含硫醚、硒醚及二硫键链接侧链的小檗碱衍生物的合成及体外抗肿瘤活性  

Syntheses and In vitro Antitumor Activities of Berberine Derivatives Containing Sulfide, Selenide and Disulfide Linked Side Chains

作　　者：李亚梅 刘传峰 孙驰宇 张大军[1] 栾天 Li Yamei;Liu Chuanfeng;Sun Chiyu;Zhang Dajun;Luan Tian(Department of Pharmacy,Shenyang Medical College,Shenyang,110034;Department of Pharmacy Jiangsu Food&Pharmaceutieal Science College,Huaian 223023)

机构地区：[1]沈阳医学院药学院,沈阳110034 [2]江苏食品药品职业技术学院药学院,淮安223023

出　　处：《化学通报》2022年第7期833-838,共6页Chemistry

基　　金：辽宁省科学技术计划项目(2020-MS-313);沈阳医学院博士科研启动基金项目(20205041)和沈阳医学院科学研究基金项目(20191027)资助。

摘　　要：为开发高效低毒的抗肿瘤天然产物衍生物,依据药物拼合原理设计并合成了10个新型小檗碱衍生物。将盐酸小檗碱与含单硫醚、单硒醚和二硫键脂肪链片段通过缩合反应得到目标化合物,其化学结构均经过核磁共振氢谱、碳谱以及高分辨质谱确证。采用噻唑蓝(MTT)法考察其体外抗肿瘤活性,结果表明,7个化合物针对不同的癌细胞株的抑制活性优于盐酸小檗碱,同时对人正常肝细胞L02的毒性较低。化合物3e的体外抗肿瘤活性最佳(针对BEL-7402的IC_(50)值为8.70μmol/L,选择性指数为3.61),可对其深入研究用以开发高效低毒的抗肿瘤药物。In order to develop efficient and low-toxic anti-tumor compounds, ten novel berberine derivatives were designed and synthesized based on the principle of pharmacochemical molecular combination. The target compounds were obtained by condensation reactions of berberine hydrochloride with different disulfide, thioether or selenium ether moieties, and their chemical structures were confirmed by ~1H NMR,C NMR, and high-resolution mass spectrometry. Their in vitro antitumor activities were investigated by thiazole blue(MTT) method. The results showed that the inhibitory activities of the seven compounds against different cancer cell lines were better than that of berberine hydrochloride, while their toxicities to human normal hepatocytes L02 were lower. Compound 3 e exhibits the best in vitro antitumor activity(IC_(50) value of 8.70 μmol/L and selectivity index of 3.61 against BEL-7402) and can be investigated in depth for the development of more efficient and less toxic antitumor drugs.

关 键 词：小檗碱 硫醚 硒醚 二硫键 

分 类 号：TQ460.1[化学工程—制药化工]