槲皮素-3-O-酰基酯的合成及抗肿瘤活性研究

Synthesis and Anticancer Activity of 3-O-Acyl Quercetin

目的合成槲皮素-3-O-酰基酯,探索抗肿瘤活性。方法以芦丁为原料,经苄基化保护、酸水解、酯化反应,再经钯/碳(Pd/C)催化加氢脱苄基得到12种槲皮素-3-O-酰基酯,使用红外(IR)、氢谱(^(1)H-NMR)、碳谱(C-NMR)、液质联用(ESI-MS)测定结构,采用邻二氮菲法和1,1-二苯-2-苦基肼(DPPH)法考察了12种目标化合物的抗氧化活性,采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)法测定抗肿瘤活性。结果光谱确定了目标化合物的结构,抗氧化性实验显示,大部分目标化合物的清除率(SC_(50))小于槲皮素或与槲皮素相当,提示3-OH不是槲皮素抗氧化活性的必需基团,目标化合物对人食管癌细胞EC109、人食管鳞癌细胞EC9706、人胃癌细胞MGC-803、人前列腺癌细胞PC-3四株肿瘤细胞的体外增殖抑制作用增强。结论合成了12个目标化合物,与母体槲皮素比较,对肿瘤细胞的增殖抑制作用显著增强。

OBJECTIVE To synthesize quercetin-3-O-acyl ester and explore the antitumor activity.METHODS Using cheap rutin as the raw material,twelve kinds of quercetin-3-O-acyl esters were obtained by benzylation protection,acid hydrolysis,esterification reaction,and then catalytic hydrogenation and debenzylation by Pd/C.Then,infrared(IR),hydrogen spectrum(^(1)H-NMR),carbon spectrum(C-NMR),and liquid chromatography-mass spectrometry(ESI-MS)were used to determine the structure.Meanwhile,the antioxidant activities of the twelve target compounds were investigated by o-phenanthroline method and 1,1-diphenyl-2-picrylhydrazyl(DPPH)method,and the antitumor activities were determined by 3-(4,5-dimethylthiazol-2)-2,5-diphenyltetrazolium bromide(MTT)method.RESULTS The structure of the target compounds was determined by spectroscopic analysis,and the results of antioxidant activity showed that the SC_(50)of the most target compounds was less than or equal to quercetin,which suggested that 3-OH is not an essential group for the antioxidant activity of quercetin,and the proliferation inhibition of the target compounds on human esophageal cancer cell EC109,human esophageal squamous cell carcinoma EC9706,human gastric cancer cell MGC-803 and human prostate cancer cell PC-3 in vitro was enhanced.CONCLUSION Twelve target compounds are synthesized and their inhibitory effects on tumor cell proliferation are significantly enhanced compared with quercetin.