Design, synthesis and biological evaluation of thiazole- and indole-based derivatives for the treatment of type II diabetes

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• 作者：Qinyuan Xu ; Li Huang ; Juan Liu ; Liang Ma ; Tao Chen ; Jinying Chen ; Fei Peng ; Dong Cao ; Zhuang Yang ; Neng Qiu ; Jingxiang Qiu ; Guangcheng Wang ; Xiaolin Liang ; Aihua Peng ; Mingli Xiang ; Yuquan Wei ; Lijuan Chen ; ^{lijuan17@hotmail.com}
• 关键词：Ap2 ; Thiazole- and indole-based ; TNF-¦Á ; Diet-induced obesity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：June, 2012
• 年：2012
• 卷：52
• 期：Complete
• 页码：70-81
• 全文大小：3212 K

文摘

Present studies have shown that the lipid carrier has a significant role in several aspects of metabolic syndrome in A-FABP/ap2-deficient mice, including type 2 diabetes and atherosclerosis. 38 Thiazole- and indole-based derivatives were synthesized and investigated for their inhibitory effects on the production of LPS-stimulated TNF-¦Á. Among them, 12b exhibited an excellent inhibitory efficiency compared to BMS309403 (95 % vs. 85 % ) at the concentration of 10?¦ÌM and a binding affinity for ap2 with the apparent K_i values 33?nM. Oral administration of 12b at a dosage of 50?mg/kg effectively reduced the levels of plasma blood glucose, triglycerides, insulin, total cholesterol and alanine aminotransferase in high-fat/diet-induced obesity model. The results highlighted that 12b was a potent anti-diabetic agent.