Methoxy-Substituted γ-Oxa-ε-Lactones Derived from Flavanones—Comparison of Their Anti-Tumor Activity In Vitro
| Autor: | Marta Henklewska, Aleksandra Pawlak, Czesław Wawrzeńczyk, Monika Siepka, Karolina Motykiewicz-Pers, Witold Gładkowski, Bożena Obmińska-Mrukowicz, Beatriz Hernandez-Suarez |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Lymphoma
Stereochemistry Cell Survival flavanone-derived lactones Pharmaceutical Science Organic chemistry Antineoplastic Agents Apoptosis In Vitro Techniques Article Analytical Chemistry lactones chemistry.chemical_compound Structure-Activity Relationship Dogs QD241-441 Western blot Annexin Cell Line Tumor Drug Discovery medicine Potency Animals Propidium iodide Physical and Theoretical Chemistry Cytotoxicity chemistry.chemical_classification Leukemia medicine.diagnostic_test Molecular Structure Chemistry flavanones medicine.disease In vitro Chemistry (miscellaneous) anti-cancer activity Molecular Medicine Drug Screening Assays Antitumor Lactone |
| Zdroj: | Molecules, Vol 26, Iss 6295, p 6295 (2021) Molecules Volume 26 Issue 20 |
| ISSN: | 1420-3049 |
| Popis: | Background: The study investigated four flavanone-derived γ-oxa-ε-lactones: a parent unsubstituted compound and its three derivatives with the methoxy group in positions 2′, 4′ 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′ 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. |
| Databáze: | OpenAIRE |
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