槲皮素-3-O-丙基衍生物的合成及生物活性研究

槲皮素是具有丰富生物活性的黄酮类化合物，药理活性显著。本文以槲皮素为先导物，选择性对C环3位羟基进行修饰，以廉价的芦丁为原料，经苄基保护、Williamson成醚反应，再经Pd/C催化加氢脱苄基得到28个未见文献报道的槲皮素-3-O-丙基衍生物，其结构经¹H NMR、¹³C NMR、ESI-MS进行确证。采用MTT法考察了所合成化合物对人食管鳞癌（EC109）、人胃癌（HGC27）、人乳腺癌（MCF-7）、小鼠黑色素瘤（B16-F10）的增殖抑制作用。结果显示，通过化学方法对槲皮素结构进行修饰后，其体外抗肿瘤活性增强。其中，化合物F3(IC₅₀=5.23±0.37μmol/L)、F5(IC₅₀=2.63±0.09μmol/L)对小鼠黑色素瘤（B16-F10）抑制作用比5-氟尿嘧啶(IC₅₀=14.38±0.27μmol/L)好，值得进一步研究。

Synthesis and Biological Activity of Quercetin-3-O-Propyl Derivatives

Quercetin is a flavonoid compound with rich biological activity and is a very promising phytochemical. In this paper, quercetin was used as the leader to selectively modify the hydroxyl group at the 3-position of the C ring. Using cheap rutin as raw material, selective protection of benzyl group, Williamson ether formation reaction, and Pd/C catalyzed hydrogenation and debenzylation to obtain 28 quercetin-3-O-propyl derivatives, none of them According to literature reports, the structure of the target product was confirmed by 1H NMR, 13C NMR, and ESI-MS. MTT method was used to investigate the effects of 28 quercetin-3-O-propyl derivatives on human esophageal squamous cell carcinoma (EC109), human gastric cancer (HGC27), human breast cancer (MCF-7), mouse melanoma (B16- F10) the proliferation inhibitory effect. The results showed that after structural modification of quercetin by chemical methods, its anti-tumor activity in vitro was enhanced. Among them, the inhibitory effect of compound F3 (5.229±0.371) and F7 (2.628±0.087) on mouse melanoma (B16-F10) is better than 5-fluorouracil (5-FU) (14.376±0.272), which is worthy of further study. The broth dilution method was used to evaluate the antibacterial activity of the synthesized compounds, and the MIC value was measured to determine the antibacterial ability of a certain drug in a constant amount. The antibacterial activity of most of the synthesized compounds is stronger than that of quercetin, but compared with the marketed drug levofloxacin, the activity is much lower, and the antibacterial activity is generally not good.