氯硝柳胺衍生物的合成及抗肿瘤活性研究

Synthesis and biological evaluation of niclosamide derivatives as antitumor agents

以氯硝柳胺为起始原料,经醚化、亲核取代反应得到目标化合物,采用MTT法考察所合成化合物对人类乳腺癌细胞(MDA-MB-231)和人类胰腺癌细胞(ASPC-1)的体外抗肿瘤活性。合成了5个氯硝柳胺衍生物,其结构均经IR、1H-NMR、13C-NMR和MS确证。初步的体外抗肿瘤活性结果显示目标化合物9b和9c的抗肿瘤活性强于阳性对照药,其中化合物9b的活性对所测两种肿瘤株的抑制活性均强于阳性对照药,展现出较强的应用前景。

The target compounds were synthesized from niclosamide by etherification and nucleophilic substitution reaction.The antitumor activity in vitro of these compounds have been studied by MTT assay with human breast cancer cells（MDA-MB-231） and human pancreatic cells（ASPC-1）.Five new compounds were synthesized,and the chemical structures were characterized by IR,1HNMR,13C-NMR and MS.Preliminary anti-tumor activity in vitro results showed that compound 9a-9d for inhibitory activity of tumor cell lines by differences,compounds 9b and 9c had stronger cell growth inhibitory action than the positive control drug,showing strong prospect.