Synthesis and Biological Evaluation of 5-Benzylidenepyrimidine-2,4,6(1<i>H</i>,3<i>H</i>,5<i>H</i>)-trione Derivatives for the Treatment of Obesity-Related Nonalcoholic Fatty Liver Disease
作者:Liang Ma、Caifeng Xie、Yan Ran、Xiaolin Liang、Li Huang、Heying Pei、Jinying Chen、Juan Liu、Yun Sang、Huijun Lai、Aihua Peng、Mingli Xiang、Yuquan Wei、Lijuan Chen
DOI:10.1021/jm301164y
日期:2012.11.26
Nonalcoholic fatty liver disease (NAFLD), one of chronic liver diseases, seems to be rising as the obesity epidemic continues. In this study, 54 novel (thio)barbituric acid derivatives have been synthesized and evaluated for pharmacological activity. 7h exhibited potent glucose-lowering effects on insulin-resistant HepG2 cells and regulated adiponectin and leptin expression in 3T3-L1 adipocytes. Oral
非酒精性脂肪性肝病(NAFLD)是一种慢性肝病,随着肥胖病的流行,这种病似乎正在增加。在这项研究中,已经合成了54种新型(硫代)巴比妥酸衍生物,并对其药理活性进行了评估。7h对3D3-L1脂肪细胞中的胰岛素抵抗性HepG2细胞表现出有效的降糖作用,并调节脂联素和瘦素的表达。25 mg kg口服7h –1天–1持续4周可通过减少人体,肝脏和脂肪的重量以及调节空腹血糖,胰岛素,甘油三酸酯,LDL-c,ALT,脂联素和肝脏中的肝素含量来改善高脂饮食诱导的NAFLD的进展甘油三酸酯,总胆固醇。H&E染色显示7h阻止了NAFLD脂肪在肝脏中的沉积,并阻止了脂肪组织中脂肪细胞的数量和大小的增加。此外,用7h治疗可以减轻肥胖的临床症状,将血清生物标志物恢复到适当的范围,并改善OIOG和IGTT对DIO小鼠的葡萄糖耐量。