A series of halogenated derivatives of natural flavonoids: baicalein and chrysin were designed and investigated as possible ligands for the catalytic subunit of tumor‐associated human kinase CK2. Thermal shift assay method, in silico modeling, and high‐performance liquid chromatography‐derived hydrophobicity together with IC50 values determined in biochemical assay were used to explain the ligand affinity to the catalytic subunit of human protein kinase CK2. Obtained results revealed that substitution of baicalein and chrysin with halogen atom increases their binding affinity to hCK2α, and for 8‐chlorochrysin the observed effect is even stronger than for the reference CK2 inhibitor—4,5,6,7‐tetrabromo‐1H‐benzotriazole. The cytotoxic activities of the baicalein and chrysin derivatives in the in vitro model have been evaluated for MV4‐11 (human biphenotypic B myelomonocytic leukemia), A549 (human lung adenocarcinoma), LoVo (human colon cancer), and MCF‐7 (human breast cancer) as well as on the nontumorigenic human breast epithelial MCF‐10A cell lines. Among the baicalein derivatives, the strongest cytotoxic effect was observed for 8‐bromobaicalein, which exhibited the highest activity against breast cancer cell line MCF‐7 (IC50 10 ± 3 μM). In the chrysin series, the strongest cytotoxic effect was observed for unsubstituted chrysin, which exhibited the highest activity against leukemic cell line MV4‐11 (IC50 10 ± 4 μM).

中文翻译：

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天然黄酮素、黄芩素和白杨素的卤化作用增强了它们对人蛋白激酶 CK2 的亲和力

一系列天然黄酮类化合物的卤化衍生物：黄芩素和白杨素被设计和研究作为肿瘤相关人激酶 CK2 催化亚基的可能配体。热位移分析方法、计算机模拟和高效液相色谱衍生的疏水性以及在生化分析中确定的 IC50 值被用来解释配体对人蛋白激酶 CK2 催化亚基的亲和力。获得的结果表明黄芩素和白杨素被卤素原子取代增加了它们对 hCK2α 的结合亲和力，并且对于 8-氯黄素观察到的效果甚至比参考 CK2 抑制剂 - 4,5,6,7-四溴-1H-苯并三唑更强. 黄芩素和白杨素衍生物在体外模型中对 MV4-11（人双表型 B 型骨髓单核细胞白血病）、A549（人肺腺癌）、LoVo（人结肠癌）和 MCF-7（人乳腺癌）的细胞毒活性进行了评估。癌症）以及非致瘤性人乳腺上皮 MCF-10A 细胞系。在黄芩素衍生物中，8-溴黄芩素的细胞毒作用最强，其对乳腺癌细胞系 MCF-7 的活性最高（IC50 10 ± 3 μM）。在白杨素系列中，观察到未取代白杨素的细胞毒性作用最强，其对白血病细胞系 MV4-11 表现出最高的活性（IC50 10 ± 4 μM）。和 MCF-7（人乳腺癌）以及非致瘤性人乳腺上皮 MCF-10A 细胞系。在黄芩素衍生物中，8-溴黄芩素的细胞毒作用最强，其对乳腺癌细胞系 MCF-7 的活性最高（IC50 10 ± 3 μM）。在白杨素系列中，观察到未取代白杨素的细胞毒性作用最强，其对白血病细胞系 MV4-11 表现出最高的活性（IC50 10 ± 4 μM）。和 MCF-7（人乳腺癌）以及非致瘤性人乳腺上皮 MCF-10A 细胞系。在黄芩素衍生物中，8-溴黄芩素的细胞毒作用最强，其对乳腺癌细胞系 MCF-7 的活性最高（IC50 10 ± 3 μM）。在白杨素系列中，观察到未取代白杨素的细胞毒性作用最强，其对白血病细胞系 MV4-11 表现出最高的活性（IC50 10 ± 4 μM）。