藜芦胺类似物的合成及体外抗肿瘤活性研究

Synthesis of Veratramine Analogs and Evaluation of Their Antiproliferative Activities on Cancer Cell in vitro

以黎芦属植物中含量丰富的甾体生物碱藜芦胺（Ⅰ）为原料,经结构修饰,共得到5种藜芦胺类似物Ⅱ~Ⅵ。经核磁共振谱、质谱确定化合物结构。以已知的Hedgehog信号通路抑制剂环巴胺为阳性对照,采用人胃癌细胞SGC-7901和人胰腺癌细胞Aspc-1进行体外抑制肿瘤细胞增殖活性筛选。结果表明,化合物Ⅳ、Ⅴ、Ⅵ的抑制肿瘤细胞增殖活性优于环巴胺。初步构效关系研究表明,在藜芦胺的哌啶环上引入烟酸及对硝基苯甲酰基团,可显著提高其抗肿瘤活性。

The steroidal alkaloid veratramine,which is rich in Veratrum plants,was taken as starting material for structure modification. Five veratramine analogs Ⅱ ~ Ⅵ were obtained. Their structures were determined by means of MS and NMR. Cyclopamine,the first inhibitor of Hedgehog signaling pathway,was used as the positive control,and the antiproliferative activities of yielded compounds on human gastric cancer cell SGC- 7901 and human pancreatic cancer cell Aspc- 1 in vitro were carried out. The results showed that the antiproliferative activities of compounds Ⅳ,Ⅴand Ⅵ were much more potent than that of cyclopamine. Preliminary study of the structure-activity relationship suggested that antiproliferative activities of veratramine analogs could be increased by introducing nicotinic acid and pnitrophenyl formyl groups at piperidine ring of veratramine.