槲皮素衍生物的合成及其生物活性研究

Studies on the Synthesis and Biological Activities of Quercetin Derivatives

槲皮素是一种优良的天然抗氧化剂。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,经苄基选择性保护、Williamson成醚反应,再经Pd/C催化加氢脱苄基得到5个槲皮素酰胺类衍生物,均未见文献报道,目标产物结构经IR、1H NMR、13C NMR、ESI-MS确证。采用DPPH法考察了5个目标化合物的抗氧化活性,结果显示,大部分目标化合物的SC50小于槲皮素或与槲皮素相当,这表明3-OH不是槲皮素抗氧化活性的必需基团。采用MTT法考察了5个槲皮素酰胺类衍生物对人食管鳞癌细胞EC109、人食管鳞癌细胞EC9706、人胃癌细胞SGC7901及小鼠黑色素瘤细胞B16-F10的增殖抑制作用。结果显示,通过化学方法对槲皮素进行结构修饰后,其体外抗肿瘤活性增强。其中,化合物7-1对SGC7901的抑制作用(IC50=67.228μmol/L)明显优于母药槲皮素(IC50=91.115μmol/L)和5-FU(IC50=78.236μmol/L),是一个很有潜力的新型抗肿瘤候选化合物。

The quercetin is a kind of excellent natural antioxidant.The quercetin is used as a precursor and the OH on 3-C of C ring is modified selectively.Five kinds of quercetin derivatives are synthesized with low-cost rutin as the raw material by the reactions of selective benzyl protection,the Williamson reaction and then by catalytic hydrogenation with Pd/C,removing benzyl.All the new synthesized compounds have not been reported before,and the chemical structures are identified by IR,1 H-NMR,13 C-NMR and ESI-MS spectra.Furthermore,the antioxidant activity of all the synthesized compounds is determined by the DPPH method.The results show that the SC50 of most target compounds is less than or equal to quercetin which indicates the OH on 3-C is not a necessary group for antioxidant activity of quercetin.In addition,the proliferation-inhibition effect of the five kinds of quercetin derivatives on four types of cancer cells such as human esophageal squamous cancer cells EC109,human esophageal squamous cancer cells EC9706,human gastric cancer cells SGC7901 and mouse melanoma cells B16-F10 is also evaluated.The results show that the anti-tu-mor activity in vitro of the chemically modified quercetin is significantly enhanced.Among these five new compounds,the inhibition effect(IC50=67.228μmol/L)of compound 7-1 obviously outperforms the technical concentrate quercetin(IC50=91.115μmol/L)and 5-FU(IC50=78.236μmol/L),which is expected to become a new potential anti-tumor candidate.