5,7-二羟基黄酮类似物的合成及抗糖尿病活性研究.docVIP

  Synthesis and antidiabetic activity of 5,7–dihydroxyflavonoids and analogues# 5 10 15 20 25 30 35 Qin Nan1, Chang Liushuan1, Li Chunbao2, Jin Meina1, Duan Hongquan1** (1. School of Pharmaceutical Sciences, Research Center of Basic Medical Sciences, Tianjin Medical University; 2. School of Science, Tianjin University) Abstract: Aim of the study: This is a study aiming to evaluate the structural elements essential to the antidiabetic activity of flavonoids. Methods: We synthesized two series of flavonoids, 5,7-dihydroxyflavanones and 5,7-dihydroxyflavones. Results: In a screening for in vitro potential antidiabetic activity, most of the flavonoids showed a remarkable in vitro activity, and compounds 5f, 7d, and 10c were significantly more effective than the positive control, metformin. Conclusion: The biological activity was mainly affected by introducing structural modification at the ring B moiety of the flavonoid skeleton. The results suggest that 5,7–dihydroxyflavonoids can be considered promising candidates in the development of new antidiabetic lead compounds. Key words: Flavonoids; 5,7-Dihydroxy; Antidiabetic activity 0 Introduction Diabetes mellitus is a metabolic alterations characterized by hyperglycemia resulting from defects in insulin secretion, action or both, currently affecting approximately 3% of the world population [1]. Noninsulin-dependent diabetes mellitus (type II diabetes, T2D) is a heterogeneous disease characterized by hyperglycemia, which is caused by a disorder of insulin secretion, insulin resistance (IR) in target tissues, and activation of the hepatic glucose production pathway in the liver [2,3]. The key treatment strategy is keeping patient blood glucose within normal levels. So far, several drugs have been developed to control T2D. They can be divided into the hypoglycemic (sulfonylureas) and anti-hyperglycemic ones (biguanides, α-glucosidase inhibitors, and thiazolidinediones). Because the mechanism of DM is quite complex, many