Key Laboratory of Cluster Science, Ministry of Education of China, Beijing Key Laboratory of Photoelectronic; Electrophotonic Conversion Materials, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China.
J Med Chem. 2022 Jul 14;65(13):9174-9192. doi: 10.1021/acs.jmedchem.2c00380. Epub 2022 Jun 24.
We designed a novel series of bifunctional inhibitors of α-glucosidase and aldose reductase (ALR2) based on the structure of hydroxychalcone. The two enzymes relate to blood glucose level and anomalously elevated polyol pathway of glucose metabolism under hyperglycemia, respectively. Most compounds in the series exhibited a potent inhibitory activity for both enzymes, and a significant antioxidant property was shown. Further studies of and using streptozotocin (STZ)-induced diabetic rats as a model found that achieved not only good antihyperglycemic and glucose tolerance effect in a dose-dependent manner ( < 0.01) but also showed effective inhibition of polyol pathway. significantly suppressed the maltose-induced postprandial glucose elevation. Additionally, they effectively improved lipid metabolisms and restored an antioxidant ability. Therefore, the two compounds may be promising agents for the prevention and treatment of diabetic complications.
我们设计了一系列基于查尔酮结构的新型α-葡萄糖苷酶和醛糖还原酶（ALR2）双功能抑制剂。这两种酶分别与血糖水平和高血糖下葡萄糖代谢的异常升高的多元醇途径有关。该系列中的大多数化合物对两种酶均表现出很强的抑制活性，同时还显示出显著的抗氧化特性。进一步研究和 发现，使用链脲佐菌素（STZ）诱导的糖尿病大鼠作为模型，不仅实现了剂量依赖性的良好降血糖和葡萄糖耐量作用（<0.01），而且还显示出对多元醇途径的有效抑制。显著抑制了麦芽糖诱导的餐后血糖升高。此外，它们还能有效改善脂代谢并恢复抗氧化能力。因此，这两种化合物可能是预防和治疗糖尿病并发症的有前途的药物。
