13-酰胺基取代苦参碱衍生物的合成及抗肿瘤活性研究

Synthesis and antitumor activity of 13-acylmatrine derivatives

目的合成13-酰胺基取代苦参碱衍生物及研究该类化合物的体外抗肿瘤活性。方法以槐果碱为原料,通过迈克尔加成(Michael addition),叠氮还原酰化反应,制得系列13-位酰胺取代的衍生物,所有化合物结构均经1 H NMR等谱确证;选取人肝癌细胞(BEL-7404)和小鼠黑色素瘤细胞(K111)对所合成的目标化合物进行体外抗肿瘤药理活性筛选。结果设计合成了9个新化合物,大多数化合物对两株肿瘤细胞都具有较强的抑制活性。结论化合物4b和4e对人肝癌细胞(BEL-7404)有较强的抑制活性。

Objective To synthesize a series of 13-acylmatrine derivatives and evaluate their in vitro antitumor activity, Methods Using sophocarpine as the starting material,a series of new compounds were synthesized through Michael addition, Staudinger reduction and acylation. The structure of target compounds were confirmed by 1 H NMR and MS techniques. Their ailtitumor activity against human hepatoma cells（BEL-7404） and mice melanoma cells （Klll） were evaluated in vitro by MTT assay. Results We synthesized 9 compounds and all the compounds exhibited inhibitory activities against BEL-7404 and Kill. Conclusion Compound 4b and compound 4e exhibit good in vitro antitumor activity to human hepatoma cells （BEL-7404）.