PDF(Pubmed)
Abstract：
Flavonoids, a class of natural compounds with anticancer activity, exhibit varying biological activities and potencies based on their structural differences. Acylation, including acetylation of flavonoids, generally increases their structural diversity, which is closely related to the diversity of bioactivity within this group of compounds. However, it remains largely unknown how acetylation affects the bioactivity of many flavonoids. Based on our previous findings that O-acetylation enhances quercetin\'s bioactivity against various cancer cells, we synthesized 12 acetylated flavonoids, including seven novel compounds, to investigate their anticancer activities in the MDA-MB-231, HCT-116, and HepG2 cell lines. Our results showed that acetylation notably enhanced the cell proliferation inhibitory effect of quercetin and kaempferol across all cancer cell lines tested. Interestingly, while the 5,7,4\'-O-triacetate apigenin (3Ac-A) did not show an enhanced the effect of inhibition of cell proliferation through acetylation, it exhibited significantly strong anti-migration activity in MDA-MB-231 cells. In contrast, the 7,4\'-O-diacetate apigenin (2Ac-Q), which lacks acetylation at the 5-position hydroxy group, showed enhanced cell proliferation inhibitory effect but had weaker anti-migration effects compared to 3Ac-A. These results indicated that acetylated flavonoids, especially quercetin, kaempferol, and apigenin derivatives, are promising for anticancer applications, with 3Ac-A potentially having unique anti-migration pathways independent of apoptosis induction. This study highlights the potential application of flavonoids in novel chemopreventive strategies for their anti-cancer activity.
摘要：
黄酮类化合物,一类具有抗癌活性的天然化合物，根据它们的结构差异，表现出不同的生物活性和效力。酰化,包括类黄酮的乙酰化，通常会增加它们的结构多样性，这与该组化合物中生物活性的多样性密切相关。然而,乙酰化如何影响许多黄酮类化合物的生物活性仍然是未知的。根据我们以前的发现，O-乙酰化增强槲皮素对各种癌细胞的生物活性，我们合成了12种乙酰化黄酮类化合物,包括七个新化合物，研究它们在MDA-MB-231，HCT-116和HepG2细胞系中的抗癌活性。我们的结果表明，乙酰化显着增强槲皮素和山奈酚在所有测试的癌细胞系中的细胞增殖抑制作用。有趣的是,而5,7,4'-O-三乙酸芹菜素（3Ac-A）没有显示出通过乙酰化抑制细胞增殖的增强作用，在MDA-MB-231细胞中表现出明显的抗迁移活性。相比之下,7,4'-O-二乙酸芹菜素（2Ac-Q），在5位羟基缺乏乙酰化，与3Ac-A相比，显示出增强的细胞增殖抑制作用，但具有较弱的抗迁移作用。这些结果表明，乙酰化类黄酮，尤其是槲皮素,山奈酚,和芹菜素衍生物，有希望用于抗癌应用，3Ac-A可能具有独立于细胞凋亡诱导的独特的抗迁移途径。这项研究强调了类黄酮在抗癌活性的新型化学预防策略中的潜在应用。
