Syntheses, neural protective activities, and inhibition of glycogen synthase kinase-3β of substituted quinolines
作者:Jianyu Lu、Izumi Maezawa、Sahani Weerasekara、Ramazan Erenler、Tuyen D.T. Nguyen、James Nguyen、Luxi Z. Swisher、Jun Li、Lee-Way Jin、Alok Ranjan、Sanjay K. Srivastava、Duy H. Hua
DOI:10.1016/j.bmcl.2014.05.085
日期:2014.8
A new series of fifteen 5-, 6-, and 8-appended 4-methylquinolines were synthesized and evaluated for their neural protective activities. Selected compounds were further examined for their inhibition of glycogen synthase kinase-3β (GSK-3β) and protein kinase C (PKC). Two most potent analogs, compounds 3 and 10, show nanomolar protective activities in amyloid β-induced MC65 cells and enzymatic inhibitory
合成了一个新系列的 15 种 5-、6-和 8-附加 4-甲基喹啉,并评估了它们的神经保护活性。进一步检查所选化合物对糖原合酶激酶-3β (GSK-3β) 和蛋白激酶 C (PKC) 的抑制作用。两种最有效的类似物,化合物3和10,在淀粉样蛋白 β 诱导的 MC65 细胞中显示出纳摩尔级的保护活性和对 GSK-3β 的酶抑制活性,但对 PKC 的抑制活性较差。使用正常小鼠模型,分布最有力的模拟3在各种组织中进行了可能的运动毒性作用和肝转氨酶活性的抑制。没有发现运动活性的明显下降和肝转氨酶的抑制。该化合物在阿尔茨海默病小鼠模型中长期使用似乎是安全的。