Department of Pharmacology and Toxicology, Wrocław University of Environmental and Life Sciences, C.K. Norwida 31, 50-375 Wrocław, Poland.
Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland.
Molecules. 2021 Oct 18;26(20):6295. doi: 10.3390/molecules26206295.
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.
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.
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 ), 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.
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.
本研究调查了四种黄烷酮衍生的γ-氧代-ε-内酰胺：一个未取代的母体化合物及其三个在 2'、4' 和 8 位带有甲氧基的衍生物。我们的目的是研究在芳环中引入甲氧基是否会影响所研究的内酰胺的体外抗肿瘤效力。
通过碘化丙啶、膜联蛋白 V 和 Western blot 技术的细胞计量检测评估细胞毒性和促凋亡作用。我们还研究了测试的内酰胺和糖皮质激素在犬淋巴瘤/白血病细胞系中的潜在协同作用。
测试的黄烷酮衍生内酰胺在体外表现出抗癌活性。根据其位置，甲氧基的存在或不存在会增加或降低衍生物的细胞毒性，与母体化合物相比。最有效的内酰胺是 B 环上 4'位带有甲氧基的内酰胺（化合物 ），而 A 环上 C-8 位带有甲氧基的内酰胺活性最弱。内酰胺与糖皮质激素的组合证实了它们在体外抗肿瘤活性中的协同作用。
甲氧基取代的黄烷酮衍生内酰胺可有效杀死犬淋巴瘤/白血病细胞体外，并且由于它们与糖皮质激素的协同作用，它们可能有潜力应用于造血系统癌症的治疗。
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