9-取代小檗碱类似物的体外降糖活性研究  

Study on hypoglycemic activity of 9-substituted berberine derivatives in vitro

作　　者：任刚[1] 张明睿[2] 宋丹青[1] 蒋建东[1,3] 李迎红[1] 

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所,北京100050 [2]辽宁师范大学生命科学学院,辽宁大连116081 [3]中国医学科学院北京协和医学院药物研究所,北京100050

出　　处：《药学学报》2017年第8期1282-1286,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81302823);国家重大协同创新资助项目(2016-I2M-1-011)

摘　　要：本研究系统评价了20个9-取代小檗碱类似物的糖消耗活性,结果表明,在9位引入乙氧基有利于体外糖消耗活性的增加。9-乙氧小檗碱化合物2a在多个剂量水平下显示出高于阳性对照小檗碱的活性,在1.25μmol·L^(-1)剂量下,2a的活性达到小檗碱的5.4倍。同时,2a激活AMPK的活性是小檗碱的2.8倍。因此,化合物2a可成为进一步改造的母核。The glucose consumption activity of 9-substitued analogues of berberine was evaluated in L6 myotubes. It was found that the introduction of an ethoxy group on the 9-position of berberine was beneficial for the activity. 9-Ethoxy berberine analogue 2a exhibited superior activity to berberine in multiple dose levels, and the activity of 2a was 5.4 times as high as that of berberine at the dose of 1.25 μmol·L^（-1）. At the meantime, the potency on AMPK activation of 2a was 2.8 times of that of berberine at the dose of 10 μmol·L^（-1）. Therefore, the compound 2a is a promising scaffold for further modification.

关 键 词：小檗碱类似物 糖消耗 合成 

分 类 号：R914.5[医药卫生—药物化学]