目的 设计合成以槲皮素为母核,引入基团为烯丙基或异戊烯基的系列槲皮素衍生物,并对其进行体外抗肿瘤活性研究。方法 以槲皮素(化合物1)为起始物,通过成醚反应合成目标化合物2、3、4、5、6、7、8。分别以人肺癌细胞A549、人乳腺癌细胞MDA-MB-231、人肝癌细胞HepG2为靶细胞,采用MTT法对所合成的化合物进行体外抗肿瘤活性评价。结果 合成了两个烯丙基取代、5个异戊烯基取代的槲皮素衍生物,其中5个为新化合物(4,5,6,7,8),其结构经1H-NMR、13C-NMR表征。部分化合物对所选肿瘤细胞的增殖有较强的抑制作用:其中化合物6对肿瘤细胞A549、MDA-MB-231和HepG2均具有较显著的抗增殖活性,IC50值分别为15.23、16.56、12.32 μmol·L-1;化合物7对肿瘤细胞A549、MDA-MB-231具有较显著的抗增殖活性,IC50值分别为8.92、2.90 μmol·L-1。结论 槲皮素引入异戊烯基合成的化合物6和7具有显著的抗肿瘤活性,具有进一步研究的意义。
Abstract
OBJECTIVE To design and synthesize series of quercetin derivatives by introducing allyl or prenyl groups and investigate their antitumor activities in vitro.METHODS Compounds 2, 3, 4, 5, 6, 7 and 8 were synthesized with quercetin as starting material through the etherification reaction.The antitumor activities were evaluated by MTT assay against human lung cells (A549), human breast cancer cells (MDA-MB-231), and human hepatoma cells (HepG2).RESULTS Two allyl-substituted and five prenyl-substituted quercetin derivatives were synthesized. Compounds 4, 5, 6, 7, and 8 were new compounds, and their structures were characterized by 1H-NMR and 13C-NMR. Compounds 6 and 7 exhibited observable anti-proliferative activity. Compound 6 inhibited the growth of A549, MDA-MB-231, and HepG2 cells with IC50 values of 15.23, 16.56, and 12.32 μmol·L-1, respectively.Compound 7 restrained the growth of A549 and MDA-MB-231 cells with IC50 values of 8.92 and 2.90 μmol·L-1, respectively. CONCLUSION Compounds 6 and 7 synthesized by introducing prenyl groups into quercetin have significant anti-tumor activities, which are worth of further research.
关键词
槲皮素 /
烯丙基 /
异戊烯基 /
抗肿瘤活性
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Key words
quercetin /
allyl group /
prenyl group /
anti-tumor activity
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中图分类号：
R284
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参考文献
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