To discover more derivatives with better glucose-lowering efficacy compared with berberine, twenty-three novel compounds with 4,7,12,12a-tetrahydro-5H-thieno[3′,2′:3,4]pyrido[1,2-b]isoquinoline or 5,8,12,12a-tetrahydro-6H-thieno[2′,3′:4,5]pyrido[2,1-a]isoquinoline cores were designed, synthesized, and biologically evaluated in vitro in continuation of our previous work on indirect activators of adenosine 5′-monophosphate-activated protein kinase (AMPK). Nine compounds effectively stimulated glucose consumption (>2.3-fold at 10 μM) in L6 myotube cells, and two compounds (4d and 4s) exhibited superior inhibitory activity (<57.6% at 5 μM) compared with berberine on gluconeogenesis in rat primary hepatocytes. Additionally, these compounds significantly up-regulated the phosphorylation of AMPK and its substrate, acetyl-CoA carboxylase (ACC) and slightly decreased the mitochondrial membrane potential in L6 myotube cells.

为了发现更多与小ber碱相比具有更好的降糖功效的衍生物，二十三个新颖的化合物具有4,7,12,12a-tetrahydro-5 H -thieno [3'，2'：3,4] pyrido [1,2 - b ]异喹啉或5,8,12,12a四氢-6- ħ -噻吩并[2'，3'：4,5]吡啶并[2,1-一个]异喹啉核设计，合成，和生物学评价在体外在我们先前关于间接激活腺苷5'-单磷酸激活蛋白激酶（AMPK）的工作的基础上。九种化合物有效刺激L6肌管细胞中的葡萄糖消耗（在10μM时> 2.3倍），而两种化合物（4d和4s）与黄连素相比，对小白鼠对大鼠原代肝细胞糖异生有更好的抑制活性（在5μM时<57.6％）。此外，这些化合物显着上调了AMPK及其底物，乙酰辅酶A羧化酶（ACC）的磷酸化，并略微降低了L6肌管细胞中的线粒体膜电位。