K. Norwida 31, 50-375 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo\u017cena","family":"Obmi\u0144ska-Mrukowicz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Wroc\u0142aw University of Environmental and Life Sciences, C.K. Norwida 31, 50-375 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10414","DOI":"10.1016\/j.tet.2013.09.094","article-title":"Synthesis and anticancer activity of novel halolactones with \u03b2-aryl substituents from simple aromatic aldehydes","volume":"69","author":"Skrobiszewski","year":"2013","journal-title":"Tetrahedron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/toxsci\/kfp097","article-title":"Chiral toxicology: It\u2019s the same thing...only different","volume":"110","author":"Smith","year":"2009","journal-title":"Toxicol. Sci. Off. J. Soc. 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