胡椒碱衍生物的合成及其抗肿瘤活性研究

Synthesis and antitumor activity evaluation of piperine derivatives

目的设计并合成新型具有抗肿瘤活性的胡椒碱衍生物,并评价其体外抗肿瘤活性。方法以天然产物胡椒碱为起始原料,与不同的氨基化合物进行缩合反应,合成系列胡椒碱氨基衍生物。采用体外MTT法测定目标化合物对人乳腺癌细胞MCF-7和人肝癌细胞HepG2的抑制活性。结果与结论合成了30个胡椒碱系列衍生物,其中27个为未见文献报道的新化合物。目标化合物的结构经核磁共振氢谱和电喷雾质谱(ESI-MS)确证。体外抗肿瘤活性实验结果显示,大多数胡椒碱衍生物对人乳腺癌细胞MCF-7和人肝癌细胞HepG2具有较好的抑制作用,其中2-氨基噻唑衍生物对两种肿瘤细胞的抑制活性较为明显,而且5位取代化合物对于人乳腺癌细胞MCF-7的抑制活性优于4位取代的化合物。

Piperine has been reported to have various bioactivity,especially antitumor activity.Some studies have showed that bioavailability and pharmacological properties could be improved by structural modification.Therefore 30 amide derivatives of piperine were synthesized via condensation reaction.Among them,27 compounds were not reported in literature.The structures of these compounds were confirmed by^1H-NMR and ESI-MS.The inhibitory activity of piperine and its derivatives against human breast adenocarcinoma cell line(MCF-7)and human hepatocarcinoma cell line(HepG2)were evaluated by MTT test.The results showed that most target compounds possessed more potent antitumor activities.Among them,2-aminothiazole derivatives possessed better antitumor activities of both MCF-7 and HepG2.In addition,the 5-substituent structures showed better antitumor activities against MCF-7 than 4-substituent structures of 2-aminothiazole derivatives.