Chrysin (5,7-dihydroxyflavone, 6) and galangin 3-methyl ether (5,7-dihydroxy-3-methoxy flavone, 7) were obtained from the leaves of Oroxylum indicum (L.) Kurz in 4% and 6% yields, respectively. Both compounds could act as pan-histone deacetylase (HDAC) inhibitors. Structural modification of these lead compounds provided thirty-eight derivatives which were further tested as HDAC inhibitors. Compounds 6b, 6c, and 6q were the most potent derivatives with the IC₅₀ values of 97.29 ± 0.63 μM, 91.71 ± 0.27 μM, and 96.87 ± 0.45 µM, respectively. Molecular docking study indicated the selectivity of these three compounds toward HDAC8 and the test against HDAC8 showed IC₅₀ values in the same micromolar range. All three compounds were further evaluated for the anti-proliferative activity against HeLa and A549 cell lines. Compound 6q exhibited the best activity against HeLa cell line with the IC₅₀ value of 13.91 ± 0.34 μM. Moreover, 6q was able to increase the acetylation level of histone H3. These promising HDAC inhibitors deserve investigation as chemotherapeutic agents for treating cancer.

Graphical abstract

中文翻译：

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木蝴蝶两种黄酮类化合物及其半合成衍生物作为组蛋白脱乙酰酶抑制剂的评价及分子对接研究

白杨素 (5,7-二羟基黄酮, 6 ) 和高良姜素 3-甲基醚 (5,7-二羟基-3-甲氧基黄酮, 7 ) 从Oroxylum indicum (L.) Kurz的叶子中获得，产率分别为 4% 和 6% ， 分别。这两种化合物都可以作为泛组蛋白脱乙酰酶 (HDAC) 抑制剂。这些先导化合物的结构修饰提供了 38 种衍生物，将其作为 HDAC 抑制剂进行了进一步测试。化合物6b、6c和6q是最有效的衍生物，IC ₅₀值分别为 97.29 ± 0.63 μM、91.71 ± 0.27 μM 和 96.87 ± 0.45 μM。分子对接研究表明这三种化合物对HDAC8具有选择性，针对HDAC8的测试显示IC ₅₀值在相同的微摩尔范围内。进一步评估了所有三种化合物对 HeLa 和 A549 细胞系的抗增殖活性。化合物6q对HeLa细胞系表现出最佳活性，IC ₅₀值为13.91 ± 0.34 μM。此外，6q能够增加组蛋白 H3 的乙酰化水平。这些有前途的 HDAC 抑制剂值得作为治疗癌症的化疗药物进行研究。

图形概要