粉防己碱衍生物的合成及其抗肿瘤作用研究

Synthesis and Bioactivities Investigation of Tetrandrine Derivatives as Anti-cancer Agents

以粉防己碱为原料,依次经硝化、还原和Chan-Lam-Evans偶联共计3步反应,设计并合成了12种双苄基异喹啉衍生物,其结构经^(1)H NMR、^(13)C NMR和HR-MS表征。采用MTT法对所得衍生物对人肝癌细胞HepG2、人正常肝细胞HL7702、人肺癌细胞A549的体外抑制活性进行了初步评价。MTT实验结果表明:所得衍生物对癌细胞生长具有较强的抑制作用,并对其构效关系进行了初步评价。化合物7、8对两种癌细胞均有良好的抗肿瘤活性,可能作为一种潜在的抗肝癌药物。其中化合物7对HepG2细胞的抑制作用最强,IC_(50)值为3.72μmol·L^(-1),并具有明显的抑制HepG2迁移和侵袭的能力。

Twelve dibenzyl isoquinoline derivatives were synthesized from tetrandrine by nitrification,reduction and Chan-Lam-Evans coupling reaction.Their structures were confirmed by ^(1)H NMR,^(13)C NMR and HR-MS.These derivatives were used to evaluate the anticancer activity of HepG2,HL7702 and A549 in vitro.The results of in vitro cytotoxicity test showed that these derivatives had strong inhibitory effect on the growth of cancer cells,and the structure-activity relationship of these derivatives was evaluated by MTT assay.Compounds 7 and 8 showed good antitumor activity against both kinds of cancer cells,among which compound 7 showed the strongest antitumor activity against HepG2 cells with IC_(50) value of 3.72μmol·L^(-1).Compound 7 could significantly inhibit the migration and invasion of HepG2 cells,and the results suggested that compound 7,8 might be a potential anti-tumor drug.